title: Barry Sanders

text: As a rookie in 1989, Sanders started 13 out of a possible 16 games for the Lions. In his first career professional game against the Phoenix Cardinals on September 10, Sanders ran for 71 yards on nine attempts and scored a rushing touchdown. Against the Chicago Bears, Sanders compiled 126 yards on 18 attempts and a touchdown but became injured with bruised ribs and a hip pointer that plagued him through the rest of the season. On October 1, Sanders only had one yard on five attempts against the Pittsburgh Steelers. Against the Minnesota Vikings, Sanders had 23 attempts for 99 yards. After the game, Vikings head coach Jerry Burns asked game officials to check if Sanders had applied silicone to himself, due to how difficult it was for players to tackle him: they found no illegal substance. On December 24, the final game of the season, he had 158 yards on 20 attempts to go along with three touchdowns against the Atlanta Falcons. During the game, the Lions installed a special phone line in one of the press boxes to monitor Christian Okoye who, at the time, was tied with Sanders for the league rushing title. When Okoye's game ended, Sanders trailed Okoye by only ten yards. Fontes offered Sanders the chance to return to the Lions' game to gain enough yards to pass Okoye, after Sanders was pulled from the game when the score was in the Lions' favor. Yet Sanders declined to return to the game, letting Okoye keep the rushing title. Sanders finished the season totaling 1,470 rushing yards off of 280 attempts and 14 touchdowns. His rushing total was both a rookie franchise record, and a franchise record for any running back in Lions history (both records held previously by Billy Sims). Sanders was awarded the NFL Offensive Rookie of the Year Award, and named to the PFWA All-Rookie Team. He was also selected to the Pro Bowl and was named a first-team All-Pro by the Associated Press (AP). The Lions struggled that season, posting a record and failing to make the postseason, despite winning five straight games to end the year.


title: Barry Sanders

text: On September 9, 1990, against the Tampa Bay Buccaneers, Sanders had 79 yards from 14 rushing attempts and a goal-line touchdown. Against the Green Bay Packers on September 30, Sanders had 20 attempts for 94 yards. Sanders had 16 attempts for 90 yards and a touchdown, coupled with five receptions for 135 yards receiving and a 47-yard receiving touchdown against the Kansas City Chiefs. On December 10 against the Los Angeles Raiders, Sanders was credited with a season-high 176 yards from 25 attempts and two touchdowns. On December 22 against the Packers, Sanders had 19 attempts for 133 yards and a touchdown in the 24–17 victory. Sanders had a productive year, finishing the year first in the NFL in rushing yards, with 1,304, becoming the first Lions running back to lead the league in rushing yards since Byron White in 1940. He ranked third in rushing touchdowns (13), and sixth in both attempts (255), and yards per attempt (5.1). As a result, Sanders was selected to his second Pro Bowl and was again named an AP first-team All-Pro. The Lions finished the year with a record and missed the postseason for the seventh consecutive season.


title: Barry Sanders

text: On September 1, 1991, Sanders was inactive for the Lions' 45–0 shutout loss against the Washington Redskins, due to having sore ribs before the opening kickoff. The loss was the franchise's worst in over 20 years. On November 24, 1991, against the Minnesota Vikings, Sanders dominated, with 220 rushing yards on 23 attempts and four touchdowns, a game the Lions won 34–14. Sanders dedicated the win to teammate Mike Utley, who suffered a career-ending spinal cord injury the previous game"." In the final game of the regular season against the Buffalo Bills, Sanders had 26 attempts for 108 yards and a touchdown, but fumbled in Lions territory, allowing the Bills to tie the game; the Lions would still be victorious, ending 17–14 in overtime. Sanders finished the regular season with 1,548 rushing yards from a workload of 342 attempts. He led the league in rushing touchdowns, with a career-high 16. Subsequently, he was selected to the Pro Bowl and AP first-team All-Pro team and awarded the Bert Bell Award. The 1992 season was the most successful season record-wise with Sanders starting at running back. With a record, the Lions clinched the NFC Central and made the postseason for the first time since 1983, with Fontes being awarded that year's National Football League Coach of the Year Award. Those 12 wins are the most in a season by the Lions franchise in its history. Having the seed in the NFC, the Lions skipped the Wild Card Round and advanced to the Divisional Round, where they faced the Dallas Cowboys. Sanders helped lead the Lions to their first postseason victory since the team won the 1957 NFL Championship Game. In the game, Sanders was held to only 22 yards rushing before he broke away for a 47-yard touchdown run, in which he broke several tackles to close out the 38–6 victory. In the NFC Championship Game, Sanders was held to eleven attempts for 44 yards in the Lions' blowout 10–41 loss to the eventual Super Bowl-winning Redskins. Sanders finished the postseason with 23 attempts for 113 yards and a touchdown. He would never win another playoff game in his career after that season.


title: Barry Sanders

text: On September 13, 1992, Sanders had 26 attempts for 66 yards against the Minnesota Vikings. Against the Washington Redskins the following week, Sanders recorded 14 attempts for only 34 yards. On November 22, Sanders compiled 29 attempts for 151 yards and a touchdown against the Cincinnati Bengals. His rushing total against the Bengals brought his career total to 5,202 rushing yards, passing Sims for a new franchise record. Sanders finished his final regular season game with 19 attempts for 104 yards against the San Francisco 49ers. Overall, Sanders was credited with 1,352 rushing yards from a workload of 312 attempts and nine touchdowns; his rushing yards total ranked fourth in the league, and his attempts ranked third. He was selected to the Pro Bowl and named an AP second-team All-Pro for the first time. The Lions regressed from their previous season, posting a record for the year, and missed the playoffs after making the conference championship the prior year.


title: Barry Sanders

text: On November 25, 1993, against the Chicago Bears, Sanders was credited with 16 attempts for 63 yards before leaving the game with an injury. It was revealed after the game that Sanders had suffered a torn MCL, and would miss three to five weeks. As a result, Sanders was inactive for the last five games of the regular season. In his final contract year, Sanders and the Lions agreed to a four-year, $17.2-million contract, making him the highest-paid running back in the NFL, and the third-highest-paid player overall, behind John Elway and Steve Young. Starting in only 11 games due to the injury, he finished in the top ten in multiple rushing categories. Sanders was fifth in the league in rushing yards (1,115 rushing yards), ninth in attempts (243), and second in rushing yards per game (101.4 rushing yards per game); with a career-low three rushing touchdowns. He was named to the Pro Bowl and an AP second-team All-Pro. The Lions finished the regular season with a record, clinching the NFC Central and a postseason berth. The Lions faced their division rival Green Bay Packers in the Wild Card Round. Sanders, after being cleared for the game, recorded 27 attempts for 169 yards, the best statistical postseason game of his career; but the Lions lost 24–28.


title: Barry Sanders

text: On September 11, 1994, Sanders struggled, as he had 12 attempts for only 16 yards in a 3–10 loss against the Minnesota Vikings. Against the Dallas Cowboys the following week, Sanders improved with a career-high 40 attempts for 194 yards. For his performance, he was named the NFC Offensive Player of The Week. On September 25, 1994, against the New England Patriots, Sanders recorded 18 attempts for 131 yards and two touchdowns. During the game, Sanders had one of the most memorable runs of his career. While rushing 39-yards for a touchdown, Sanders juked and spun his way to the end zone, causing Patriots safety Harlon Barnett to spin around trying to tackle Sanders. Barnett later spoke of the moment: "I'm not embarrassed about what happened. I thought I did pretty good. I got in front of him twice", Barnett then added, "I just didn't stay there." Against the Tampa Bay Buccaneers, Sanders had arguably the best statistical game of his career, compiling a career-high 237 rushing yards (franchise record), off of 26 attempts; setting the record for most rushing yards in a single game without scoring a touchdown. Sanders finished first in the league in rushing yards, recording 331 attempts for 1,883 rushing yards and scoring seven touchdowns. His single-season rushing total was fourth in NFL history up to that point. He totaled 2,166 yards from scrimmage, which, at the time, was the seventh-most ever in a season. As a result of his season, he was selected to the Pro Bowl and named an AP first-team All-Pro after the regular season. Sanders was named the NFL Offensive Player of the Year for the 1994 season and finished second in NFL Most Valuable Player voting behind Steve Young. The Lions finished the year with a record and made the postseason with a wild card spot. The Lions faced the Green Bay Packers again in the Wild Card Round, after being defeated by them the previous season. On December 31, Sanders struggled against the Packers and recorded what is viewed as the worst game of his career, having 13 attempts for -1 rushing yards. Six of his 13 attempts went for negative yardage, and the Lions as a team were held to only -4 rushing yards in the game, losing 12–16.


title: Barry Sanders

text: The 1995 season began against the Pittsburgh Steelers, Sanders recorded 21 rushing attempts for 108 yards. While the match was going on, Steelers cornerback Rod Woodson tore his ACL when he attempted to tackle Sanders. On September 25 against the San Francisco 49ers, Sanders had a down game, recording 17 attempts for only 24 yards. Against the Cleveland Browns, Sanders improved with 157 yards from 18 attempts and three touchdowns, including a 75-yard touchdown run, in a 38–20 victory. Sanders finished with 314 attempts for 1,500 yards and 11 touchdowns. For his season, Sanders was selected to the Pro Bowl and named an AP first-team All-Pro. The Lions posted a record and made the postseason with a wild card spot, where the Lions faced the Philadelphia Eagles in the Wild Card Round. Sanders had ten attempts for 40 yards as the Lions' rushing game was stuffed by the Eagles' defense. The Lions were likewise overwhelmed by the Eagles' offense and faced a 44-point deficit in the third quarter 7–51, eventually losing the game 37–58; despite the victory being guaranteed by teammate Lomas Brown. At the time, this was the highest-scoring postseason game in NFL history, with 95 points scored. This record was bested by one point in a 51–45 victory by the Arizona Cardinals over the Green Bay Packers in 2009.


title: Barry Sanders

text: In the first game of the season against the Minnesota Vikings, Sanders recorded 24 rushing attempts for 163 rushing yards. Against the Oakland Raiders, Sanders had nine attempts for only 36 yards. On November 3 against the Green Bay Packers, Sanders had 20 attempts for 152 yards and a touchdown. Against the Seattle Seahawks on November 17, Sanders had 16 attempts for 134 yards and a touchdown. Against the Chicago Bears the following week, Sanders had 21 attempts for 107 yards and a touchdown. Sanders had 20 attempts for 134 yards and a touchdown against the Vikings, but a missed two-point conversion attempt after his touchdown resulted in the Lions losing 22–24. In the final game of the season, he recorded 28 attempts for 175 yards against the San Francisco 49ers. Overall, Sanders finished the regular season first in the league in rushing yards with 1,553 rushing yards from 307 attempts. He scored 11 rushing touchdowns, and had 97.1 rushing yards per game, which was first in the league. At this point in his career, Sanders had 11,725 career rushing yards, seventh all-time, and ranked eighth all-time in career rushing touchdowns, with 84. The Lions regressed, posting a record, and failed to make the postseason after three straight playoff seasons from 1993 to 1995; though Sanders still made the Pro Bowl and was named an AP second-team All-Pro.Before the start of the 1997 season, Fontes was fired after nine seasons coaching the Lions, and replaced by Bobby Ross; Sanders was saddened by Fontes' firing, believing he deserved another chance at coaching the team. On September 7 against the Tampa Bay Buccaneers, Sanders struggled on the ground, having 10 attempts for only 20 yards, but recorded 102 receiving yards and a touchdown. On October 12, Sanders dominated with 215 yards from 24 attempts and two touchdowns against the Buccaneers, passing Jim Brown to be the fourth-ranked career rushing leader in NFL history, with 12,513 career rushing yards; he also caught a seven-yard touchdown pass. Against the Indianapolis Colts, Sanders had another stellar performance, compiling 24 attempts for 216 yards and two touchdowns (including one of 80 yards). With the win, Sanders became the first running back with ten consecutive games with 100 yards rushing in a season, and became the first running back to have three touchdowns of 80+ yards in a season. Against the Chicago Bears, Sanders had 19 attempts for 167 yards and three touchdowns, passing Eric Dickerson to become the second-ranked rusher for career yards behind Walter Payton On December 21, 1997, Sanders entered the season finale against the New York Jets needing at least 131 rushing yards to reach 2,000 for the season; both teams needed a win to clinch a playoff birth. Sanders reached the 2,000 mark on a two-yard run; finishing the game with 23 attempts for 184 yards and a touchdown; helping the Lions edge the Jets 13–10. Sanders had a season that's considered among the greatest ever by a running back. He recorded 2,053 rushing yards, which was first in the league that season, from 335 attempts, and 11 touchdowns, becoming just the third running back in history to reach 2,000 rushing yards in a season. For his accomplishments, he credited his offensive linemen, stating: "Without them, I wouldn't have run far at all." Sanders rushed for 100+ yards in the season's final 14 games, an NFL record. With 2,358 total scrimmage yards, he broke the single-season record for scrimmage yards that was held by Marcus Allen; the record was broken two seasons later by Marshall Faulk, and again by Chris Johnson in 2009. Sanders was named to the Pro Bowl and AP first-team All-Pro, and awarded the Bert Bell Award. Sanders was also awarded his second NFL Offensive Player of the Year Award, and the NFL Most Valuable Player (co-won with Brett Favre). The Lions posted a record and clinched a wild card spot as the No. 5 seed in the NFC. Sanders and the Lions faced the Buccaneers, whom were playing their first home postseason game in 18 years. Sanders had 18 attempts for 65 yards as the Lions lost 10–20, after quarterback Scott Mitchell left the game with an injury in the third quarter.


title: Barry Sanders

text: On September 13, 1998, against the Cincinnati Bengals, Sanders recorded 185 rushing yards from 26 rushing attempts with three touchdowns. Sanders had 22 attempts for 69 yards in a 6–29 loss against the Minnesota Vikings. On November 26, 1998, against the Pittsburgh Steelers, Sanders had a down game, with 20 attempts for only 33 rushing yards; the Lions were still victorious 19–16 in overtime. Against the Jacksonville Jaguars, Sanders had 18 attempts for 102 yards. In Sanders' final game of his career, on December 27, 1998, he had 19 attempts for 41 yards in a 10–19 loss against the Baltimore Ravens. Sanders capped off his final season with 1,491 rushing yards (fourth in the league), from a career-high 343 attempts (fifth in the league), and four touchdowns. He was nine yards short of completing five straight seasons with at least 1,500 rushing yards. He was selected to his tenth Pro Bowl, and named an AP second-team All-Pro. The Lions struggled despite Sanders' performances, going , and failing to make the postseason.


title: Barry Sanders

text: On July 27, 1999, Sanders announced his retirement from pro football, on the day before Lions training camp was set to start. His retirement was made public by faxing a letter to "The Wichita Eagle," his hometown newspaper. In the letter, Sanders wrote: "Shortly after the end of last season, I felt that I probably would not return for the 1999–2000 season. I also felt that I should take as much time as possible to sort through my feelings and make sure that my feelings were back with conviction. Today, I officially declare my departure from the NFL."He left football healthy, having gained 15,269 rushing yards (the most ever by any NFL player in a 10-year span). He retired within 1,457 rushing yards of Walter Payton's career rushing mark of 16,726 yards. It has been speculated that Sanders would have surpassed the record if he hadn't retired early, a view held by Emmitt Smith, the eventual holder of the record. His father praised him for his decision, saying that it "took guts." Sanders took time in his decision, waiting "till the last minute." His retirement voided $20.9 million in collective salary and bonuses, along with millions of dollars in endorsements.


title: Barry Sanders

text: Sanders' retirement came somewhat unexpectedly and was a matter of controversy. Two years earlier, Sanders had renewed his contract with the Lions for $34.56 million over six years with an $11 million signing bonus. The Lions demanded that he return $7.37 million of the bonus. Sanders' agents refused, and the Lions filed a grievance with the NFL. On February 15, 2000, an arbitrator ruled that Sanders had to immediately repay $1,833,000 (a sixth of the bonus), with the remaining bonus to be repaid over each of the three years Sanders had left on the contract provided he stayed retired. Before the ruling, Sanders offered to pay back the entire bonus in return for him being traded to another team or his release.


title: Barry Sanders

text: It was thought by some that Lions head coach Bobby Ross himself may have actually been the reason for Sanders' early retirement, but in his autobiography "Barry Sanders: Now You See Him", Sanders praised Ross as a head coach who had nothing directly to do with his retirement. It was more his frustration with the management and direction of the Lions and the resulting lack of success that contributed to his retirement, as Sanders revealed in his autobiography: "My retirement letter didn't even hint at my frustration, because I didn't want to take shots at people as I left ... Management had let quality players slip away. We'd been losing for years. Now we were right back where we were when I arrived." He wrote: "A goal that I still hadn't realized was playing in the Super Bowl, and all of the statistical achievements didn't put the team any closer to playing in the big game." Sanders has since patched things up with the Lions, rejoining the organization in a paid role as a team ambassador in 2017.


title: Barry Sanders

text: Sanders is widely regarded as one of the greatest running backs in the history of the NFL, being ranked No. 1 by Bleacher Report and in the top ten by other media outlets. When he retired, Sanders was ranked second all-time in career rushing yards with 15,269 rushing yards, sixth all-time in career rushing touchdowns with 99 rushing touchdowns, and second all-time in career rushing attempts with 3,062 attempts. As of 2022, Sanders is still ranked in the top ten in all three statistics. Over his entire career, Sanders averaged 1,527 rushing yards per season, and 99.8 rushing yards per game, the latter stat second to Jim Brown. He never went below 1,000 yards in any of his ten seasons and has the second-most career 1,000-yard rushing seasons, with ten. Sanders was a notable bright spot on a Lions franchise that had endured years of unsuccessful play, helping to lead the team to their first playoff victory in decades. At the same time, Sanders only won one playoff game throughout his ten-year career, with NFL Network's Derrin Horton stating: "Not even Barry Sanders... could pull Detroit out of the playoff snakebit," in reference to the team's postseason failures. The Lions' overall unsuccessful play was noted for possibly being a reason for Sanders' early retirement. His number, No. 20, was retired by the Lions on November 25, 2004, along with Sims and Lem Barney (who wore the same number). Sanders was also honored by the Lions when they inducted him into the Pride of the Lions, the franchise's ring of honor. Throughout his career, he achieved Pro Bowl and All-Pro status in all ten of his NFL seasons. Sanders was named first-team All-Pro six times; and named second-team All-Pro four times. Sanders was named NFL Offensive Player of the Year in 1994 and 1997, awarded two Bert Bell Awards, and was named to the 1990s NFL All-Decade team. Both the Pro Football Hall of Fame and Oklahoma Sports Hall of Fame enshrined him on August 8, 2004 and August 21, 2005, respectively. At the age of 36, Sanders became the second-youngest player to be inducted into the Pro Football Hall of Fame. In 2019, Sanders was named to the NFL 100th Anniversary All-Time Team. In 2007, he was ranked by NFL Network's "NFL Top 10" series as the most elusive runner in NFL history, and in 2012 was placed No. 1 on their list of the greatest players never to play in a Super Bowl.


title: Barry Sanders

text: Sanders led the NFL in rushing yards four times (second to Brown), and in rushing touchdowns once in 1994. He co-won the NFL Most Valuable Player Award in 1997 (with Brett Favre) after rushing for 2,053 yards in 16 games, becoming the third running back to surpass 2,000 yards. In the same season, Sanders totaled a record 2,358 yards from scrimmage, later surpassed by both Marshall Faulk and Chris Johnson. By the end of his career, Sanders was known as "one of the game's most electrifying runners", as described by the Pro Football Hall of Fame; this was a view shared by "Sports Illustrated," who described him as "running circles around NFL defenses with an electrifying style unlike anything the league has seen." His 1989 season is regarded as one of the best all-time by a rookie running back, ranked No. 3 by NFL analyst Elliot Harrison, and No 4. by ESPN analyst Jeff Merron. In 1999, an ESPN survey of journalists, athletes, and other sports figures ranked Sanders as the 76th greatest North American athlete of the 20th-century.


title: Barry Sanders

text: Although he sat behind fellow Pro Football Hall of Fame running back Thurman Thomas on the depth chart for his first two collegiate seasons, Sanders is considered one of the greatest college football players of all time. His Heisman trophy-winning season in 1988, in which he set single-season college football records for most rushing yards gained, touchdowns scored, and total scrimmage yards (among other records), is often considered the greatest individual college football season ever, ranked No. 1 by ESPN and Sporting News. In commemoration of the 150th-year of college football, Sanders was honored during halftime at the CFP National Championship game on January 13, 2020, as the No. 9 player of all time.


title: Barry Sanders

text: In contrast to many of the star players of his era, Sanders was noted for his on-field humility. Despite his flashy playing style, Sanders was rarely seen celebrating after the whistle was blown; instead, he handed the ball to a referee, and was never tempted into celebrating any further. He was recognized for putting his team's success over his stats, as shown when he denied a request from head coach Wayne Fontes to return to play in a game so that he could gain enough rushing yards to become the rushing leader for that season. He disliked speaking to the press, and rarely spoke about his accomplishments publicly. When reflecting on his career, ESPN described Sanders as a "humble superstar."


title: Barry Sanders

text: Sanders is a devout Christian. He and his former wife Lauren Campbell Sanders, a former news anchor for WDIV in Detroit, filed for divorce in February 2012 after 12 years of marriage. Sanders' brother, Byron, was the starting running back at Northwestern University and was drafted by the Chicago Bears. Byron was cut by the Bears two months after joining the team.


title: Barry Sanders

text: Sanders has four sons; the youngest three are from his marriage to Campbell. Sanders' oldest son, Barry J. Sanders, played running back for Stanford University from 2012 to 2015, and at Oklahoma State University in 2016, after a highly successful high school career. In 2003, Sanders co-wrote his autobiography, "Barry Sanders: Now You See Him: His Story In His Own Words," with Mark McCormick. He has reportedly donated to several charities, under the condition that they do not disclose his participation in any of them.


title: Barry Sanders

text: Sanders introduced ESPN's "Monday Night Football" game between the Chicago Bears and Detroit Lions on October 10, 2011. In April 2013, Sanders made it to the finals in the EA Sports "Madden NFL 25" cover vote by beating Ron Rivera in Round One, Marcus Allen in Round Two, Ray Lewis in Round Three, Joe Montana in the quarter-finals, and Jerry Rice in the semi-finals. He beat Adrian Peterson to become the next cover athlete, the 1st player to appear on the cover of "Madden NFL Football" more than once (he appeared in the background of the "Madden NFL 2000" cover).


title: Jonita Gandhi

text: Jonita Gandhi is a Canadian playback singer of Indian descent. She has recorded songs predominantly in Hindi and Tamil languages with few in Punjabi, Telugu, Marathi, Gujarati, Bengali, Kannada and Malayalam languages. Some of her most acclaimed songs include "The Breakup Song", "Mental Manadhil", "Chellama and" "Arabic Kuthu". She is also well known for her YouTube presence. Her singing debut started through "Chennai Express" title track (in 2013).


title: Jonita Gandhi

text: Gandhi was born in a Punjabi family from Delhi. Her family emigrated to Brampton, Canada when she was nine months old, where she was raised. Her family later settled in Mississauga.


title: Jonita Gandhi

text: Gandhi studied in Turner Fenton Secondary School and attended the Ivey Business School of the University of Western Ontario where she completed her degrees in health science and business in 2012. She has had formal training in Western and Hindustani classical singing.


title: Jonita Gandhi

text: Gandhi grew up around music as both her father and brother were part time musicians. They would often perform cover songs together at live community events. At age 16, she auditioned for Canadian Idol but didn't get past the audition rounds. She began making YouTube covers from her bedroom, sometimes featuring other local musicians including Akash Gandhi. The videos quickly went viral and led to a myriad of opportunities to perform. Her hits on YouTube began with covers of well-known Hindi-film songs, such as, "Pani Da Rang", "Tujhko Jo Paaya", "Tum Hi Ho", "Suhaani Raat", "Yeh Honsla" and many others. Her beginning concerts typically consisted of these covers.


title: Jonita Gandhi

text: Her jump to playback singing began with an opportunity to perform alongside Sonu Nigam. This tour crossed various countries including Russia, UK, US and the Caribbean. Afterwards, her sights were set on starting a career in the Bollywood music industry. Gandhi started playback singing with Chennai Express. The music for this film was composed by Vishal–Shekhar. She further worked in other Bollywood movies like Highway, singing both "Kahaan Hoon Main" and "Implosive Silence".


title: Jonita Gandhi

text: Gandhi worked as a playback singer with music directors including A. R. Rahman and Pritam. Rahman featured Gandhi in the concert film One Heart (film). Gandhi performed at the 2016 Jubilee Games in Dubai with Salim–Sulaiman and with Amit Trivedi on MTV Unplugged.


title: Jonita Gandhi

text: In 2020, Jonita Gandhi was involved in mentoring and judging the Indian kids singing reality show Taare Zameen Par on StarPlus


title: Jonita Gandhi

text: As of 2021, Gandhi is set to make her film debut with director Vignesh Shivan's Tamil film "Walking/Talking Strawberry Icecream", starring Krishnakumar Balasubramanian.


title: Kazakhs

text: The Kazakhs (also spelled Qazaqs; Kazakh: , , , , , ; the English name is transliterated from Russian; ) are a Turkic ethnic group native to northern parts of Central Asia, chiefly Kazakhstan, but also parts of Uzbekistan and Russia, as well as China (Northern Xinjiang) and Mongolia (Bayan-Ölgii Province). The Kazakhs are descendants of the ancient Turkic tribes and the medieval Mongolic or Turco-Mongol tribes.


title: Kazakhs

text: Kazakh identity is of medieval origin and was strongly shaped by the foundation of the Kazakh Khanate between 1456 and 1465, when following disintegration of the Golden Horde, several tribes under the rule of the sultans Janibek and Kerei departed from the Khanate of Abu'l-Khayr Khan in hopes of forming a powerful khanate of their own.


title: Kazakhs

text: "Kazakh" is used to refer to ethnic Kazakhs, while the term "Kazakhstani" usually refers to all inhabitants or citizens of Kazakhstan, regardless of ethnicity.


title: Kazakhs

text: The Kazakhs likely began using that name during the 15th century. There are many theories on the origin of the word Kazakh or Qazaq. Some speculate that it comes from the Turkic verb ("wanderer, vagabond, warrior, free, independent") or that it derives from the Proto-Turkic word (a wheeled cart used by the Kazakhs to transport their yurts and belongings).


title: Kazakhs

text: Another theory on the origin of the word Kazakh (originally ) is that it comes from the ancient Turkic word , first mentioned on the 8th century Turkic monument of Uyuk-Turan. According to Turkic linguist Vasily Radlov and Orientalist Veniamin Yudin, the noun ' derives from the same root as the verb ' ("to obtain", "to gain"). Therefore, "" defines a type of person who wanders and seeks gain.


title: Kazakhs

text: Kazakhs's history is full of nomadic civilisations of the Great Steppe, represented by numerous nomadic state entities, including the Sakas (Asian Scythians), the Huns, the Turkic Khaganate, the Western Turkic Khaganate, the Mongol Empire, the Golden Horde and the Kazakh Khanate, which was established in 1465.


title: Kazakhs

text: Kazakh was a common term throughout medieval Central Asia, generally with regard to individuals or groups who had taken or achieved independence from a figure of authority. Timur described his own youth without direct authority as his ("freedom", "Qazaq-ness").


title: Kazakhs

text: In Turko-Persian sources, the term "Özbek-Qazaq" first appeared during the middle of the 16th century, in the "Tarikh-i-Rashidi" by Mirza Muhammad Haidar Dughlat, a Chagatayid prince of Kashmir. In this manuscript, the author locates Kazakh in the eastern part of "Desht-i Qipchaq". According to Tarikh-i-Rashidi, the first Kazakh union was created 1465/1466 AD. The state was formed by nomads who settled along the border of Moghulistan, and was called "Uzbeg-Kazák".


title: Kazakhs

text: At the time of the Uzbek conquest of Central Asia, Abu'l-Khayr Khan, a descendant of Shiban, had disagreements with the Kazakh sultans Kerei and Janibek, descendants of Urus Khan. These disagreements probably resulted from the crushing defeat of Abu'l-Khayr Khan at the hands of the Kalmyks. Kerei and Janibek moved with a large following of nomads to the region of Zhetysu on the border of Moghulistan and set up new pastures there with the blessing of the Chagatayid khan of Moghulistan, Esen Buqa II, who hoped for a buffer zone of protection against the expansion of the Oirats.


title: Kazakhs

text: In the 17th century, Russian convention seeking to distinguish the Qazaqs of the steppes from the Cossacks of the Imperial Russian Army suggested spelling the final consonant with "kh" instead of "q" or "k", which was officially adopted by the USSR in 1936.


title: Kazakhs

text: The Ukrainian term Cossack probably comes from the same Kipchak etymological root, meaning wanderer, brigand, or independent free-booter.


title: Kazakhs

text: Their nomadic pastoral lifestyle made Kazakhs keep an epic tradition of oral history. The nation, which amalgamated nomadic tribes of various Kazakh origins, managed to preserve the distant memory of the original founding clans. It was important for Kazakhs to know their genealogical tree for no less than seven generations back (known as ', from the Arabic word ' – "tree").


title: Kazakhs

text: In modern Kazakhstan, tribalism is fading away in business and government life. Still it is common for Kazakhs to ask each other the tribe they belong to when they become acquainted with one another. Now, it is more of a tradition than necessity, and there is no hostility between tribes. Kazakhs, regardless of their tribal origin, consider themselves one nation.


title: Kazakhs

text: Those modern-day Kazakhs who yet remember their tribes know that their tribes belong to one of the three Zhuz (juz, roughly translatable as "horde" or "hundred"):


title: Kazakhs

text: There is much debate surrounding the origins of the Hordes. Their age is unknown so far in extant historical texts, with the earliest mentions in the 17th century. The Turkologist Velyaminov-Zernov believed that it was the capture of the important cities of Tashkent, Yasi, and Sayram in 1598 by Tevvekel (Tauekel/Tavakkul) Khan that separated the Qazaqs, as they possessed the cities for only part of the 17th century. The theory suggests that the Qazaqs then divided among a wider territory after expanding from Zhetysu into most of the Dasht-i Qipchaq, with a focus on the trade available through the cities of the middle Syr Darya, to which Sayram and Yasi belonged. The Junior juz originated from the Nogais of the Nogai Horde.


title: Kazakhs

text: The Kazakh language is a member of the Turkic language family, as are Uzbek, Kyrgyz, Tatar, Uyghur, Turkmen, modern Turkish, Azeri and many other living and historical languages spoken in Eastern Europe, Central Asia, Xinjiang, and Siberia.


title: Kazakhs

text: Kazakh belongs to the Kipchak (Northwestern) group of the Turkic language family. Kazakh is characterized, in distinction to other Turkic languages, by the presence of in place of reconstructed proto-Turkic and in place of ; furthermore, Kazakh has where other Turkic languages have .


title: Kazakhs

text: Kazakh, like most of the Turkic language family lacks phonemic vowel length, and as such there is no distinction between long and short vowels.


title: Kazakhs

text: Kazakh was written with the Arabic script until the mid-19th century, when a number of educated Kazakh poets from Muslim madrasahs incited a revolt against Russia. Russia's response was to set up secular schools and devise a way of writing Kazakh with the Cyrillic alphabet, which was not widely accepted. By 1917, the Arabic script for Kazakh was reintroduced, even in schools and local government.


title: Kazakhs

text: In 1927, a Kazakh nationalist movement sprang up against the Soviet Union but was soon suppressed. As a result, the Arabic script for writing Kazakh was banned and the Latin alphabet was imposed as a new writing system. In an effort to Russianize the Kazakhs, the Latin alphabet was in turn replaced by the Cyrillic alphabet in 1940 by Soviet interventionists. Today, there are efforts to return to the Latin script.


title: Kazakhs

text: Kazakh is a state (official) language in Kazakhstan. It is also spoken in the Ili region of the Xinjiang Uyghur Autonomous Region in the People's Republic of China, where the Arabic script is used, and in western parts of Mongolia (Bayan-Ölgii and Khovd province), where Cyrillic script is in use. European Kazakhs use the Latin alphabet.


title: Kazakhs

text: In the late 14th century, the Golden Horde propagated Islam in its state. Islam in Kazakhstan peaked during the era of the Kazakh Khanate, especially under rulers such as Ablai Khan and Kasym Khan. Another wave of conversions among the Kazakhs occurred during the 15th and 16th centuries via the efforts of Sufi orders. During the 18th century, Russian influence toward the region rapidly increased throughout Central Asia. Led by Catherine, the Russians initially demonstrated a willingness in allowing Islam to flourish as Muslim clerics were invited into the region to preach to the Kazakhs, whom the Russians viewed as "savages" and "ignorant" of morals and ethics. However, Russian policy gradually changed toward weakening Islam by introducing pre-Islamic elements of collective consciousness. Such attempts included methods of eulogizing pre-Islamic historical figures and imposing a sense of inferiority by sending Kazakhs to highly elite Russian military institutions. In response, Kazakh religious leaders attempted to bring in pan-Turkism, though many were persecuted as a result. During the Soviet era, Muslim institutions survived only in areas that Kazakhs significantly outnumbered non-Muslims, such as non-indigenous Russians, by everyday Muslim practices. In an attempt to conform Kazakhs into Communist ideologies, gender relations and other aspects of Kazakh culture were key targets of social change.


title: Kazakhs

text: In more recent times, however, Kazakhs have gradually employed a determined effort in revitalizing Islamic religious institutions after the fall of the Soviet Union. Most Kazakhs continue to identify with their Islamic faith, and even more devotedly in the countryside. Those who claim descent from the original Muslim soldiers and missionaries of the 8th-century command substantial respect in their communities. Kazakh political figures have also stressed the need to sponsor Islamic awareness. For example, the Kazakh Foreign Affairs Minister, Marat Tazhin, recently emphasized that Kazakhstan attaches importance to the use of "positive potential Islam, learning of its history, culture and heritage."


title: Kazakhs

text: Pre-Islamic beliefs, such as worship of the sky, the ancestors, and fire, continued to a great extent to be preserved among the common people, however. Kazakhs believed in the supernatural forces of good and evil spirits, of wood goblins and giants. To protect themselves from them and from the evil eye, Kazakhs wore protection beads and talismans. Shamanic beliefs are still widely preserved among Kazakhs, as well as the belief in the strength of the bearers of that worship, the shamans, which Kazakhs call "bakhsy". Unlike the Siberian shamans, who used drums during their rituals, Kazakh shamans, who could also be men or women, played (with a bow) on a stringed instrument similar to a large violin. At present both Islamic and pre-Islamic beliefs continue to be found among Kazakhs, especially among the elderly. According to 2009 national census 39,172 ethnic Kazakhs are Christians (0.0038% of all Kazakhstani Kazakhs).


title: Kazakhs

text: Kazakhs are a Turkic-speaking ethnic group, who formed from various nomadic tribes and clans, sharing a common lifestyle.


title: Kazakhs

text: Recent linguistic, genetic and archaeological evidence suggests that the earliest Turkic peoples descended from agricultural communities in Northeast Asia and Northeast China who moved westwards into Mongolia in the late 3rd millennium BC, where they adopted a pastoral lifestyle. By the early 1st millennium BC, these peoples had become equestrian nomads. In subsequent centuries, the steppe populations of Central Asia appear to have been progressively replaced and Turkified by East Asian nomadic Turks, moving out of Mongolia.


title: Kazakhs

text: The Kazakhs emerged in the 15th century from an amalgam of Turkic tribes and of Turkified Mongol tribes. Kazakhs formed as an ethno-linguistic group during the early 15th century from a confederation of several pastoral nomadic groups of Northern Central Asia. The Kazakhs are the most northerly of the Central Asian peoples, inhabiting a large expanse of territory in northern Central Asia and southern Siberia known as the Kazakh Steppe. The tribal groups formed a powerful confederation that grew wealthy on the trade passing through the steppe lands along the fabled Silk Road.


title: Kazakhs

text: Genomic research found that Kazakhs are of primarily East Asian origin, and harbor two East Asian-related components, one dominant component, commonly found among Northern Asian populations (associated with the Northeast Asian "Devil’s Gate_N" sample from the Amur region) and another minor component associated with historical Yellow River farmers. According to one study, West-Eurasian related admixture among Kazakhs is estimated at a mean average of about 35% to 37.5%, and is suggested to have been derived from assimilated Bronze Age Steppe pastoralists. Another study estimated a lower average Western admixture of slightly less than 30%. These results are inline with the historical expansion of Turkic peoples westwards, and replacement and assimilation of previous groups. Neighboring Uzbeks, Kyrgyz, Tubalar, and the Xinjiang Ölöd tribe, have the strongest resemblance to the Kazakh genome.


title: Kazakhs

text: A study on allele frequency and genetic polymorphism by Katsuyama et al., found that Kazakhs cluster together with Japanese people, Hui people, Han Chinese, and Uyghurs.


title: Kazakhs

text: A 2020 genetic study on the Kazakh genome, by Seidualy et al., found that the Kazakh people formed from highly mixed historical Central Asian populations. Ethnic Kazakhs were modeled to derive about ~63.2% ancestry from an East Asian-related population, specifically from a Northeast Asian source sample (Devil’s Gate 1), ~30.8% ancestry from West-Eurasian (European-related) populations (presumably from Bronze Age Steppe pastoralists), and ~6% ancestry from a broadly South Asian population. Overall, Kazakhs show their closest genetic affinity with other Central Asian populations, namely, Kalmyk, Uzbek and Kyrgyz people, but also Mongolians. MSMC analyses suggest that the main ancestral lineage of Kazakhs split from Mongolians and other Northeast Asians about 7,000 years ago, while their divergence from Koryaks was estimated to be 10,000 years ago.


title: Kazakhs

text: According to mitochondrial DNA studies (where sample consisted of only 246 individuals), the main maternal lineages of Kazakhs are: D (17.9%), C (16%), G (16%), A (3.25%), F (2.44%) of East-Eurasian origin (55%), and haplogroups H (14.1), T (5.5), J (3.6%), K (2.6%), U5 (3%), and others (12.2%) of West-Eurasian origin (41%). An analysis of ancient Kazakhs found that East Asian haplogroups such as A and C did not begin to move into the Kazakh steppe region until around the time of the Xiongnu (1st millennia BCE), which is around the onset of the Sargat Culture as well .


title: Kazakhs

text: Gokcumen "et al." (2008) tested the mtDNA of a total of 237 Kazakhs from Altai Republic and found that they belonged to the following haplogroups: D(xD5) (15.6%), C (10.5%), F1 (6.8%), B4 (5.1%), G2a (4.6%), A (4.2%), B5 (4.2%), M(xC, Z, M8a, D, G, M7, M9a, M13) (3.0%), D5 (2.1%), G2(xG2a) (2.1%), G4 (1.7%), N9a (1.7%), G(xG2, G4) (0.8%), M7 (0.8%), M13 (0.8%), Y1 (0.8%), Z (0.4%), M8a (0.4%), M9a (0.4%), and F2 (0.4%) for a total of 66.7% mtDNA of Eastern Eurasian origin or affinity and H (10.5%), U(xU1, U3, U4, U5) (3.4%), J (3.0%), N1a (3.0%), R(xB4, B5, F1, F2, T, J, U, HV) (3.0%), I (2.1%), U5 (2.1%), T (1.7%), U4 (1.3%), U1 (0.8%), K (0.8%), N1b (0.4%), W (0.4%), U3 (0.4%), and HV (0.4%) for a total of 33.3% mtDNA of West-Eurasian origin or affinity. Comparing their samples of Kazakhs from Altai Republic with samples of Kazakhs from Kazakhstan and Kazakhs from Xinjiang, the authors have noted that "haplogroups A, B, C, D, F1, G2a, H, and M were present in all of them, suggesting that these lineages represent the common maternal gene pool from which these different Kazakh populations emerged."


title: Kazakhs

text: In every sample of Kazakhs, D (predominantly northern East Asian, such as Japanese, Okinawan, Korean, Manchu, Mongol, Han Chinese, Tibetan, "etc.", but also having several branches among indigenous peoples of the Americas) is the most frequently observed haplogroup (with nearly all of those Kazakhs belonging to the D4 subclade), and the second-most frequent haplogroup is either H (predominantly European) or C (predominantly indigenous Siberian, though some branches are present in the Americas, East Asia, and eastern and northern Europe).


title: Kazakhs

text: In a sample of 54 Kazakhs and 119 Altaian Kazakh, the main paternal lineages of Kazakhs are: C (66.7% and 59.5%), O (9% and 26%), N (2% and 0%), J (4% and 0%), R (9% and 1%) respectively.


title: Kazakhs

text: Huge drop in population of Ethnic Kazakhs between 1897 and 1959 years caused by colonial politics of Russian Empire, then genocide


title: Kazakhs

text: which occurred during Stalin Regime. Sarah Cameron (Associate Professor of University of Maryland) described this genocide on her book, "The Hungry Steppe: Famine, Violence, and the Making of Soviet Kazakhstan".


title: Kazakhs

text: In Russia, the Kazakh population lives primarily in the regions bordering Kazakhstan. According to latest census (2002) there are 654,000 Kazakhs in Russia, most of whom are in the Astrakhan, Volgograd, Saratov, Samara, Orenburg, Chelyabinsk, Kurgan, Tyumen, Omsk, Novosibirsk, Altai Krai and Altai Republic regions. Though ethnically Kazakh, after the dissolution of the Soviet Union in 1991, those people acquired Russian citizenship.


title: Kazakhs

text: Kazakhs migrated into Dzungaria in the 18th century after the Dzungar genocide resulted in the native Buddhist Dzungar Oirat population being massacred.


title: Kazakhs

text: Kazakhs, called "" in Chinese () are among 56 ethnic groups officially recognized by the People's Republic of China. According to the census data of 2010, Kazakhs had a population of 1.462 million, ranking 17th among all ethnic groups in China. Thousands of Kazakhs fled to China during the 1932–1933 famine in Kazakhstan.


title: Kazakhs

text: In 1936, after Sheng Shicai expelled 30,000 Kazakhs from Xinjiang to Qinghai, Hui led by General Ma Bufang massacred their fellow Muslim Kazakhs, until there were 135 of them left.


title: Kazakhs

text: From Northern Xinjiang over 7,000 Kazakhs fled to the Tibetan-Qinghai plateau region via Gansu and were wreaking massive havoc so Ma Bufang solved the problem by relegating Kazakhs to designated pastureland in Qinghai, but Hui, Tibetans, and Kazakhs in the region continued to clash against each other. Tibetans attacked and fought against the Kazakhs as they entered Tibet via Gansu and Qinghai. In northern Tibet, Kazakhs clashed with Tibetan soldiers, and the Kazakhs were sent to Ladakh. Tibetan troops robbed and killed Kazakhs east of Lhasa at Chamdo when the Kazakhs were entering Tibet.


title: Kazakhs

text: In 1934, 1935, and from 1936 to 1938 Qumil Elisqan led approximately 18,000 Kerey Kazakhs to migrate to Gansu, entering Gansu and Qinghai.


title: Kazakhs

text: In China there is one Kazakh autonomous prefecture, the Ili Kazakh Autonomous Prefecture in the Xinjiang Uyghur Autonomous Region and three Kazakh autonomous counties: Aksai Kazakh Autonomous County in Gansu, Barkol Kazakh Autonomous County and Mori Kazakh Autonomous County in the Xinjiang Uyghur Autonomous Region.


title: Kazakhs

text: At least one million Uyghurs, Kazakhs and other ethnic Muslims in Xinjiang have been detained in mass detention camps, termed "reeducation camps", aimed at changing the political thinking of detainees, their identities, and their religious beliefs.


title: Kazakhs

text: In the 19th century, the advance of the Russian Empire troops pushed Kazakhs to neighboring countries. In around 1860, part of the Middle Jüz Kazakhs came to Mongolia and were allowed to settle down in Bayan-Ölgii, Western Mongolia and for most of the 20th century they remained an isolated, tightly knit community.


title: Kazakhs

text: Ethnic Kazakhs (so-called Altaic Kazakhs or Altai-Kazakhs) live predominantly in Western Mongolia in Bayan-Ölgii Province (88.7% of the total population) and Khovd Province (11.5% of the total population, living primarily in Khovd city, Khovd sum and Buyant sum). In addition, a number of Kazakh communities can be found in various cities and towns spread throughout the country. Some of the major population centers with a significant Kazakh presence include Ulaanbaatar 90% in khoroo #4 of Nalaikh düüreg, Töv and Selenge provinces, Erdenet, Darkhan, Bulgan, Sharyngol (17.1% of population total) and Berkh cities.


title: Kazakhs

text: During the Qajar period, Iran bought Kazakh slaves who were falsely masqueraded as Kalmyks by slave dealers from the Khiva and Turkmens.


title: Kazakhs

text: Kazakhs of the Aday tribe inhabited the border regions of the Russian Empire with Iran since the 18th century. The Kazakhs made up 20% of the population of the Trans-Caspian region according to the 1897 census. As a result of the Kazakhs' rebellion against the Russian Empire in 1870, a significant number of Kazakhs became refugees in Iran.


title: Kazakhs

text: Iranian Kazakhs live mainly in Golestan Province in northern Iran. According to ethnologue.org, in 1982 there were 3000 Kazakhs living in the city of Gorgan. Since the fall of the Soviet Union, the number of Kazakhs in Iran decreased because of emigration to their historical motherland.


title: Kazakhs

text: Kazakhs fled to Afghanistan in the 1930s escaping Bolshevik persecution. Kazakh historian Gulnar Mendikulova cites that there were between 20,000 and 24,000 Kazakhs in Afghanistan as of 1978. Some assimilated locally and cannot speak the Kazakh language.


title: Kazakhs

text: As of 2021, there are about 200 Kazakhs remaining in Afghanistan according to Kazakhstan's foreign ministry. Locals claim that many live in Kunduz and others in Takhar Province, Baghlan Province, Mazar-i-Sharif and Kabul.


title: Kazakhs

text: Afghan Kypchaks are Aimak (Taymani) tribe of Kazakh origin that can be found in Obe District to the east of the western Afghan province of Herat, between the rivers Farāh Rud and Hari Rud. There are approximately 440,000 Afghan Kipchaks.


title: Kazakhs

text: Turkey received refugees from among the Pakistan-based Kazakhs, Turkmen, Kirghiz, and Uzbeks numbering 3,800 originally from Afghanistan during the Soviet–Afghan War. Kayseri, Van, Amasya, Çiçekdağ, Gaziantep, Tokat, Urfa, and Serinyol received via Adana the Pakistan-based Kazakh, Turkmen, Kirghiz, and Uzbek refugees numbering 3,800 with UNHCR assistance.


title: Kazakhs

text: In 1954 and 1969 Kazakhs migrated into Anatolia's Salihli, Develi and Altay regions. Turkey became home to refugee Kazakhs.


title: Kazakhs

text: One of the most commonly used traditional musical instruments of the Kazakhs is the "dombra", a plucked lute with two strings. It is often used to accompany solo or group singing. Another popular instrument is "kobyz", a bow instrument played on the knees. Along with other instruments, both instruments play a key role in the traditional Kazakh orchestra. A notable composer is Kurmangazy, who lived in the 19th century. After studying in Moscow, Gaziza Zhubanova became the first woman classical composer in Kazakhstan, whose compositions reflect Kazakh history and folklore. A notable singer of the Soviet epoch is Roza Rymbaeva, she was a star of the trans-Soviet-Union scale. A notable Kazakh rock band is Urker, performing in the genre of ethno-rock, which synthesises rock music with the traditional Kazakh music.


title: Lung cancer

text: Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malignant cells that originate as epithelial cells, or from tissues composed of epithelial cells. Other lung cancers, such as the rare sarcomas of the lung, are generated by the malignant transformation of connective tissues (i.e. nerve, fat, muscle, bone), which arise from mesenchymal cells. Lymphomas and melanomas (from lymphoid and melanocyte cell lineages) can also rarely result in lung cancer.


title: Lung cancer

text: In time, this uncontrolled growth can metastasize (spreading beyond the lung) either by direct extension, by entering the lymphatic circulation, or via hematogenous, bloodborne spread – into nearby tissue or other, more distant parts of the body. Most cancers that originate from within the lungs, known as primary lung cancers, are carcinomas. The two main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). The most common symptoms are coughing (including coughing up blood), weight loss, shortness of breath, and chest pains.


title: Lung cancer

text: The vast majority (85%) of cases of lung cancer are due to long-term tobacco smoking. About 10–15% of cases occur in people who have never smoked. These cases are often caused by a combination of genetic factors and exposure to radon gas, asbestos, second-hand smoke, or other forms of air pollution. Lung cancer may be seen on chest radiographs and computed tomography (CT) scans. The diagnosis is confirmed by biopsy, which is usually performed by bronchoscopy or CT-guidance.


title: Lung cancer

text: The major method of prevention is the avoidance of risk factors, including smoking and air pollution. Treatment and long-term outcomes depend on the type of cancer, the stage (degree of spread), and the person's overall health. Most cases are not curable. Common treatments include surgery, chemotherapy, and radiotherapy. NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiotherapy.


title: Lung cancer

text: Worldwide in 2020, lung cancer occurred in 2.2 million people and resulted in 1.8 million deaths. It is the most common cause of cancer-related death in both men and women. The most common age at diagnosis is 70 years. In most countries the five-year survival rate is around 10 to 20%, while in Japan it is 33%, in Israel 27%, and in the Republic of Korea 25%. Outcomes typically are worse in the developing world.


title: Lung cancer

text: Early lung cancer often has no symptoms. When symptoms do arise they are often nonspecific respiratory problems – coughing, shortness of breath, and/or chest pain – that can differ from person to person. Those who experience coughing tend to report either a new cough, or an increase in the frequency or strength of a pre-existing cough. Around a quarter cough up blood, ranging from small streaks in the sputum to large amounts. Around half of those diagnosed with lung cancer experience shortness of breath, while 25–50% experience a dull, persistent chest pain that remains in the same location over time. In addition to respiratory symptoms, some experience systemic symptoms including loss of appetite, weight loss, general weakness, fever, and night sweats.


title: Lung cancer

text: Some less common symptoms suggest tumors in particular locations. Tumors in the thorax can cause breathing problems by obstructing the trachea or disrupting the nerve to the diaphragm, difficulty swallowing by compressing the esophagus, hoarseness by disrupting the nerves of the larynx, and Horner's syndrome by disrupting the sympathetic nervous system. Horner's syndrome is also common in tumors at the top of the lung, known as Pancoast tumors, which also cause shoulder pain that radiates down the little finger-side of the arm as well as destruction of the topmost ribs. Swollen lymph nodes above the collarbone can indicate a tumor that has spread within the chest. Tumors obstructing bloodflow to the heart can cause superior vena cava syndrome, while tumors infiltrating the area around the heart can cause fluid buildup around the heart, arrythmia, and heart failure.


title: Lung cancer

text: Around a third of people diagnosed with lung cancer have symptoms caused by metastases in sites distant from the lung. Lung cancer can metastasize anywhere in the body, with different symptoms depending on the location. Brain metastases can cause headache, nausea, vomiting, seizures, and neurological deficits. Bone metastases can cause pain, bone fractures, and compression of the spinal cord. Metastasis into the bone marrow can deplete blood cells and cause leukoerythroblastosis (immature immune cells in the blood). Liver metastases can cause liver enlargement, pain in the right upper quadrant of the abdomen, fever, and weight loss.


title: Lung cancer

text: Lung tumors also often cause the release of body-altering hormones, which themselves cause unusual symptoms, called paraneoplastic syndromes. Inappropriate hormone release can cause dramatic shifts in concentrations of blood minerals. Most common is hypercalcemia caused by over-production of parathyroid hormone-related protein or parathyroid hormone. Hypercalcemia can manifest as nausea, vomiting, abdominal pain, constipation, increased thirst, frequent urination, and altered mental status. Those with lung cancer also commonly experience hypokalemia due to inappropriate secretion of adrenocorticotropic hormone, as well as hyponatremia due to overproduction of antidiuretic hormone or atrial natriuretic peptide. Around a third of people with lung cancer develop nail clubbing, while up to one in ten experience hypertrophic primary osteoarthropathy. A variety of autoimmune disorders can arise as paraneoplastic syndromes in those with lung cancer, including Lambert–Eaton myasthenic syndrome (which causes muscle weakness), sensory neuropathies, muscle inflammation, brain swelling, and autoimmune deterioration of cerebellum, limbic system, or brainstem. Up to 1 in 12 people with lung cancer have paraneoplastic clotting issues, including migratory venous thrombophlebitis, clots in the heart, and disseminated intravascular coagulation. Paraneoplastic syndromes involving the skin and kidneys are rare, each occurring in up to 1% of those with lung cancer.


title: Lung cancer

text: A person suspected of having lung cancer will first have various imaging tests done to evaluate the presence, extent, and location of tumors. First, many primary care providers perform a chest X-ray to look for a mass inside the lung. The x-ray may reveal an obvious mass, the widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (lung collapse), consolidation (pneumonia), or pleural effusion; however, some lung tumors are not visible by X-ray. Next, many undergo computed tomography (CT) scanning, which can reveal the sizes and locations of tumors.


title: Lung cancer

text: A definitive diagnosis of lung cancer requires a biopsy of the suspected tissue be histologically examined for cancer cells. Bronchoscopic or CT-guided biopsy is often used to sample the tumor for histopathology. Additionally, biopsy material of the original tumor or metastases are often tested for their molecular profile to determine eligibility for targeted therapies. Those who cannot undergo a more invasive biopsy procedure may instead have a liquid biopsy taken (i.e. a sample of some body fluid) which may contain circulating tumor DNA that can be used for molecular testing.


title: Lung cancer

text: Imaging is also used to assess the extent of cancer spread. Positron emission tomography (PET) scanning or combined PET-CT scanning is often used to locate metastases in the body. Since PET scanning cannot be used in the brain, the National Comprehensive Cancer Network recommends magnetic resonance imaging (MRI) – or CT where MRI is unavailable – to scan the brain for metastases in those with NSCLC and large tumors, or tumors that have spread to the nearby lymph nodes. When spread to lymph nodes or to a single site is suspected, the suspected metastasis is often biopsied using a minimally invasive needle biopsy technique – typically using endobronchial ultrasound to guide a bronchoscope equipped with transbronchial needle aspiration. Primary lung cancers most commonly metastasize to the brain, bones, liver, and adrenal glands.


title: Lung cancer

text: Lung cancer can often appear as a solitary pulmonary nodule on a chest radiograph. However, the differential diagnosis is wide and many other diseases can also give this appearance, including metastatic cancer, hamartomas, and infectious granulomas caused by tuberculosis, histoplasmosis, or coccidioidomycosis. Lung cancer can also be an incidental finding, as a solitary pulmonary nodule on a chest radiograph or CT scan done for an unrelated reason. Clinical practice guidelines recommend specific frequencies (suggested intervals of time between tests) for pulmonary nodule surveillance. CT imaging is not suggested to be used for longer or more frequently than indicated in the clinical guidelines, as any additional surveillance exposes people to increased radiation and is costly.


title: Lung cancer

text: At diagnosis, lung cancers are classified based on the type of cells the tumor is derived from; tumors derived from different cells progress and respond to treatment differently. There are two main types of lung cancer, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: small cell lung cancer (SCLC; 15% of lung cancer diagnoses) and non-small-cell lung cancer (NSCLC; 85% of diagnoses). In SCLC, cancerous cells appear small with ill-defined boundaries, not much cytoplasm, many mitochondria, and have distinctive nuclei with granular-looking DNA and no visible nucleoli. Cells contain dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this tumor an endocrine or paraneoplastic syndrome association. Most cases arise in the larger airways (primary and secondary bronchi). NSCLCs comprise a group of three cancer types: adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma. Nearly 40% of lung cancers are adenocarcinomas, which usually come from peripheral lung tissue. Squamous-cell carcinoma causes about 30% of lung cancers. They typically occur close to large airways. A hollow cavity and associated cell death are commonly found at the center of the tumor. Less than 10% of lung cancers are large-cell carcinomas, so named because the cells are large, with excess cytoplasm, large nuclei, and conspicuous nucleoli.


title: Lung cancer

text: Several lung cancer types are subclassified based on the growth characteristics of the cancer cells. Adenocarcinomas are classified as lepidic (growing along the surface of intact alveolar walls), acinar and papillary, or micropapillary and solid pattern. Lepidic adenocarcinomas tend to be least aggressive; micropapillary and solid pattern adenocarcinomas most aggressive.


title: Lung cancer

text: In addition to examining cell morphology, biopsies are also often stained with immunohistochemistry to confirm the diagnosis. SLCL is most often confirmed by the presence of chromogranin, synaptophysin, and CD56. The presence of Napsin-A, TTF-1, CK7, and CK20 help confirm the subtype of lung carcinoma.


title: Lung cancer

text: Around 10% of lung cancers are rarer types. These include mixes of the above subtypes like adenosquamous carcinoma. Rare subtypes include carcinoid tumors, bronchial gland carcinomas, and sarcomatoid carcinomas. A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in females who have not smoked tobacco.


title: Lung cancer

text: Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is one of the factors affecting both the prognosis and the potential treatment of lung cancer.


title: Lung cancer

text: SCLC is typically staged with a relatively simple system; cancers are scored as either "limited stage" or "extensive stage". Around a third of people are diagnosed at the limited stage, meaning cancer is confined to one side of the chest, within the scope of a single tolerable radiotherapy field. The other two thirds are diagnosed at the "extensive stage", with cancer spread to both sides of the chest, or to other parts of the body.


title: Lung cancer

text: NSCLC – and sometimes SCLC – is typically staged with the American Joint Committee on Cancer's Tumor, Node, Metastasis (TNM) staging system. The size and extent of the tumor (T), spread to regional lymph nodes (N), and distant metastases (M) are scored individually, and combined to form "stage groups". Relatively small tumors are designated T1, which are subdivided by size: tumors ≤ 1 centimeter (cm) across are T1a; 1–2 cm T1b; 2–3 cm T1c. Tumors up to 5 cm across, or those that have spread to the visceral pleura (tissue covering the lung) or main bronchi, are desginated T2. T2a designates 3–4 cm tumors; T2b 4–5 cm tumors. T3 tumors are up to 7 cm across, have multiple nodules in the same lobe of the lung, or invade the chest wall, diaphragm (or the nerve that controls it), or area around the heart. Tumors that are larger than 7 cm, have nodules spread in different lobes of a lung, or invade the mediastinum (center of the chest cavity), heart, largest blood vessels that supply the heart, trachea, esophagus, or spine are designated T4. Lymph node staging depends on the extent of local spread: with the cancer metastasized to no lymph nodes (N0), pulmonary or hilar nodes (along the bronchi) on the same side as the tumor (N1), mediastinal or subcarinal lymph nodes (in the middle of the lungs, N2), or lymph nodes on the opposite side of the lung from the tumor (N3). Metastases are staged as no metastases (M0), nearby metastases (M1a; the space around the lung or the heart, or the opposite lung), a single distant metastasis (M1b), or multiple metastases (M1c). These T, N, and M scores are combined to designate a "stage grouping" for the cancer. Cancers limited to smaller tumors are designated stage I. Those with larger tumors or spread to the nearest lymph nodes are stage II. Those with the largest tumors or extensive lymph node spread are stage III. Cancers that have metastasized are stage IV. Each stage is further subdivided based on the combination of T, N, and M scores. Around 40% of those diagnosed with NSCLC have stage IV disease at the time of diagnosis.


title: Lung cancer

text: For both NSCLC and SCLC, the two general types of staging evaluations are clinical staging and surgical staging. Clinical staging is performed before definitive surgery. It is based on the results of imaging studies (such as CT scans and PET scans) and biopsy results. Surgical staging is evaluated either during or after the operation. It is based on the combined results of surgical and clinical findings, including surgical sampling of thoracic lymph nodes.


title: Lung cancer

text: Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the person's performance status. Common treatments for early stage cancers include surgical removal of the tumor, chemotherapy, and radiation therapy. For later stage cancers, chemotherapy and radiation therapy are combined with newer targeted molecular therapies and immune checkpoint inhibitors. All lung cancer treatment regimens are combined with lifestyle changes and palliative care to improve quality of life.


title: Lung cancer

text: Limited-stage SCLC is typically treated with a combination of chemotherapy and radiotherapy. For chemotherapy, the National Comprehensive Cancer Network and American College of Chest Physicians guidelines recommend four to six cycles of a platinum-based chemotherapeutic – cisplatin or carboplatin – combined with either etoposide or irinotecan. This is typically combined with thoracic radiation therapy – 45 Gray (Gy) twice-daily – alongside the first two chemotherapy cycles. First-line therapy causes remission in up to 80% of those who receive it; however most people relapse with chemotherapy-resistant disease. Those who relapse are given second-line chemotherapies. Topotecan and lurbinectedin are approved by the US FDA for this purpose. Irinotecan, paclitaxel, docetaxel, vinorelbine, etoposide, and gemcitabine are also sometimes used, and are similarly efficacious. Prophylactic cranial irradiation can also reduce the risk of brain metastases and improve survival in those with limited-stage disease.


title: Lung cancer

text: Similarly, extensive-stage SCLC is treated first with etoposide along with either cisplatin or carboplatin. Radiotherapy is used only to shrink tumors that are causing particularly severe symptoms. Combining standard chemotherapy with an immune checkpoint inhibitor can improve survival for a minority of those affected, extending the average person's lifespan by around 2 months.


title: Lung cancer

text: For stage I and stage II NSCLC the first line of treatment is often surgical removal of the affected lobe of the lung. For those not well enough to tolerate full lobe removal, a smaller chunk of lung tissue can be removed by wedge resection or segmentectomy surgery. Those with centrally located tumors and otherwise-healthy respiratory systems may have more extreme surgery to remove an entire lung (pneumonectomy). Experienced thoracic surgeons, and a high-volume surgery clinic improve chances of survival. Those who are unable or unwilling to undergo surgery can instead receive radiation therapy. Stereotactic body radiation therapy is best practice, typically administered several times over 1–2 weeks. Chemotherapy has little effect in those with stage I NSCLC, and may worsen disease outcomes in those with the earliest disease. In those with stage II disease, chemotherapy is usually initiated six to twelve weeks after surgery, with up to four cycles of cisplatin – or carboplatin in those with kidney problems, neuropathy, or hearing impairment – combined with vinorelbine, pemetrexed, gemcitabine, or docetaxel.


title: Lung cancer

text: Treatment for those with stage III NSCLC depends on the nature of their disease. Those with more limited spread may undergo surgery to have the tumor and affected lymph nodes removed, followed by chemotherapy and potentially radiotherapy. Those with particularly large tumors (T4) and those for whom surgery is impractical are treated with combination chemotherapy and radiotherapy along with the immunotherapy durvalumab. Combined chemotherapy and radiation enhances survival compared to chemotherapy followed by radiation, though the combination therapy comes with harsher side effects.


title: Lung cancer

text: Those with stage IV disease are treated with combinations of pain medication, radiotherapy, immunotherapy, and chemotherapy. Many cases of advanced disease can be treated with targeted therapies depending on the genetic makeup of the cancerous cells. Up to 30% of tumors have mutations in the "EGFR" gene that result in an overactive EGFR protein; these can be treated with EGFR inhibitors osimertinib, erlotinib, gefitinib, afatinib, or dacomitinib – with osimertinib known to be superior to erlotinib and gefitinib, and all superior to chemotherapy alone. Up to 7% of those with NSCLC harbor mutations that result in hyperactive ALK protein, which can be treated with ALK inhibitors crizotinib, or its successors alectinib, brigatinib, and ceritinib. Those treated with ALK inhibitors who relapse can then be treated with the third-generation ALK inhibitor lorlatinib. Up to 5% with NSCLC have overactive MET, which can be inhibited with MET inhibitors capmatinib or tepotinib. Targeted therapies are also available for some cancers with rare mutations. Cancers with hyperactive BRAF (around 2% of NSCLC) can be treated by dabrafenib combined with the MEK inhibitor trametinib; those with activated ROS1 (around 1% of NSCLC) can be inhibited by crizotinib, lorlatinib, or entrectinib; overactive NTRK (<1% of NSCLC) by entrectinib or larotrectinib; active RET (around 1% of NSCLC) by selpercatinib.


title: Lung cancer

text: People whose NSCLC is not targetable by current molecular targeted therapies instead can be treated with combination chemotherapy plus immune checkpoint inhibitors, which prevent cancer cells from inactivating immune T cells. The chemotherapeutic agent of choice depends on the NSCLC subtype: cisplatin plus gemcitabine for squamous cell carcinoma, cisplatin plus pemetrexed for non-squamous cell carcinoma. Immune checkpoint inhibitors are most effective against cancers that express the protein PD-L1, but are sometimes effective in those that do not. Treatment with pembrolizumab, atezolizumab, or combination nivolumab plus ipilimumab are all superior to chemotherapy alone against tumors expressing PD-L1. Those who relapse on the above are treated with second-line chemotherapeutics docetaxel and ramucirumab.


title: Lung cancer

text: Several treatments can be provided via bronchoscopy for the management of airway obstruction or bleeding. If an airway becomes obstructed by cancer growth, options include rigid bronchoscopy, balloon bronchoplasty, stenting, and microdebridement. Laser photosection involves the delivery of laser light inside the airway via a bronchoscope to remove the obstructing tumor.


title: Lung cancer

text: Integrating palliative care (i.e. medical care focused on improving symptoms and lessening discomfort) into lung cancer treatment from the time of diagnosis improves the survival time and quality of life of those with lung cancer. Particularly common symptoms of lung cancer are shortness of breath and pain. Supplemental oxygen, improved airflow, re-orienting an effected person in bed, and low-dose morphine can all improve shortness of breath. Other causes of lung cancer-associated shortness of breath can be treated directly, such as antibiotics for a lung infection, diuretics for pulmonary edema, benzodiazepines for anxiety, and steroids for airway obstruction. Up to 92% of those with lung cancer report pain, either from tissue damage at the tumor site(s) or nerve damage. The World Health Organization (WHO) has developed a three-tiered system for managing cancer pain. For those with mild pain (tier one), the WHO recommends acetominophen or a nonsteroidal anti-inflammatory drug. Around a third of people experience moderate (tier two) or severe (tier three) pain, for which the WHO recommends opioid painkillers. Opioids are typically effective at easing nociceptive pain (pain caused by damage to various body tissues). Opioids are occasionally effective at easing neuropathic pain (pain cauesd by nerve damage); Neuropathic agents such as anticonvulsants, tricyclic antidepressants, and serotonin–norepinephrine reuptake inhibitors, are often used to ease neuropathic pain, either alone or in combination with opioids.


title: Lung cancer

text: For both NSCLC and SCLC patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy). With adequate physical fitness maintaining chemotherapy during lung cancer palliation offers 1.5 to 3 months of prolongation of survival, symptomatic relief, and an improvement in quality of life, with better results seen with modern agents.


title: Lung cancer

text: Palliative care when added to usual cancer care benefits people even when they are still receiving chemotherapy. These approaches allow additional discussion of treatment options and provide opportunities to arrive at well-considered decisions. Palliative care may avoid unhelpful but expensive care not only at the end of life, but also throughout the course of the illness. For individuals who have more advanced disease, hospice care may also be appropriate.


title: Lung cancer

text: The most effective intervention for avoiding death from lung cancer is to stop smoking; even people who already have lung cancer are encouraged to stop smoking. There is no clear evidence which smoking cessation program is most effective for people who have been diagnosed with lung cancer.


title: Lung cancer

text: Some weak evidence suggests that certain supportive care interventions (noninvasive) that focus on well-being for people with lung cancer may improve quality of life. Interventions such as nurse follow-ups, psychotherapy, psychosocial therapy, and educational programs may be beneficial, however, the evidence is not strong (further research is needed). Counseling may help people cope with emotional symptoms related to lung cancer. Reflexology may be effective in the short-term, however more research is needed. No evidence has been found to suggest that nutritional interventions or exercise programs for a person with lung cancer result in an improvement in the quality of life that are relevant or last very long.


title: Lung cancer

text: Exercise training may benefit people with NSCLC who are recovering from lung surgery. In addition, exercise training may benefit people with NSCLC who have received radiotherapy, chemotherapy, chemoradiotherapy, or palliative care. Exercise training before lung cancer surgery may also improve outcomes. It is unclear if exercise training or exercise programs are beneficial for people who have advanced lung cancer. A home-based component in a personalized physical rehabilitation program may be useful for recovery. It is unclear if home-based prehabilitation (before surgery) leads to less adverse events or hospitalization time. Physical rehabilitation with a home-based component may improve recovery after treatment and overall lung health.


title: Lung cancer

text: Around 19% of people diagnosed with lung cancer survive five years from diagnosis. Five-year survival is higher in women (22%) than men (16%); women tend to be diagnosed with less-advanced disease, and have better outcomes than men diagnosed at the same stage. In England and Wales, between 2013 and 2017, overall five-year survival for lung cancer was estimated at 13.8%. Outcomes are generally worse in the developing world. In the US, people with medical insurance are more likely to have a better outcome.


title: Lung cancer

text: Survival for lung cancer falls as the stage at diagnosis becomes more advanced; the English data suggest that around 70% of patients survive at least a year when diagnosed at the earliest stage, but this falls to just 14% for those diagnosed with the most advanced disease (stage IV).


title: Lung cancer

text: SCLC is particularly aggressive. Most people treated for SCLC relapse and eventually develop chemotherapy-resistant cancer. The average person diagnosed with SCLC at the limited stage survives 12–20 months from diagnosis; the average person diagnosed at the extensive stage survives around 12 months. 10–15% of people with SCLC survive 5 years after diagnosis. Those with limited stage SCLC that goes into complete remission after chemotherapy and radiotherapy have a 50% chance of brain metastases developing within the next two years – a chance reduced by prophylactic cranial irradiation.


title: Lung cancer

text: For NSCLC, the best prognosis is achieved with complete surgical resection of stage-IA disease, with up to 70% five-year survival. The prognosis of patients with NSCLC improved significantly in the last years with the introduction of immunotherapy. 68–92% of those diagnosed with stage I NSCLC survive at least 5 years after diagnosis, as do 53–60% of those diagnosed with stage II NSCLC.


title: Lung cancer

text: Several personal and disease factors are associated with improved outcomes. Those diagnosed at an earlier disease stage tend to have better prognoses, as do those diagnosed at a younger age. Those who smoke or experience weight loss as a symptom tend to have worse outcomes. Large/active metastases (by PET scan) and tumor mutations in "KRAS" are associated with reduced survival.


title: Lung cancer

text: Cancer develops after genetic damage to DNA and epigenetic changes. Those changes affect the cell's normal functions, including cell proliferation, programmed cell death (apoptosis), and DNA repair. As more damage accumulates, the risk for cancer increases.


title: Lung cancer

text: Tobacco smoking is by far the major contributor to lung cancer, causing 80% to 90% of cases. Across the developed world, 90% of lung cancer deaths in men and 70% of those in women during 2000 were attributed to smoking. Cigarette smoke contains at least 73 known carcinogens, including benzo["a"]pyrene, NNK, 1,3-butadiene, and a radioactive isotope of polonium – polonium-210. Vaping may be a risk factor for lung cancer, but less than that of cigarettes, and further research is necessary due to the length of time it can take for lung cancer to develop following an exposure to carcinogens.


title: Lung cancer

text: Being around tobacoo smoke – called passive smoking – can also cause lung cancer. Living with a tobacco smoker increaes one's risk of developing lung cancer by 24%. An estimated 17% of lung cancer cases in those who do not smoke are caused by high levels of environmental tobacco smoke.


title: Lung cancer

text: Cannabis smoke contains many of the same carcinogens as those found in tobacco smoke, but the effect of smoking cannabis on lung cancer risk is not clear.


title: Lung cancer

text: Exposure to a variety of other toxic chemicals – typically encountered in certain occupations – are associated with an increased risk of lung cancer. In all, occupational exposures to carcinogens are estimated to cause 9–15% of lung cancers. A prominent example is asbestos, which causes lung cancer either directly or indirectly by inflamming the lung. Exposure to all commercially available forms of asbestos increase cancer risk, and cancer risk increases with time of exposure. Asbestos and cigarette smoking increase risk synergestically – i.e. the risk of someone who smokes and has asbestos exposure dying from lung cancer is much higher than would be expected from adding the two risks together. Similarly, exposure to radon, a naturally occurring breakdown product of the Earth's uranium, is associated with increased lung cancer risk. This is particularly true in underground miners, who have the greatest exposure; but also in indoor air in residential spaces. Like asbestos, cigarette smoking and radon exposure increase risk synergistically. Radon exposure is responsible for between 3% and 14% of lung cancer cases.


title: Lung cancer

text: Several other chemicals encountered in various occupations are also associated with increased lung cancer risk including arsenic used in wood preservation, pesticide application, and some ore smelting; ionizing radiation encountered during uranium mining; vinyl chloride in papermaking; beryllium in jewelers, ceramics workers, missile technicians, and nuclear reactor workers; chromium in stainless steel production, welding, and hide tanning; nickel in electroplaters, glass workers, metal workers, welders, and those who make batteries, ceramics, and jewelry; and diesel exhaust encountered by miners.


title: Lung cancer

text: Outdoor air pollutants, especially chemicals released from the burning of fossil fuels, increase the risk of lung cancer. Fine particulates (PM) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with a slightly increased risk. For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%. Outdoor air pollution is estimated to cause 1–2% of lung cancers.


title: Lung cancer

text: Indoor air pollution from burning wood, charcoal, or crop residue for cooking and heating has also been linked to an increased risk of developing lung cancer. The International Agency for Research on Cancer has classified emission from household burning of coal and biomass as "carcinogenic" and "probably carcinogenic" respectively. This risk affects about 2.4 billion people worldwide, and it is believed to result in 1.5% of lung cancer deaths.


title: Lung cancer

text: About 8% of lung cancer cases are caused by inherited (genetic) factors. In relatives of people who are diagnosed with lung cancer, the risk is doubled, likely due to a combination of genes. Polymorphisms on chromosomes 5, 6, and 15 have been identified and are associated with an increased risk of lung cancer. Single-nucleotide polymorphisms of the genes encoding the nicotinic acetylcholine receptor (nAChR) – "CHRNA5", "CHRNA3", and "CHRNB4" – are of those associated with an increased risk of lung cancer, as well as "RGS17" – a gene regulating G-protein signaling. Newer genetic studies, have identified 18 susceptibility loci achieving genome-wide significance. These loci highlight a heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, again identifying the cholinergic nicotinic receptors, e.g. CHRNA2.


title: Lung cancer

text: Similar to many other cancers, lung cancer is initiated by either the activation of oncogenes or the inactivation of tumor suppressor genes. Carcinogens cause mutations in these genes that induce the development of cancer.


title: Lung cancer

text: Mutations in the "K-ras" proto-oncogene contribute to roughly 10–30% of lung adenocarcinomas. Nearly 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase fusion gene. The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion. Mutations and amplification of EGFR are common in NSCLC, and they provide the basis for treatment with EGFR inhibitors. "Her2/neu" is affected less frequently. Other genes that are often mutated or amplified include "c-MET", "NKX2-1", "LKB1", "PIK3CA", and "BRAF".


title: Lung cancer

text: Importantly, cancer cells develop resistance to oxidative stress, which enables them to withstand and exacerbate inflammatory conditions that inhibit the activity of the immune system against the tumor.


title: Lung cancer

text: The cell lines of origin are not fully understood. The mechanism may involve the abnormal activation of stem cells. In the proximal airways, stem cells that express keratin 5 are more likely to be affected, typically leading to squamous-cell lung carcinoma. In the middle airways, implicated stem cells include club cells and neuroepithelial cells that express club-cell secretory protein. SCLC may originate from these cell lines or neuroendocrine cells, and it may express CD44. Metastasis of lung cancer requires transition from epithelial to mesenchymal cell type. This may occur through the activation of signaling pathways such as Akt/GSK3Beta, MEK-ERK, Fas, and Par6.


title: Lung cancer

text: Those who smoke can reduce their lung cancer risk by quitting smoking – the risk reduction is greater the longer a person goes without smoking. Self-help programs tend to have little influence on success of smoking cessation, whereas combined counseling and pharmacotherapy improve cessation rates. The U.S. FDA has approved antidepressant therapies and the nicotine replacement varenicline as first-line therapies to aid in smoking cessation. Clonidine and nortriptyline are recommended second-line therapies.


title: Lung cancer

text: While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process.


title: Lung cancer

text: Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries. Bhutan has had a complete smoking ban since 2005 while India introduced a ban on smoking in public in October 2008. The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where instituted.


title: Lung cancer

text: Some forms of population screening can allow for earlier detection and treatment of lung cancer cases, reducing deaths from lung cancer. In some trials, screening programs providing low-dose CT scans of individuals at high risk for lung cancer (i.e. people who smoke tobacco and are aged 55 to 74) reduced overall lung cancer mortality. The United States Preventive Services Task Force recommends yearly screening using low-dose CT in those who have a total smoking history of at least 30 pack-years and are between 55 and 80 years old.


title: Lung cancer

text: The long-term use of supplemental vitamin A, B vitamins, vitamin D or vitamin E does not reduce the risk of lung cancer. Vitamin C supplementation might reduce the risk of lung cancer. Some studies have found vitamins A, B, and E may increase the risk of lung cancer in those who have a history of smoking.


title: Lung cancer

text: Some studies suggest that people who eat food with a higher proportion of vegetables and fruit tend to have a lower risk, but this may be due to confoundingwith the lower risk actually due to the association of a high fruit and vegetables diet with less smoking. Several rigorous studies have not demonstrated a clear association between diet and lung cancer risk, although meta-analysis that accounts for smoking status may show benefit from a healthy diet.


title: Lung cancer

text: Worldwide, lung cancer is the most diagnosed type of cancer, and the leading cause of cancer death. In 2020, 2.2 million new cases were diagnosed, and 1.8 million people died from lung cancer, representing 18% of all cancer deaths. Lung cancer deaths are expected to rise globally to nearly 3 million annual deaths by 2035, due to high rates of tobacco use and aging populations. Lung cancer is rare in those younger than 40; from there cancer rates increase with age, stabilizing around age 80. The median age of a person diagnosed with lung cancer is 70; the median age of death is 72.


title: Lung cancer

text: Lung cancer incidence varies dramatically by geography and sex, with the highest rates in Micronesia, Polynesia, Europe, Asia, and North America; and lowest rates in Africa and Central America. Globally, around 8% of men and 6% of women develop lung cancer in their lifetimes. However, the ratio of lung cancer cases in men to women varies dramatically by geography, as high as nearly 12:1 in Belarus, to 1:1 in Brazil, likely due to differences in smoking patterns. In the United States, lung cancer remains the most common cause of cancer deaths, despite a nearly 50% decrease in the death rate from its peak in 1990. Lung cancer is the third-most common cancer in the UK (47,968 people were diagnosed with the disease in 2017), and it is the most common cause of cancer-related death (around 34,600 people died in 2018).


title: Lung cancer

text: In the US, lung cancer rates also vary by racial and ethnic group, with the highest rates in African Americans, and the lowest rates in Hispanics, Native Americans and Asian Americans. Also in the US, military veterans have a 25–50% higher rate of lung cancer primarily due to higher rates of smoking. During World War II and the Korean War, asbestos also played a role, and Agent Orange may have caused some problems during the Vietnam War.


title: Lung cancer

text: Lung cancer risk is dramatically influenced by environmental exposure, namely cigarette smoking, as well as occupational risks in mining, shipbuilding, petroleum refining, and occupations that involve asbestos exposure. 85–90% of lung cancer cases are in people who have smoked cigarettes, and 15% of smokers develop lung cancer. People who have a long history of smoking have the highest risk of developing lung cancer, with the risk increasing with duration of smoking. The incidence in men rose until the mid-1980s, and has declined since then. In women, the incidence rose until the late 1990s, and has since been stable. Non-smokers' risk of developing lung cancer is also influenced by tobacco smoking; secondhand smoke (i.e. being around tobacco smoke) increases risk of developing lung cancer around 30%, with risk correlated to duration of exposure.


title: Lung cancer

text: For every 3–4 million cigarettes smoked, one lung cancer death can occur. The influence of "Big Tobacco" plays a significant role in smoking. Young nonsmokers who see tobacco advertisements are more likely to smoke. The role of passive smoking is increasingly being recognized as a risk factor for lung cancer, resulting in policy interventions to decrease the undesired exposure of nonsmokers to others' tobacco smoke.


title: Lung cancer

text: From the 1960s, the rates of lung adenocarcinoma started to rise in relation to other kinds of lung cancer, partially due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However, the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise. Rates of lung adenocarcinoma continues to rise.


title: Lung cancer

text: Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761. Different aspects of lung cancer were described further in 1810. Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 10–15% by the early 1900s. Case reports in the medical literature numbered only 374 worldwide in 1912, but a review of autopsies showed the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952. In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer, which led to an aggressive antismoking campaign. The British Doctors' Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking. As a result, in 1964, the Surgeon General of the United States recommended smokers should stop smoking.


title: Lung cancer

text: The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and these mines are rich in uranium, with its accompanying radium and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium. Radon was confirmed as a cause of lung cancer in the 1960s.


title: Lung cancer

text: The first successful pneumonectomy for lung cancer was performed in 1933. Palliative radiotherapy has been used since the 1940s. Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early-stage lung cancer, but who were otherwise unfit for surgery. In 1997, CHART was seen as an improvement over conventional radical radiotherapy. With SCLC, initial attempts in the 1960s at surgical resection and radical radiotherapy were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.


title: Lung cancer

text: The search for new treatment options continues. Many clinical trials involving radiotherapy, surgery, EGFR inhibitors, microtubule inhibitors and immunotherapy are currently underway.


title: Lung cancer

text: Research directions for lung cancer treatment include immunotherapy, which encourages the body's immune system to attack the tumor cells, epigenetics, and new combinations of chemotherapy and radiotherapy, both on their own and together. Many of these new treatments work through immune checkpoint blockade, disrupting cancer's ability to evade the immune system.


title: Lung cancer

text: Ipilimumab blocks signaling through a receptor on T cells known as CTLA-4, which dampens down the immune system. It has been approved by the US Food and Drug Administration for treatment of melanoma, and is undergoing clinical trials for both NSCLC and SCLC.


title: Lung cancer

text: Other immunotherapy treatments interfere with the binding of programmed cell death 1 (PD-1) protein with its ligand PD-1 ligand 1 (PD-L1), and have been approved as first- and subsequent-line treatments for various subsets of lung cancers. Signaling through PD-1 inactivates T cells. Some cancer cells appear to exploit this by expressing PD-L1 in order to switch off T cells that might recognise them as a threat. Monoclonal antibodies targeting both PD-1 and PD-L1, such as pembrolizumab, nivolumab, atezolizumab, and durvalumab are currently in clinical trials for treatment for lung cancer.


title: Lung cancer

text: Epigenetics is the study of small molecular modificationsor "tags"that bind to DNA and modify gene expression levels. Targeting these tags with drugs can kill cancer cells. Early-stage research in NSCLC using drugs aimed at epigenetic modifications shows that blocking more than one of these tags can kill cancer cells with fewer side effects. Studies also show that giving people these drugs before standard treatment can improve its effectiveness. Clinical trials are underway to evaluate how well these drugs kill lung cancer cells in humans. Several drugs that target epigenetic mechanisms are in development. Histone deacetylase inhibitors in development include valproic acid, vorinostat, belinostat, panobinostat, entinostat, and romidepsin. DNA methyltransferase inhibitors in development include decitabine, azacytidine, and hydralazine.


title: Lung cancer

text: The TRACERx project is looking at how NSCLC develops and evolves, and how these tumors become resistant to treatment. The project will look at tumor samples from 850 people with NSCLC at various stages including diagnosis, after first treatment, post-treatment, and relapse. By studying samples at different points of tumor development, the researchers hope to identify the changes that drive tumor growth and resistance to treatment. The results of this project will help scientists and doctors gain a better understanding of NSCLC and potentially lead to the development of new treatments for the disease.


title: Lung cancer

text: For lung cancer cases that develop resistance to epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors, new drugs are in development. EGFR inhibitors include erlotinib, gefitinib, afatinib and icotinib (the last one is only available in China). An alternative signaling pathway, c-Met, can be inhibited by tivantinib and onartuzumab. New ALK inhibitors include crizotinib and ceritinib. If the MAPK/ERK pathway is involved, the BRAF kinase inhibitor dabrafenib and the MAPK/MEK inhibitor trametinib may be beneficial.