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O THE R GEN ET IC M U T A TIONS AND BR E AST CANCER

STK 1 1

nan nan

Pe u tz – Je ghe r s synd r o m e (P J S) is a rare a u t o s o mal do mi n a n t g astr o i n test inal h ama r t o m a t ous po l ypos i s synd r o me . It is estimate d t h at t h e i n ci d e n ce is a pprox im a t e l y 1 i n 150,000 i n N o rt h America a nd W ester n E u r op e

O THE R GEN ET IC M U T A TIONS AND BR E AST CANCER

STK 1 1

nan nan

O THE R GEN ET IC M U T A TIONS AND BR E AST CANCER

STK 1 1

nan nan

PJS is c ha r ac t e ri zed by t he dev el op me n t o f Pe u tz – Je gh ers po l yp s i n t h e i n testi n e i n con j unc ti on w it h p i g me n tati on ( b r o w n o r b l u is h s po ts) ar ound a nd i n si de t he m ou t h, nose an d li p s , a nd p eria n al area , as well as o t h er pa r ts of t h e bod y . T hese l es i ons a r e o fte n m o st p r o mi n e n t i n c h il dhood a nd fa de w it h a ge. M o st f a mili es w it h P J S hav e m u tati on s i n t h e S TK 1 1 g e n e , alt hough t his g e n e do e s no t exp l a i n a ll i nhe rite d cases o f PJS as well as ma ny sim p le x cases . T he lif e tim e ri sk o f b reast ca n cer i n females is re po rte d i n a wi de r a ng e , w it h t he m os t cons i s t en t ris k s b ei ng i n t h e 30 % t o 50 % ra ng e ,

O THE R GEN ET IC M U T A TIONS AND BR E AST CANCER

STK 1 1

nan nan

O THE R GEN ET IC M U T A TIONS AND BR E AST CANCER

STK 1 1

nan nan

O t h e r c ance r s t ha t can be see n i n PJS i n cl ud e ca n cers o f t h e c o l on, p a n c r ea s, s t o m ach, ova r y , s mall i n testi n e , l ung, cer v i x, testes , u ter u s , a nd es oph a gus. Consensus d i agno stic criteria were pub lis h e d i n 2010 a nd ar e liste d i n

O THE R GEN ET IC M U T A TIONS AND BR E AST CANCER

CDH1

nan nan

CDH1

O THE R GEN ET IC M U T A TIONS AND BR E AST CANCER

CDH1

nan nan

H e r e d it a r y d i f f use gas tri c canc er is a rare a u t o s o mal do mi n a n t h ere d itary s yndro m e cha r ac t e ri zed by d i f f u se ( o r si gn et ri ng cell p at ho l ogy ) st o ma ch ca n ce r . T he i nc i dence o f t h i s s ynd r o me is no t well kno w n bu t li k el y t o be r a r e . The lif e tim e ri sk o f s t om ac h ca n cer is t hough t t o b e a pp r ox imatel y 80% c o m pa r ed w it h <1 % i n the g e n eral popu lati on . , T h e sec ond m o s t c o mm on cance r i n f a mili es wi t h t h is s ynd r o me is l obu lar b reast ca n ce r , with a li f etim e ri sk o f abou t 40 % i n w o me n . Cleft li p a nd p alate h a v e al so b ee n r ep o rt ed i n so m e f a mili e s . T h e I n ter n ati on al Gastric Ca n cer Li nkage C on s or t iu m pub li shed c li n i ca l criteria i n 2010, s ho w n i n T he

O THE R GEN ET IC M U T A TIONS AND BR E AST CANCER

CDH1

nan nan

i n ci d e n ce o f CDH1 m u t a ti on s i n l obu lar b reast ca n cer cases is t hough t t o be l ow i n t he absence o f a f a mil y h ist o r y o f g astric ca n ce r

MO D ER A T E - A N D LO W -PEN E TRANCE BREA S T CANC E R GE NES

nan nan

MO D ER A T E - A N D LO W -PEN E TRANCE BREA S T CANC E R GE NES

MO D ER A T E - A N D LO W -PEN E TRANCE BREA S T CANC E R GE NES

nan nan

Th e r e a r e seve r a l genes t ha t h a v e alrea dy b ee n d escri b e d i n families wit h br east c ance r i nc l ud i ng CH EK 2 a nd A TM . T h e ris k o f b reast ca n cer ass o ciate d w it h a lt e r a ti ons i n t h ese g e n es is t hough t t o b e l o wer t h a n wit h t r a d iti ona l he r ed it a r y b r eas t c a n cer s ynd r o mes; o t h er fact o rs are li k el y t o i n te r act w it h t he e f f ec t s o f ch a ng es i n t h ese g e n es a nd res u lt i n a m o re m od e r at e i nc r ease i n ri sk f o r b reast ca n ce r . Rece n tl y , a U S g r oup pub lis h e d a st udy on 12 g e n es li nk e d t o h ere d it a r y ov a r ia n cance r , wh i ch a r e a l so b ei ng a n al y ze d i n families wit h h ere d itar y br east c ance r Mo r e l abo rat o ries are b e g i nn i ng t o o f fer g e n etic testi ng for p a n el s o f genes t ha t a r e i mpo rta n t i n DNA re p air p at h wa y s T h ere ar e se v e r al ca t ego ri es o f t hese gen es . 1. Cate go r y 1—genes f unc ti on all y relate d t o BRCA 1 a nd BRCA 2 ( A TM , BAR D 1 , CH E K 2 , MRE 1 1 A , NBN , RAD 5 0 , RAD 51 D ) • A T M ( a t ax i a t e l ang i ec t a sia m u tate d ) • BA R D1 ( BR C A 1 - assoc i a te d RING do mai n 1 ) • CHE K2 ( ce ll cyc l e checkpo i n t k i n ase 2 ) • MR E 1 1 A (m e i o ti c r ecomb i n ati on 1 1 ho m o l og A) • N BN ( n i b ri n ; aka N B S 1 ) • RAD50 • RAD51D 2. Cate go r y 2— ( o t he r) gene s i n t h e Fa n c on i a n emia p at h wa y t h at i n crea se br east cance r ri sk ( BRIP 1 , P ALB 2 , RAD 51 C ) • BR IP 1 ( BR C A -i n t e r ac ti ng p r o tei n C-termi n al h elicase 1 ; F ANCJ ) • P A LB 2 ( pa rt ne r and l ocal izer o f BRCA 2 ; F ANCN ) • RAD51C ( F A NCO )

MO D ER A T E - A N D LO W -PEN E TRANCE BREA S T CANC E R GE NES

nan nan

3. Cate go r y 3—genes i nvo l v e d i n h ere d itar y c o l o rectal ca n cer ( MLH 1 , MSH2 , M SH6 , PM S2 , EPCAM , MYH ) F or ma ny o f t he genes i n ca t ego ries 1 a nd 2, ris k s o f b reast ca n cer are not w ell d e fined, and it i s unc l ea r if w o me n w ho test n e g ati v e f o r a m u tati on t h at w as f ound i n an a f f ec t ed relati v e (“tr u e n e g ati v es”) are reall y at g e ne r al popu lati on ri sk.

MO D ER A T E - A N D LO W -PEN E TRANCE BREA S T CANC E R GE NES

L ynch Synd r ome and MYH-Associated Polyposis

nan nan

L ynch Synd r ome and MYH-Associated Polyposis

MO D ER A T E - A N D LO W -PEN E TRANCE BREA S T CANC E R GE NES

L ynch Synd r ome and MYH-Associated Polyposis

nan nan

L yn c h s ynd r o m e (LS) i s t he m o st c o mm on h ere d itar y f o rm o f c o l o rectal ca n ce r , accoun ti ng f o r abou t 2% t o 3 % o f c o l o rectal ca n cer cases . It is ca u se d by m u t a ti ons i n genes i nvo l v e d i n DNA mismatc h re p ai r , i n cl ud i ng M L H1 , M SH2 , M SH6 , PM S2 , a nd, i nd irectl y , EPCAM . LS is t yp icall y c h a r acteri zed by t he deve l op me n t o f relati v el y earl y - on set c o l o rectal a nd u te r i n e cance r; ri sks f o r o t he r ca n cers i n cl ud i ng st o mac h ca n ce r , ca n cer o f t h e smal l i n t es ti ne, panc r ea ti c ca n ce r , se b ace ou s carci no mas , ov aria n ca n ce r , and cance r s o f t he u ri n ar y c o llecti ng tract . Rarel y , b rai n t u m o rs ar e t hough t t o be i nc r eased . Mo st st ud ies h a v e no t s ho w n a si gn ifica n t i n c r ease i n b r eas t cance r ri sk f o r MMR m u tati on carriers v ers u s non ca rr i e r s, a lt hough a m o r e rece n t article st udy i ng a c oho rt o f LS f amilies p r ospec ti ve l y d i d sho w a f ou rf o l d i n crease i n b reast ca n cer ris k .

MO D ER A T E - A N D LO W -PEN E TRANCE BREA S T CANC E R GE NES

L ynch Synd r ome and MYH-Associated Polyposis

nan nan

MO D ER A T E - A N D LO W -PEN E TRANCE BREA S T CANC E R GE NES

L ynch Synd r ome and MYH-Associated Polyposis

nan nan

I t is clear t ha t de f ec ti ve mi s matc h re p air ca n b e see n i n s o me b reast ca nce r s i n wo m en fr o m LS f a mili es . W h et h er t h ere is a tr u e i n crease i n ris k ( a nd t h e m agn it ude o f t h i s ri sk ) remai n s t o b e see n. M Y H - assoc i a t ed po l ypos i s (MAP) is t h e lesser kno w n o f t h e a d e no mat ous po l ypos i s synd r o mes ( v ers u s familial a d e no mat ou s po l ypo s is ) . MY H i s i nvo l ved i n b ase e x cisi on re p air; wit hou t MYH , ox i d ati ve DNA da m age l eads t o t h e f o rmati on o f 8 - oxo -G , w h ic h mis p a i r s w it h a den i ne. T h i s l eads t o an i n crease i n G:C > T :A tra n s v ersi on s i n AP C a nd o t he r genes MA P i s asso ciate d wit h a n atte nu ate d ph e no t yp e; fe we r a d e no ma s ( gene r a ll y i n t he r ang e o f 10 t o 100 ) a nd a mi x t u re o f po l yp t ypes ( se rr ate d adeno m as, hype r p l a stic po l yp s) a nd duod e n al po l yp s are o fte n

MO D ER A T E - A N D LO W -PEN E TRANCE BREA S T CANC E R GE NES

L ynch Synd r ome and MYH-Associated Polyposis

nan nan

see n E x tr a i n t es ti na l m an ifestati on s , i n cl ud i ng b reast ca n ce r , h a v e been r e por te d i n MA P . Howe ve r , MYH do es no t a pp ear t o b e a c o mm on ca u se of b r eas t cance r .

CONC L USION

nan nan

CONC L USION

CONC L USION

nan nan

Th is c hap t e r has p r ov i ded a s y nop sis o f t h e g e n es li nk e d t o t h e m o st wel l - d e f i n e d synd r o m es assoc i a t ed wit h b reast ca n cer a nd a n i n tr odu cti on t o br east c ance r gene pane l s. It i s im po rta n t f o r cli n icia n s t o b e a b le t o i d e nti f y t h e clas s i c b r eas t cance r synd r o mes , kno w t h e rele v a n t g e n es , a nd und e r sta nd t he m ed i ca l m anag eme n t a nd p s y c ho s o cial iss u es ass o ciate d w it h t h e synd r o m es. T he adv e n t o f w ho le g e no me se qu e n ci ng a nd t h e a b ilit y t o ana l yze t he es tim a t e d 22,000 g e n es i n t h e hu ma n g e no me wit h c h ea p a nd e f fi c i en t t echno l ogy b ri ng t h e hop e t h at all o f t h e g e n es i nvo l ved i n h e r e d it a r y and f a mili a l b r e ast ca n cer will b e f ound. H o we v e r , ma k i ng this i nfor ma t i on c li n i ca ll y r e l evan t will re qu ire m u c h m o re researc h. El u ci d a ting t h e i n te rac ti on o f m u t a ti ons i n t h ese g e n es wit h m od if y i ng fact o rs c ou l d h el p cla r if y ri sks i n f a mili es and lea d t o tar g ete d scree n i ng a nd p re v e n ti on meas ur e s. It i s c l ea r t ha t genet ic testi ng will b ec o me m o re c o m p licate d ove r time a nd t ha t t he i n t e r p r e t a ti on o f test res u lts will re qu ire c on ti nu i ng e du cati o n and expe rti se i n t he fiel d.

CONC L USION

nan nan

Arun B, Bayraktar S, Liu DD, et al. Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: A single-institution experience. J Clin Oncol 20 1 1;29:3739–3746. Berry DA, Iversen ES J r , Gudbjartsson D F , et al. BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes. J Clin Oncol 2002;20:2701–2712. T yrer J, Du f fy S W , Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med 2004;23: 1 11 1– 1 130. Couch FJ, DeShano ML, Blackwood MA, et al. BRCA1 mutations in women attending clinics that evaluate the risk of breast cance r . N Engl J Med 1997;336:1409–1415. Shattuck-Eidens D, Oliphant A, McClure M, et al. BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. JAMA 1997;278:1242–1250. Kang HH, W illiams R, Leary J, et al. Evaluation of models to predict BRCA germline mutations. Br J Cancer 2006;95:914–920. Barcenas CH, Hosain GM, Arun B, et al. Assessing BRCA carrier probabilities in extended families. J Clin Oncol 2006;24:354–360. James P A, Doherty R, Harris M, et al. Optimal selection of individuals for BRCA mutation testing: A comparison of available methods. J Clin Oncol 2006;24:707–715. Saslow D, Castle PE, Cox J T , et al. American Cancer Society Guideline for human papillomavirus (HPV) vaccine use to prevent cervical cancer and its precursors. CA Cancer J Clin 2007;57:7–28. King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003;302:643–646. Ozçelik H, Schmocker B, Di Nicola N, et al. Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients. Nat Genet 1997;16:17–18. Antoniou A, Pharoah PD, Narod S, et al. A verage risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 2003;72: 1 1 17– 1 130. Risch HA, McLaughlin JR, Cole DE, et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cance r . Am J Hum Genet 2001;68:700–710. The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999;91:1310–1316. Thompson D, Easton D F . Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 2002;94:1358–1365. Thompson D, Easton D. V ariation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 2001;68:410–419. van Asperen CJ, Brohet RM, Meijers-Heijboer EJ, et al. Cancer risks in BRCA2 families: Estimates for sites other than breast and ovar y . J Med Genet 2005;42:7 1 1–719. Hartmann LC, Sellers T A, Schaid DJ, et al. E f ficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 2001;93:1633–1637. Rebbeck TR, Friebel T , L ynch H T , et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: The PROSE Study Group. J Clin Oncol 2004;22:1055– 1062.

CONC L USION

nan nan

Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2001;345:159–164. Robson M, Svahn T , McCormick B, et al. Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2: A clinic-based series. Cancer 2005;103:44–51. Narod SA, Brunet JS, Ghadirian P , et al. T amoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control stud y . Hereditary Breast Cancer Clinical Study Group. Lancet 2000;356:1876–1881. Gronwald J, T ung N, Foulkes WD, et al. T amoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer 2006; 1 18:2281–2284. Kau f f ND, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002;346:1609–1615. Rebbeck TR, Lunch H T , Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346:1616–1622. Piver MS, Jishi M F , T sukada Y , et al. Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cance r . A report of the Gilda Radner Familial Ovarian Cancer Registr y . Cancer 1993;71:2751–2755. Modan B, Hartge P , Hirsh- Y echezkel G, et al. Parit y , oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. N Engl J Med 2001;345:235–240. Narod SA, Risch H, Moslehi R, et al. Oral contraceptives and the risk of hereditary ovarian cance r . Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med 1998;339:424–428. Narod SA, Dubé M P , Klihn J, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 2002;94:1773–1779. Daly MB, Pilarski R, Axilbund JE,et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guideline s ® ). Genetic/Familial High-Risk Assessment: Breast and Ovarian V .1.2016. © 2016 National Comprehensive Cancer Network, Inc. Accessed February 18, 2016. Liede A, Karlan B Y , Narod SA. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: A review of the literature. J Clin Oncol 2004;22:735–742. DiCastro M, Frydman M, Friedman I, et al. Genetic counseling in hereditary breast/ovarian cancer in Israel: Psychosocial impact and retention of genetic information. Am J Med Genet 2002; 11 1:147– 151. Lodder LN, Frets PG, T risbu r g R W , et al. One year follow-up of women opting for presymptomatic testing for BRCA1 and BRCA2: Emotional impact of the test outcome and decisions on risk management (surveillance or prophylactic surgery). B r east Cancer Res T r eat 2002;73:97– 1 12. Crotser CB, Boehmke M. Survivorship considerations in adults with hereditary breast and ovarian cancer syndrome: State of the science. J Cancer Surviv 2009;3:21–42. Hamilton JG, Lobel M, Moyer A. Emotional distress following genetic testing for hereditary breast and ovarian cancer: A meta-analytic revie w . Health Psychol 2009;28:510–518. Reichelt JG, Møller P , Heimdal K, et al. Psychological and cancer-specific distress at 18 months post-testing in women with demonstrated BRCA1 mutations for hereditary breast/ovarian cance r . Fam Cancer 2008;7:245–254. Lodder L, Frets PG, T rijsbu r g R W , et al. Psychological impact of receiving a BRCA1/BRCA2 test result. Am J Med Genet 2001;98:15–24.

CONC L USION

nan nan

Pilarski R. Cowden syndrome: A critical review of the clinical literature. J Genet Couns 2009;18:13– 27. Conti S, Condò M, Posar A, et al. Phosphatase and tensin homolog (PTEN) gene mutations and autism: Literature review and a case report of a patient with Cowden syndrome, autistic disorder, and epileps y . J Child Neu r ol 2012;27:392–397. Smith JR, Ma r gusee E, W ebb S, et al. Thyroid nodules and cancer in children with PTEN hamartoma tumor syndrome. J Clin Endocrinol Metab 20 1 1;96:34–37. Zbuk KM, Eng C. Hamartomatous polyposis syndromes. Nat Clin Pract Gast r oente r ol Hepatol 2007;4:492–502. Kutscher AH, Zegarelli E V , Rankow RM, et al. Incidence of Peutz-Jeghers syndrome. Am J Dig Dis 1960;5:576–577. Beggs AD, Latchford AR, V asen H F , et al. Peutz-Jeghers syndrome: A systematic review and recommendations for management. Gut 2010;59:975–986. Lim W , Olschwang S, Keller JJ, et al. Relative frequency and morphology of cancers in STK 1 1 mutation carriers. Gast r oente r ology 2004;126:1788–1794. Hearle N, Schumacher V , Menko FH, et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 2006;12:3209–3215. Fitzgerald RC, Hardwick R, Hunstman D, et al. Hereditary di f fuse gastric cancer: Updated consensus guidelines for clinical management and directions for future research. J Med Gene t . 2010;47:436– 444. Kluijt I, Sijmons RH, Hoogerbrugge N, et al. Familial gastric cancer: Guidelines for diagnosis, treatment and periodic surveillance. Fam Cancer 2012; 1 1:363–369. Howlader N, Noone AM, Krapcho M, et al. (eds). SEER Cancer Statistics Revie w , 1975–2008, National Cancer Institute. Bethesda, MD. , based on November 2010 SEER data submission, posted to the SEER web site, 20 1 1. Accessed September 3, 2014. Kaurah P , MacMillan A, Boyd N, et al. Founder and recurrent CDH1 mutations in families with hereditary di f fuse gastric cance r . JAMA 2007;297:2360–2372. Brooks- W ilson AR, Kaurah P , Suriano G, et al. Germline E-cadherin mutations in hereditary di f fuse gastric cancer: Assessment of 42 new families and review of genetic screening criteria. J Med Genet 2004;41:508–517. Pharoah PD, Guilford P , Caldas C, et al. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gast r oente r ology 2001;121:1348–1353. Keller G, V ogelsang H, Becker I, et al. Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. Am J Pathol 1999;155:337–342. Oliveira C, Bordin MC, Grehan N, et al. Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred. Hum Mutat 2002;19:510–517. Frebou r g T , Oliveira C, Hochain P , et al. Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary di f fuse gastric cance r . J Med Genet 2006;43:138–142. Schrader KA, Masciari S, Boyd N, et al. Germline mutations in CDH1 are infrequent in women with early-onset or familial lobular breast cancers. J Med Genet 20 1 1;48:64–68. W alsh T , Casadei S, Lee MK, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. P r oc Natl Acad Sci U S A 20 1 1;108:18032–18037.

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nan nan

No te: page l oca t o r s f o ll owed b y f a nd t i nd icate fi gu re a nd ta b le , r es p ecti ve l y .

CONC L USION

A nan

A

CONC L USION

A nan

A20 prote i n, 4 Ab a r eli x, 309 A BC t r a nspo rt e r po l y m o r ph i s ms , 248 Ab i r ate rone ace t a t e, 19 1 t , 297 t , 299 t , 303 t , 310 A B L k i nase i nh i b it o r s, 255 Ab s orp ti on, 186 A C 220, 261 A ccele ra t ed pa rti a l- b r eas t irr ad iati on, 463 A c ro lei n, 209 A cti v e imm un i za ti on, 174 A c u te mye l ogenous l euke mi a (AML) F L T3 i nh i b it o r s i n, 260–261 is o cit ra t e dehyd r ogenase m u tati on s i n, 264 who l e geno m e ana l ys i s, 6–7 A c u te mye l o i d l euke mi a ( A ML) . S ee Ac u te m y el og e nou s le uk emia (A ML ) ADA M ( a d i s i n t eg ri n and m et all op r o tei n ase) famil y p r o tei n s , 4 ADA MTS s ( ADAMs w it h t hro m bo s pond i n do mai n s) , 4 Addu cts, DNA, 98 Ad e noma t ous po l ypos i s co li ( APC) workup a l go rit h m f o r , 378 f Ad e no sin e tri phospha t e b i nd i ng cassette (ABC) , 248 Ad j uv a n t t he r apy for breas t cance r , 162

CONC L USION

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B

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C

CONC L USION

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C A 125, 343 ov a r i an cance r and, 418, 430 u se i n r esponse eva l ua ti on, 343 Ca b azit axe l d e v el op m en t o f , 245

CONC L USION

C nan

s o mat ic a lt e r a ti on c l asses, 10– 1 1 s o mat ic a lt e r a ti ons pe r t u m o r , 5 ta xono m y o f t u m o r s, 16–19 Ca n ce r Geno m e A tl as, 14, 258 Ca n ce r ou t co m es r esea r ch, 133–134 Ca n ce r ri sk -r educ i ng agen t s a n ti - i n f ec ti ves, 400 a n ti - i n fl a mm a t o r y d r ugs, 394–395 a ro m a t ase i nh i b it o r s, 397 b i o c he mi ca l p r esc r een i ng a ssa y s , 385 b i o m a r ke r s as t a r ge t s o f , 387, 388 t b is ph o sphona t es, 399 cli n ic a l deve l op m en t o f , 386–388 d e f i n i ng o f , 384 d e v el op m en t a l phases o f , 387–388 d iet -d eri ved na t u r a l p r oduct s , 400 d i f l uo r o m e t hy l o r n it h i ne, 398, 39 9 t i d e n tifi ca ti on o f , 384 i n vit r o e f fi cacy m ode l s, 385–386 met for mi n, 399–400 mic ronu tri en t s, 388–394. S ee a ls o Micr onu trie n ts m u ltia gen t app r oaches t o, 400 pr ecli n i ca l deve l op m en t o f, 384–386 selecti ve es tr ogen r ecep t o r m odu lat o rs , 395–397, 39 6 t si gn al tr ansduc ti on m od ifi e rs , 398–400 stati n s , 398–399 5α- ster o i d r educ t ase i nh i b it o rs , 397–398 Ca n ce r s t e m ce ll s, 40–41 Ca n ce r su r ve ill ance sys t e m s, 138 Ca n ce r - a ssoc i a t ed fi b r ob l as t s, 35–36 Ca n ce r / ge rm-li ne an ti gens, 167–169 Ca n ce r /t es t es an ti gens, 167–169, 16 8 f Ca nfo s f ami de, 2 1 1

CONC L USION

C nan

C o l or ec ta l adeno m as, 1 14– 1 15 C o l or ec ta l cance r C EA ove r exp r ess i on, 169 d ieta ry f a t and, 1 12– 1 13 d ieta ry fi be r and, 1 14 fru it consu m p ti on and, 1 13 g e no m e l andscape, 1 2 f hor m one r ep l ace m en t t he r apy a nd, 139 i n ci dence o f t r e nds i n, 139–140 K RAS m u t a ti ons i n, 16 L yn c h synd r o m e and, 380– 3 81 meat i n t ake and, 1 15 ob esit y and, 125 phy sic a l ac ti v it y and, 124–125 PI K 3 CA m u t a ti ons i n, 3, 258 sc r ee n i ng f o r , 4 1 1 t , 415–416 c o l onoscop y , 415 c o m pu t ed t o m og r aphy co l ono sc op y , 415–416 f ecal occu lt b l ood t es ti ng, 415 f le x i b l e s i g m o i doscop y , 415 i n h i gh -ri sk pa ti en t s, 416 r ec o mm enda ti ons, 416, 41 6 t s yndro m es assoc i a t ed w it h , 38 0 t testi ng gu i de li nes, 38 0 t t r eated , so m a ti c m u t a ti ons i n, 1 8 f t r eatm en t o f b e vac i zu m ab, 334 cet ux im ab, 333 oxa li p l a ti n, 215 p a n it u m u m ab, 334 v e g eta b l e consu m p ti on and, 1 13 C o m b i ned m oda lit y t ox i c it y , 162

CONC L USION

C nan

C o mm un it y - based i n t e r ven ti on s , 13 1 f C o m p a nion d i agnos ti cs, 255, 342 C o m p a ra ti ve geno mi c hyb ri di zati on, 34, 60 C o m p le men t a r y and a lt e r na ti v e me d ici n e (CAM) drug int e r ac ti ons, 191 C o m p le men t a rit y de t e rmi n i ng re g i on s (CDRs) , 329 C o m p le men t- dependen t cy t o t ox icit y , 332 C o m p t on sca tt e ri ng, 153, 156 C o m pu t ed t o m og r aphy ( C T) c o l onoscop y , 415–416 p la nn i ng R T tr ea tm en t and, 155, 15 8 f C on c o m i t an t boos t , 162 C onf i d e nce i n t e r va l s, 133 C onf i d e n ti a lit y , gene ti c t es ti ng a nd, 431 C onfound i ng, 133 C on tact inh i b iti on, 26 C opy n um be r va ri a ti on, 49 C owd e n synd r o m e ca n cer ri sks assoc i a t ed w ith , 49 3 t c h a r act e ri s ti cs o f , 492–493 p at hogenes i s o f , 374 C pG isla nds, 268–269 CRC . See Co l o r ec t a l cance r C r iz o ti n i b, 25 6 t , 260, 296 t , 298 t CR LX1 0 1, 236 C ro ss - s ec ti ona l s t ud i es classifi ca ti on o f , 13 1 f d esc r ipti on o f , 130–131 Cry p t o t e t hya cryp t a, 228 β- C ryp t oxan t h i n, 388 ct DNA, 19 C TLA-4. See Cy t o t ox i c T l ympho c y te-ass o ciate d a n ti g e n 4 (CTLA- 4 ) C u m u la t i ve i nc i dence r a ti os, 131

CONC L USION

C nan

C ur c u m in, 401 t C urr e n t s m ok i ng, 353 C u ta n e ous T - ce ll l y m pho m a (CTCL) , 342 C y clic tetr apep ti des, 272 C y cl ophospha mi de ( Cy t oxan) acti v a t i on o f , 208, 20 8 f a dv e rse e f f ec t s ca rd i o t ox i c it y , 210 h em o rr hag i c cys titi s, 209 cli n ic a l pha rm aco l og y , 205 t d et ox ifi ca ti on o f , 20 8 f do ses and schedu l es, 20 6 t meta bo li s m o f , 20 8 f sta b il i t y o f , 207 s yn t h e s i s o f , 2 1 1 t h e r a peu ti c uses, 20 5 t t ox iciti es, 20 5 t C Y L D gene, 4 C YP3A , 305 C YP3A 4 do ceta xe l m e t abo li s m b y , 247 p aclit axe l m e t abo li s m b y , 246 C YP3A 5 , doce t axe l m e t abo lism b y , 247 C YP2 B 6, 208 C YP2 C 8, 246 C YP2D 6 gene i nh i b i t i on o f , 304–305 tam ox if en m e t abo li s m and, 472 C y ta r a b i ne ( a r a - C ) cata b oli s m o f , 228 cli n ic a l pha rm aco l og y , 228 d esc r ipti on, 228 do sa ges, 224 t

CONC L USION

D nan

D

CONC L USION

D nan

a dv e rse e f f ec t s, 247 t , 249 a pprova l o f , 245 ca p ecit ab i ne and, 227 cli n ic a l pha rm aco l og y , 247 do sa ges, 247 t drug int e r ac ti ons, 248 i d e n tifi ca ti on o f , 245 i nd ic a ti ons, 24 7 t mec h a n i s m s o f ac ti on, 245–246 r a d iati on sens iti v it y and, 152 Do se propo rti ona lit y , 187 Do se - cal cu l a ti on a l go rit h m s, 156–157 Doub le -s tr and b r eaks, 285. S ee a ls o DNA re p air Doxorub i c i n ( Ad ri a m yc i n ) al op eci a and, 210 c h a r act e ri s ti cs o f , 23 9 t d esc r ipti on o f , 238 i nd ic a ti ons f o r , 297 t li po s o m a l , 238 p e gy l a t ed, 281 p e gy l a t ed li poso m a l c h a rac t e ri s ti cs o f , 23 9 t t ox iciti es o f , 238 Dr i v e r m u t a ti ons, 47 “ Dr i v e r” m u t a ti ons, 13 D r o s op hil a me l anogas t e r , 2 Drug d e ve l op m en t , 339–349 Drug i n ter ac ti ons, 190–191 Drug m ay t ans i no i d - 1, 251 Drug r e s i s t ance a f te r a l ky l a ti ng agen t s, 2 1 1 ca n cer geno mi cs and, 19–20 Du ctal car c i no m a i n s it u ( DC IS)

CONC L USION

D nan

d esc r ipti on o f , 414 f eat ures o f , 453 t r eatm en t br e as t- conse r v i ng su r ge r y , 455 e ndoc ri ne t he r ap y , 455 e x c is i on w it h / w it hou t r ad iati on, 45 4 t Dyn ami c i ns t ab ilit y , mi c r o t ubu le , 245 Dy sm orpho l og y , sc r een i ng, 4 2 8

CONC L USION

E nan

Endo metri a l cance r h e r e d it a r y pro p hy l ac ti c su r ge r y , 372–373 ob esit y and, 125 PI K 3 CA m u t a ti ons i n, 3, 258 proph yl ac ti c su r ge r y i n, 37 3 –374 sc r ee n i ng f o r , 419 tam ox if en and, 302 Endo sta t i n, ang i ogenes i s i nh i b iti on b y , 318 Endo t h e l i a l ce ll s, 36 Endo t h e l i a l m onocy t e - ac ti va ti ng po l yp e p ti d e II , 90 Endox i f e n, 303–305 En e r g y , 11 1 En e r gy m e t abo li s m , 32 En e r gy r es tri c ti on, 1 1 1 En teca v i r , 83 En ti no stat , 27 1 t , 272, 273 Env i ron m en t a l exposu r es br east cance r ri sk and, 449 En zal u t a mi de, 29 7 t , 303 t , 310 Eph e dr a , 192 t Ep i d emi o l ogy met hods cas e - con tr o l s t ud i es, 132 – 133 c oho rt s t ud i es, 131–132 c ross - sec ti ona l s t ud i es, 1 30–131 ec olog i c s t ud i es, 130 i n t e r p r e t a ti on o f fi nd i ng s , 133 st u d y des i gn, 131 f t ypes o f s t ud i es, 130 m o le cu l a r , 97, 134–136 Ep i d e rma l g r ow t h f ac t o r r ecep t o r (EGFR) d esc r ipti on o f , 4 8 t

CONC L USION

E nan

r a d iati on syne r gy w it h, 164, 164 f sm oking and, 355 Ep i d e rmodysp l as i a ve rr uc if o r m is , 76 Ep i g e n eti c changes, 267–268, 26 8 f Ep i g e n eti c s il enc i ng, 16 Ep i g e n eti cs, 91–92 d esc r ipti on o f , 267 DNA m e t hy ltr ans f e r ase i nh i b it o rs , 273 Ep i podophy ll o t ox i ns, 241 Ep i rub i c i n d esc r ipti on o f , 239–240 Ep it h elial-t o -m esenchy m a l tra n siti on, 26, 30 EPO906. See E po t h il one B Epo t h ilo ne B, 251 Epo t h ilo ne D. See Deoxyepo t h il on e B Epo t h ilo nes, 251 Ep stei n-Ba rr v ir us (E BV ) B urk itt ’ s l y m pho m a and, 78 ca r cin o m as assoc i a t ed w it h, 79 c h a r act e ri s ti cs o f , 7 4 t h ist ory o f , 78 li f e c yc l e o f , 78 l y m pho i d cance r s, 79 pr e v e n ti on o f , 79 t r eatm en t o f , 79 ERBB2 gene c h a r act e ri s ti cs o f , 4 8 t , 90 Er i bu li n m esy l a t e, 29 9 t Er l o ti n i b ( T a r ceva ) cli n ic a l deve l op m en t o f , 257 food e f f ec t s on, 191 t i nd ic a ti ons, 25 6 t , 296 t for n o n - s m a ll ce ll l ung can ce r , 19

CONC L USION

F nan

Fa b do m a i ns, 329 Fa dro z o l e, 306 Fall op ia n t ube cance r , 372 Familial adeno m a t ous po l ypo sis ( F AP) d esm o i ds i n, 379 e x t r a co l on i c f ea t u r es o f , 379 proph yl ac ti c su r ge r y i n, 37 7 –380 workup a l go rit h m f o r , 378 f

CONC L USION

F nan

Familial b r eas t cance r/ ova ri a n ca n cer s ynd r o me , 36 9 t Familial cy li nd r o m a t os i s, 4 Famil y h i s t o r y ca n cer c l us t e ri ng, 428 g e n et ic counse li ng and, 427–428 Fa n c on i ane mi a ( F A ) f amil y h i s t o r y i n, 428 F A P . S e e F a mili a l adeno m a t ou s po l ypo sis Fat i n ta ke, 1 12– 1 13 Fati gu e r a d iati on -i nduced, 163 FcγRs , 3 31–332 Fecal o cc u lt b l ood t es ti ng, 415 Fee db ac k - con tr o ll ed dos i ng, 1 92–193 Fe nr eti n i de, 390–391 Fi b e r , d i e t a r y , 1 14– 1 15 Fi brob last g r ow t h f ac t o r r ecep t o r 1, 4 8 t Fi brob last g r ow t h f ac t o r s (FGFs) b asic , ang i ogenes i s and, 318 Fi brob last s, cance r - assoc i a t ed, 35–36 Fi r st -p a ss e f f ec t , 186 Fle x i b le s i g m o i doscop y , f o r co l o rectal ca n ce r , 415 F L T 3 g e ne, 48 t F L T3 i nh i b it o r s, 260–261 Fl ud a r a b i ne a dv e rse e f f ec t s, 225 t , 230 cli n ic a l pha rm aco l og y , 230 d esc r ipti on, 230 do sa ges, 225 t mec h a n i s m o f ac ti on, 230 mec h a n i s m o f r es i s t ance, 230 t h e r a peu ti c uses, 22 5 t Fl uor es cen t i n s it u hyb ri d i za t ion, 5 3 t , 57–58, 58 f

CONC L USION

F nan

F r a g me n t ana l ys i s, 5 3 t , 55, 56 f F r ee r a d i ca l s, 145 F ru its , 1 13– 1 14 F u l v est ran t do sa ge, 303 t ph a r m aco l og y , 306 st ru ct u r e o f , 306 f u se o f , 306

CONC L USION

G nan

G

CONC L USION

G nan

k i n ase i nh i b it o r s i n, 255 G e f iti n ib (Ir essa ) a pproved i nd i ca ti ons, 25 6 t cli n ic a l deve l op m en t o f , 257 food e f f ec t s on, 191 t for n o n - s m a ll ce ll l ung can ce r , 19 G emcita b i ne cli n ic a l pha rm aco l og y , 229 d esc r ipti on, 229 do sa ges, 224 t mec h a n i s m o f ac ti on, 229 mec h a n i s m o f r es i s t ance, 229 r a d iati on sens iti v it y and, 152 t h e r a peu ti c uses, 22 4 t t ox iciti es, 22 4 t , 229 G emt u zum ab ozoga mi c i n ( My l o ta r g ) c h a r act e ri s ti cs o f , 33 0 t d esc r ipti on o f , 251 u se o f , 332 G e n e am p lifi ca ti on, 47 G e n e e xp r ess i on p r o fili ng ov e r e xp r ess i on o f gene p r odu cts , 169 G e n e pr o duc t s, 169 G e n e sil enc i ng d esc r ipti on o f , 267–268 r e v e rsa l o f l aye r s, 270 G e n e - e nv ir on m en t i n t e r ac ti on s , 134 G e n es , pa t en t s on, 432 G e n etic counse li ng, 426–432 ca nd i da t es f o r , 426–427 c o m ponen t s o f , 427–430 c oun s e l o r s, 427 t DNA t es ti ng, 428–429

CONC L USION

G nan

fo ll ow - up a ft e r , 430 i nd ic a ti ons f o r , 427 t iss u es i n c on fi den ti a lit y , 431 d iscrimi na ti on, 431–432 i n sur ance, 431–432 p s y c hosoc i a l , 430–431 pr es y m p t o m a ti c t es ti ng and, 431 r e produc ti ve i ssues, 432 r is k as sess m en t and, 428 s urv e i ll ance op ti ons and, 4 2 9–430 G e n etic ep i de mi o l og y , 135 G e n etic I n f o rm a ti on Nond i sc rimi n ati on Act , 368 G e n etic po l y m o r ph i s m , 97 G e n etic suscep ti b ilit y , 97 G e n etic t es ti ng i n br e as t cance r , 489–497 cate g ori es o f r esu lt s, 429 d i r ect-t o - consu m e r , 432 p ate nts on genes, 432 G e no me ana l yses, 1 5 t , 20 G e no me i ns t ab ilit y and m u t a ti on, 33–34 G e no me- w i de assoc i a ti on s t u dies (G W AS) , 134–135 G e no me w i de gene exp r ess i o n p r o fili ng, 198–199 G e no mic mi c r oa rr ays, 5 4 t , 60–61 G e no mic s, 16, 92 G e no t ox i c ca r c i nogens, 95–96 G e no t ype - gu i ded che m o t he r ap y , 197 t G e no t yp i c m a r ke r s, 135 G e r m - lin e an ti gens, 167–169 G imatec an, 237 G i ng e r (Z i ng i ber o ffi c i na l e ) , 401 t G i nkgo, 192 t

CONC L USION

H nan

H allma rks, o f cance r a ng i ogenes i s i nduc ti on, 29–30 c h a r act e ri s ti cs t ha t f ac ilit a te , 33–35 e n e r gy m e t abo li s m , 32 e v a d i ng g r ow t h supp r esso rs , 26

CONC L USION

H nan

e v a d i ng imm une des tr uc ti on, 32–33 i nv asi on, 30–32 metast as i s, 30–32 ov e rv i ew o f , 24 pro li f er a ti ve s i gna li ng, 24–26 r e p lic a ti ve imm o rt a lit y , 28–29 r esisti ng ce ll dea t h, 26–29 t h e r a peu ti c t a r ge ti ng o f , 41–42, 42 f t u m o r - p r o m o ti ng i n fl a mm a ti on, 34–35 H alste d ia n t heo r y , 458 H a nd-foo t synd r o m e, 225 H a p Ma p, 2 H2AX c h ec kpo i n t pa t hways and, 145 stai n i ng o f , 146 f H aza rd ra ti os, 347 H ea d a nd neck cance r . See He a d a nd n ec k s qu am ou s cell carci no ma (HN SC C ) H ea d a nd neck squa m ous ce ll carci no ma (HNSCC) a d j uvan t t he r ap y , 162 cet uxi m ab f o r , 333 l o call y advanced, 161 t r eatm en t o f , 245 H ealt h i nsu r ance d isc r i m i na ti on i n, 431–432 g e n et ic t es ti ng and, 431–432 H ea r t r a d iati on t o l e r ance, 16 3 t H elical t o m o t he r ap y , 155, 155 f H elic obac t er py l or i st o mac h cance r and, 142 t r eatm en t o f , 400 H elic o s B i o S c i ences / He liS cop e , 5, 6 t , 7 f

CONC L USION

H nan

H emat o l og i c m a li gnanc i es. S ee a ls o s p ecific c an cers l y m phocy t e gene ti c m od ifi c ati on t o treat , 178–179, 17 9 t r it ux im ab f o r , 334–335 H emat opo i e ti c s t e m ce ll tr ansp la n tati on (HSCT) all ogene i c T - c e ll gene t he r apy i n, 181 H em orr h ag i c cys titi s, 209 H e p atitis B v ir us c h a r act e ri s ti cs o f , 7 4 t , 83 ma n a ge m en t o f , 83 H e p atitis C v ir us B - cel l non - Hodgk i n ’ s l y m pho ma a nd, 85 c h a r act e ri s ti cs o f , 7 4 t , 83–84 r eactiv a ti on o f , 84 H e p atitis v ir uses B . S e e Hepa titi s B v ir us C . S e e Hepa titi s C v ir us d esc r ipti on o f , 83 h e p at oce ll u l a r ca r c i no m a i ndu ce d b y , 84 mali gnanc i es assoc i a t ed w it h, 84–85 p at hogenes i s o f , 84 H e p at o c e ll u l a r ca r c i no m a ( H CC) . S ee a ls o Li v er ca n cer h e p at i ti s v ir uses and, 84 PI K 3 CA m u t a ti ons i n, 3 t r eatm en t o f s ora f en i b, 322 H e r e d it a r y b r eas t and ova ri an ca n cer s ynd r o me , 489 H e r e d it a r y cance r synd r o m es g e n et ic counse li ng i n, 42 7 t list of, 369 t s u r g er y ’ s r o l e i n p r even ti on o f , 368–381 H e r e d it a r y d i f f use gas tri c canc er (HDGC) , 36 9 t , 370 f , 494 H e r e d it y , m o l ecu l a r ep i de mi o l ogy a nd, 135

CONC L USION

H nan

Hyp e rba ri c oxygen ( HBO ) t h era p y , 151 Hyp e r eo s i noph ili c synd r o m e ( HES) d esc r ipti on o f , 257 F IP1L1 -P DG F Rα tr ans l oc ati on, 257 Hyp e rfr a c ti ona ti on, 162 Hypofr acti ona t ed who l e - b r eas t irra d iati on, 463 Hypofr acti ona ti on, 162 Hypox i a ac u te , 151 c hron i c, 151 d i f fu si on -m ed i a t ed, 151 oxygen consu m p ti on and, 151 progn o s ti c va l ue o f , 151 t r a n si en t , 151 Hypox i a -i nduc i b l e f ac t o r ( H IF) , 261, 317–318 Hy ste r e c t o m y , 373, 430

CONC L USION

I nan

I

CONC L USION

I nan

t ox iciti es, 20 5 t IKK-α, 9 1 I ll u mi n a H iS eq 2000, 6 t I ma g e -gu i ded r ad i a ti on t he r apy (IG R T) s y stem s used i n, 155–156 I mati n i b m esy l a t e ( G l eevec, Gli v ec) a pproved i nd i ca ti ons, 25 6 t for c hron i c m ye l ogenous le uk emia , 20, 255 food e f f ec t s on, 191 t for h y pe r eos i noph ili c syndro me , 257 I mm on i u m i ons, 20 4 f I mm un e i n fl a mm a t o r y ce ll s, 36–37 I mm unocon j uga t es, 332 I mm unocy t ok i ne con j uga t es, 3 32 I mm unog l obu li n r ecep t o r s, 331–332 I mm unog l obu li ns (I gGs ) d esc r ipti on o f , 329 fun cti ona l do m a i ns o f , 329 st ru ct u r e o f , 329 I mm unosupp r ess i on fro m a l ky l a ti ng agen t s, 210 I mm uno t he r ap y , 167–181 acti v e imm un i za ti on app r o ac h es , 174 a dop ti ve ce ll tr ans f e r , 174–176, 175 f a n ti - c y t o t ox i c T -l y m phocy te a n ti g e n 4 b l o c k i ng a n ti bod ies , 172–173 a n ti gens i n v ir a l- assoc i a t ed ca n cers , 170 a pproaches t o, 17 0 t ca n cer/ ge rm-li ne an ti gens, 167–169 c h ec kpo i n t i nh i b it o r s, 172–173 c h im e ri c an ti gen r ecep t o r s a n ti- CD19, 179–181 d es c ri p ti on o f , 179 h em a t o l og i c an ti gens t a r g ete d b y , 181

CONC L USION

I nan

g e n e p r oduc t s, 169 i n te r l euk i n - 2, 171 mela nocy t e d i f f e r en ti a ti on a n ti g e n s , 169 t u m or an ti gens, 167–170 I mm uno t ox i ns, 332 In ci d e nce, tr ends i n, 138–143, 14 0 t In ci d e nce dens it y r a ti os, 131 Ind els , 10 Ind i r ect a ng i ogenes i s i nh i b it o r , 320 Ind i v i dua l- based t he r ap y , 131 f Inf lam ma ti on i n a ng i ogenes i s, 90–91 i n ca nce r d i agnos i s, 92 d esc r ipti on o f , 88 e p i g e ne ti cs and, 91–92 g e no mi cs and, 92 i n i nvas i on, 90 i n met as t as i s, 91 m o le cu l a r bas i s o f , 88 or i g i n s o f , 89 f i n pro lif e r a ti on, 90 i n s urv i va l , 89 ta r g et ed t he r ap i es and, 92 t r a n sc r i p ti on f ac t o r s, 89 i n t r a ns f o rm a ti on, 88–89 word o ri g i n o f , 88 Inf lam ma t o r y b r eas t cance r (IBC) , 477–478 Inf lam ma t o r y ce ll s, 31 Infor ma t i on b i as, 133 Infor me d consen t , 409 In te gr i n s β-4, 3 2 0 d esc r ipti on o f , 320

CONC L USION

I nan

In te n sit y -m odu l a t ed r ad i a ti on t h era py (IM R T) b eam i n t ens it y pa tt e r ns, 15 5 is odo s e d i s tri bu ti on, 15 9 f t r eatm en t p l ann i ng, 158 In te r acti on, 133 In te rf e ron - α b e v aci zu m ab w it h, 321 In te r le u ki n ( s ) IL-2, 171 d es c ri p ti on o f , 171 imm une s tim u l a ti on w it h, 167 for m e t as t a ti c m e l ano m a, 171–172 for m e t as t a ti c r ena l ce ll c a n ce r , 171 sa fe ad mi n i s tr a ti on o f , 1 7 2 t ox i c iti es, 172 IL-6 r a d i a ti on t ox i c it y and, 1 6 3 IL-7, 48 t In te rn atio na l Cance r Geno m e C on s o rti u m (ICGC) , 14–15, 258 In te rn atio na l W o r k i ng G r oup (IWG) , 342 In te r stitial pneu m on iti s, 209 In t r ae p ith e li a l neop l as i as, 38 8 t In t r a o c u l a r m e l ano m a. See Uv eal mela no mas Ion izi ng r ad i a ti on (I R ) . See a ls o Ra d iati on t h era py br east cance r ri sk and, 449 ca n cer ri sks assoc i a t ed w ith , 104–105 cell cy c l e e f f ec t s, 151 cell dea t h caused b y , 104 cell s u r v i va l and, 149–150 cell u l a r r esponses o f , 103– 1 05 d ama ge i nduc ti on m echan isms , 102–103, 10 3 f d e f i n iti on o f , 102 DNA da m age caused b y , 102–103, 146 f

CONC L USION

J nan

J

CONC L USION

J nan

J A K 1, 48 t J A K 2, 48 t J A K 3, 48 t

CONC L USION

K nan

K

CONC L USION

K nan

K i n ases , cance r s d ri ven b y , 258 K i n esi n s p i nd l e p r o t e i n ( K S P , EG 5 ) , 252 KIT c h a r act e ri s ti cs o f , 4 8 t K li n e f elt e r synd r o m e, 477 K RAS d esc r ipti on o f , 4 8 t m u tati ons BR A F m u t a ti ons and, 13 i n co l o r ec t a l cance r , 16, 1 8 f i n panc r ea ti c cance r , 16 Ku h ete rod im e r , 147–148

CONC L USION

L nan

st ru ct u r e o f , 307 f L e upro l ide do sa ge, 303 t , 308 po te ncy o f , 308 rou te o f ad mi n i s tr a ti on, 308 L e v eti r a ce t a m , 210 L e w is Y an ti gen, 181 L i f e/ A P G S O Li D3, 5 L i f e/ A P G S O Li D 5500x l , 6 t , 7 f L i f est y le br east cance r ri sk and, 449 L i - F r a u m en i synd r o m e br east cance r ri sk and, 36 9 t d esc r ipti on o f , 491–492 d ia gnos ti c c rit e ri a f o r , 492 t g e n es li nked t o, 36 9 t h ist ory o f , 491 p at hogenes i s o f , 374 p s y c hosoc i a l i ssues o f , 492 t u m ors assoc i a t ed w it h, 49 1 t , 491–492 L i n ea r a cce l e r a t o r x -r ay beam p r odu cti on, 15 5 f L i n ea r e ne r gy tr ans f e r (LET) , 102, 146 f L i n ea r - q uad r a ti c m ode l , 104 L i n itis p l as ti ca, 370. See a l so Di f f u se g astric ca n cer (DGC) L i po s o m a l doxo r ub i c i n ( Dauno X o me) , 238. S ee a ls o D oxo r ub ici n L i qu i d bi ops i es, 19 L i v e r ca nce r . See a l so Hepa t o cell u lar carci no ma (HCC) r a d iati on t o l e r ance, 16 3 t sc r ee n i ng f o r , 417 L i v e r d i sease, r ad i a ti on -i nduced, 163 l n cR NA, 9 Lobu la r ca r c i no m a i n s it u (LCIS) , 368, 450, 452–453 Lo call y- a dvanced b r eas t canc er (LABC) , 477–478

CONC L USION

L nan

Lor aze pa m for b u su lf an -i nduced se i zu res , 210 Lo ss of f unc ti on m u t a ti ons, 50 Lo ss of he t e r ozygos it y ana l ys is , 59 Lou is - B a r synd r o m e, 36 9 t Low li n e a r ene r gy tr ans f e r , 145 Low-dose co m pu t e ri zed t o m og ra ph y , f o r l ung ca n cer scree n i ng, 419–42 0 Lung al ky l a ti ng agen t t ox i c it y , 210 mic ronu tri en t e f fi cacy i n, 389–390 r a d iati on t o l e r ance, 16 3 t Lung ca nce r . See a l so Non - s mall cell l ung ca n cer a d j uvan t t he r ap y , 162 as b es tos and, 108 EG FR m u t a ti ons i n, 256–257 fru it consu m p ti on and, 1 14 i n ci dence o f , 138–139 l o call y advanced, 161 l ow-dose co m pu t e ri zed t omog ra phy scree n i ng f o r , 419–420 ob esit y and, 127 phy sic a l ac ti v it y and, 127 sc r ee n i ng f o r , 4 1 1 t , 419–420 s qu am ous ca r c i no m a, 16 v e g eta b l e consu m p ti on and, 1 14 Lu tei n izi ng ho rm one r e l eas i ng ho rm on e (LHRH) d esc r ipti on o f , 30 3 t L y m phocy t es a dop ti ve ce ll t he r apy f o r , 176–178 r a d iati on k illi ng o f , 163 L y m pho m as. See a l so Hodgkin ’ s l y m pho ma; N on -H odgk i n ’ s l y m pho ma ; s p ecific l ymphoma IWG c rit e ri a f o r , 342 pr imar y e f f us i on, 80

CONC L USION

L nan

L y m phop r o lif e r a ti ve d i so r de r s K a pos i ’ s sa r co m a and, 80 L yn c h s ynd r o m e proph yl ac ti c su r ge r y i n, 37 3 –374, 380–381 s urv e i ll ance p r ocedu r es, 430 t o tal abdo mi na l co l ec t o m y i n, 38 1 t

CONC L USION

M nan

M

CONC L USION

M nan

Mac rop h ages c y t o t ox i c it y o f , 331 t u m o r - assoc i a t ed, 91 MAGE- 1 , 167 M AGE-A1 an ti gen, 16 8 f M AGE-A3 an ti gen, 168, 16 8 f M AGE-A12 an ti gen, 168 Ma gn eti c r esonance im ag i ng ( MRI) r a d iati on t he r apy p l ann i ng u si ng, 157, 15 8 f sc r ee n i ng gu i de li nes, 45 0 t Maj or his t oco m pa ti b ilit y co m p le x (MHC) m o lec u les , 167, 16 8 f Mali gn a n t m e l ano m a, 7. See a ls o Mela no ma(s) Mammali an t a r ge t o f r apa m yc i n (m T OR) acti v a t i on o f , 25 i nh i b i to r s o f , 261 for b r eas t cance r , 263 d es c ri p ti on o f , 323 i nd i ca ti ons f o r use o f , 263 for t ube r ous sc l e r os i s, 263 Mammali an t a r ge t o f r apa m yc i n -ass o ciate d p r o tei n c o m p le x es (mTORC) p at hwa y , 262 f MammaPri n t , 469 Mamm og r aph y , 140, 410, 412, 414 Ma n tle ce ll l y m pho m a ( MC L) bor te zo mi b f o r , 281

CONC L USION

M nan

h e r e d it a r y , 431 M EN - 2 and, 374–377 RE T m u t a ti ons i n, 37 5 t s por a d i c, 375 t v a nd e tan i b f o r , 322 Me du ll ob l as t o m a PI K 3 CA m u t a ti ons i n, 3 Me g est ro l ace t a t e do sa ge, 3 1 1 for h ot fl ashes, 302 ph a r m aco l og y , 3 1 1–312 rou te o f ad mi n i s tr a ti on, 30 3 t t ox iciti es, 3 1 1 Mela n-A, 169 Mela nocy t e d i f f e r en ti a ti on ant i g e n s (MDAs) , 169 Mela nocy t es, 169 Mela no m a ( s ) BRA F m u t an t , 16, 258–26 0 g e n e mu t a ti ons i n, 4 i n ci dence o f , 142 metast a ti c d i sease c o m p l e t e r esponse t o tr e atme n t , 17 2 f i n t e rl euk i n - 2 t he r apy f o r , 171–172 T cell s r eac ti ve t o, 167 u lt r a vio l e t li gh t and, 106 uv eal BA P 1 m u t a ti on i n, 4 d es c ri p ti on o f , 4 Mel ph al an ( A l ke r an ) a d mi n i s tr a ti on o f , 207 c h a r act e ri s ti cs o f , 207 cli n ic a l pha rm aco l og y , 205 t do ses and schedu l es, 20 7 t

CONC L USION

M nan

M y el opro lif e r a ti ve d i so r de r s, 258 M y el o s upp r ess i on cla dr i b i ne and, 230 cl of a rab i ne and, 231 g emc i t ab i ne and, 229 M YH- as soc i a t ed po l ypos i s (MAP) , 377–380 M yof i brob l as t s, 35

CONC L USION

N nan

N

CONC L USION

O nan

O

CONC L USION

O nan

Ob esit y br east cance r and, 123–124, 140 ca n cer ri sk and, 123 c o l orec t a l cance r and, 125 d esc r ipti on o f , 1 1 1, 123 e ndo m e tri a l cance r and, 125 es ophagea l adenoca r c i no m a a nd, 126 k i dn e y cance r and, 126 l ung cance r and, 127

CONC L USION

P nan

P

CONC L USION

P nan

P 58.2, 169

CONC L USION

P nan

K RAS m u t a ti ons, 16 ob esit y and, 126 sc r ee n i ng f o r , 417 si gn al ing pa t hways, 1 2 f Pa n it u m u m ab ( V ec ti b i x ) b i nd i ng o f , 332 c h a r act e ri s ti cs o f , 33 0 t mec h a n i s m o f ac ti on, 334 Pa nob i nos t a t (L BH589 ) , 272–273 Pa p a n icol aou (P ap ) s m ea r s ce rv i ca l cance r sc r een i ng u si ng, 417 c y t o l og i c t e rmi no l ogy f o r , 417 d esc r ipti on o f , 417 Pap ill omav i r i dae, 75 Pa p ill o m av ir uses, 75–76 Pa rox eti ne (P ax il) for h ot fl ashes, 302 Passe ng er m u t a ti ons, 13, 47 Patc h e d - 1, 264 Pate n ts , o n genes, 432 Pat up il one. See E po t h il one B Paz op a n i b ( V o tri en t) d esc r ipti on o f , 322 do sa ges, 319 t i nd ic a ti ons, 25 6 t , 298 t , 319 t VEG F R i nh i b iti on b y , 261 P 53 BP 1 p r o t e i n, 145 P D-1, 173 P D325901, 259 PDGFR A , 48 t PDGFR B , 48 t P DX1010. See Be li nos t a t (PDX 1010 ) Pe d iat r ic pa ti en t s. See a l so C hil d re n

CONC L USION

P nan

pr es y m p t o m a ti c t es ti ng i n, 4 31 s o li d t u m o r s i n, 5 Pemet r e xed ( A limt a ) cli n ic a l pha rm aco l og y , 223 d esc r ipti on o f , 223 do sa ges, 224 t t h e r a peu ti c uses, 22 4 t t ox iciti es, 22 4 t h a nd -f oo t synd r o m e, 22 5 m ucos iti s, 225 m ye l osupp r ess i on, 225 r as hes, 225 Pe r ic y te s, 29, 36 Pe r i ph e ra l neu r opa t hy d esc r ipti on o f , 293 Pe r it on e a l se r ous ca r c i no m a, 373 Pe r t u z u m ab, 29 8 t , 330 t , 333, 481 Pe r t u z u m ab i n j ec ti on, 29 6 t Pe u tz - Je ghe r s synd r o m e br east cance r ri sk i n, 36 9 t g e n et ics o f , 36 9 t i n ci dence o f , 494 PF -023 4 1066 ( c ri zo ti n i b ) , 260 P h a r ma codyna mi cs d esc r ipti on o f , 186, 188, 18 8 t do se adap t a ti on us i ng, 192–193 v a r ia b ilit y i n, 187–192 P h a r ma cogeno mi cs of c he m o t he r apy d r ug t ox icit y , 199–201 t h e r a py gu i ded b y , 196 t u m or r esponse, 196–199 P h a r ma cok i ne ti cs a b s orp ti on, 186

CONC L USION

P nan

P hy ll odes t u m o r , 477 P hy sical ac ti v it y br east cance r and, 123–124 ca n cer ri sk and, 123 c o l orec t a l cance r and, 124–125 d e f i n iti on o f , 123 e ndo m e tri a l cance r and, 125 es ophagea l adenoca r c i no m a a nd, 126 l ung cance r and, 127 ov a r i an cance r and, 127 pro st a t e cance r and, 126–127 r e n al ce ll ca r c i no m a and, 126 PI K 3 C A m u t a ti ons i n c o l o r ec t a l cance r , 1 8 f d esc r ipti on o f , 4 8 t , 198 i n e ndo m e tri a l cance r , 258 s o mat ic, 3 t u m ors exp r ess i ng, 258 PI K 3R1, 48 t , 263 PI K 3R2, 48 t P15I NK 4b gene, 274 Place n tal g r ow t h f ac t o r , ang i og e n esis a nd, 317 Platelet -de ri ved g r ow t h f ac t o r (PDGF) a ng i ogenes i s and, 317 d esc r ipti on o f , 36 P DG F- α, 257 Platelet -de ri ved g r ow t h f ac t o r rece p t o rs (PDGFRs) , 258 Plati nu m agen t s a n al ogues o f , 214–221 c h em is tr y o f , 214 r a d iati on sens iti v it y and, 152 P L C O Cance r S c r een i ng T ri al, 421 P LX4032, 19

CONC L USION

P nan

P ro li f e ra ti ve s i gna li ng, 24–26 P ro m y el ocy ti c l euke mi a (P M L) , 335 P ro sta g l and i ns, 394 P ro state cance r cast r ati on -r es i s t an t s urv i va l r a t es i n, 17 4 f d iet a nd, 1 13 i n ci dence o f , 141–142 m or talit y r a t es, 141–142 ob esit y and, 127 phy sic a l ac ti v it y and, 126–127 sc r ee n i ng f o r , 420–422 T MP R SS2 -ER G tr ans l oca ti on s , 10 t r eatm en t o f ca b a z it axe l f o r , 249 m o rt a lit y r a t es and, 421 r a d i o t he r ap y , 161 P ro state g l and mic ronu tri en t s e f fi cacy i n, 392 P ro state- spec ifi c an ti gen sc r ee n i ng p r og r a m s, 420–4 2 2 se r ial l eve l s o f , 343 P ro teasom e i nh i b it o r s b i o m a r ke r s f o r , 281 c h em ica l c l asses o f , 279 i n c he m o t he r ap y , 279–282 s yn t h eti c a n tit u m o r ac ti v it y , 280 pr e c li n i ca l pha rm aco l ogy o f , 279–280 P ro teasom es, 28 0 t P ro tei n a se K, 51 Ps y c ho s oc i a l i ssues g e n et ic counse li ng and, 430–431

CONC L USION

Q nan

Q

CONC L USION

Q nan

Qu alit y o f lif e ( QO L) r es ponse eva l ua ti on us i ng, 3 48 Qu iza r ti n i b, 261

CONC L USION

R nan

t o le r a nce doses, 16 3 t t ox icit y o f , 162 t u m or oxygena ti on and, 151 t yp es o f , 160–161 Ra d iati o n onco l ogy b i o l og i c aspec t s o f , 145–150 pr i n ci p l es o f , 145–164 t r eatm en t i n t en t , 161–162 t r eatm en t p l ann i ng, 157–158 Ra d iati o n r eca ll , 238 Ra d iati o n t he r apy a n tican ce r agen t s w it h, 164 for breas t cance r , 459–460 cli n ic a l app li ca ti ons o f , 160–161 fr actio na t ed, 150–152, 162 late e f f ec t s o f , 163 for pros t a t e cance r , 161 se n siti za ti on t o, 151 Ra d iati o n-i nduced pneu m on itis d esc r ipti on o f , 163 Ra d ical scavenge r s, 102 Ra d i o acti ve i so t opes, 159 Ra d i ofrequency r ad i a ti on, 10 6 –107 Ra d i o i m m unocon j uga t es, 333 Ra d i u m , 29 6 t Ra don, 104 Ra d3-r el a t ed ce ll cyc l e checkpo i n ts , 105–106 Ral ox i fene for breas t cance r , 141 c h em op r even ti ve use o f , 4 5 0–453 d esc r ipti on o f , 396 do sa ge, 303 t e f f ica cy o f , 305

CONC L USION

R nan

ph a r m aco l og y , 305–306 proph yl ac ti c use o f , 453 Ram u ci ru m ab, 324 Ra ndo m ized c li n i ca l tri a l s, 1 1 1, 409, 41 3 t Ra p al ogs, 261, 263 Ra p am yc i n, 261. See a l so Sir o lim u s RAS g e ne d esc r ipti on o f , 25 R AS /MAP k i nase, 263 R AS- R A F- M E K -E RK pa t hw a y , 259 f Rate r ati os, 131 RB pro t e i n, 26 Reacti ve oxygen spec i es, 107 Real - tim e po l y m e r ase cha i n r e acti on, 52–54, 5 3 t Reass or tm en t , a ft e r r ad i a ti on, 150–151 Rec A, 148 Rece n t s m ok i ng, 353 R E C I ST 1.0 gu i de li nes, 339–341, 34 1 f Rect u m mic ronu tri en t s e f fi cacy i n, 392 r a d iati on t o l e r ance, 16 3 f Re d me a t , 1 15 Re gor a fen i b, 29 7 t , 319 t , 323 Reim burse m en t , 431–432 Rejecti on r esponses, 167 Re n al c e ll ca r c i no m a ( RCC ) . S ee a ls o Ki dn e y ca n cer c DNA sc r een i ng, 169 e v e ro lim us f o r , 323 metast a ti c c o m p l e t e r esponse t o tr e atme n t , 17 2 f i n t e rl euk i n - 2 t he r apy f o r , 171 phy sic a l ac ti v it y and, 126 s or a fen i b f o r , 322

CONC L USION

R nan

Re oxyg e na ti on, 151 Re p licati ve senescence, 28 Re p lic o n s, i n iti a ti on f a il u r e, 1 45 Re popu lati on accel e r a t ed, 162 a f te r r ad i a ti on, 150 Res pon se E va l ua ti on C rit e ri a i n S o li d T u m o rs (RECIST) , 339 e v al u ati on c rit e ri a, 34 0 t –341 t WHO c rit e ri a co m pa r ed w i th, 34 1 f Res v e r a t r o l , 40 1 t RE T m u tati ons o f d es c ri p ti on o f , 4 9 t g e no t ype - pheno t ype co rrelati on s , 375 i n m edu ll a r y t hy r o i d ca rci no ma , 37 5 t i n M E N, 376 f r is k -r educ i ng t hy r o i dec t o m y i n, 375–376, 37 7 f st u di es o f , 260 R ET t yros i ne k i nase r ecep t o rs , 260 Reti n a , tam ox if en t ox i c it y o f , 302 Reti no i d X r ecep t o r - se l ec ti ve reti no i d s , 390 Reti no i ds as ca nce r ri sk -r educ i ng agen ts , 388–392, 39 0 t Ret ro s p e c ti ve s t ud i es, 131 Ret rov i ruses a n im a l , 81–82 c hron i c tr ans f o rmi ng, 81 classifi ca ti on o f , 81 e ndogenous, 81 e xog e nous, 81 Re v e r se tr ansc ri p t ase po l y m e rase c h ai n reacti on, 5 3 t , 54–55, 55 f Re v limi d. See L ena li do mi de R h a bdomyosa r co m a

CONC L USION

R nan

i n ci dence o f , 491 Ris k r ati os, 131 Ris k-r ed uc i ng b il a t e r a l sa l p i ngo - oopho rect o m y (RRSO) c o m p li ca ti ons o f , 373 ov a r i an cance r and, 372–373 st ud ies o f , 372 Ris k-r ed uc i ng t hy r o i dec t o m y , 375–376, 377 f Rit ux im ab ( R it uxan ) c h a r act e ri s ti cs o f , 33 0 t C HOP r eg im en w it h, 334 fun cti on o f , 332 for h e ma t o l og i c m a li gnanc ies , 334–335 r es ponse r a t es, 2 1 1 R NA- se quenc i ng, 59–60 R o c h e , 5, 6 t , 7 f R og letimi de, 306 R o mi d e ps i n c h a r act e ri s ti cs o f , 27 1 t d esc r ipti on o f , 272 HDAC i nh i b iti on b y , 273 ROS1, 49 t R uxo liti n i b, 25 6 t , 298 t

CONC L USION

S nan

S

CONC L USION

S nan

S -1, 227 S ph ase a rr est o f , 145 c h ec kpo i n t pa t hways and, 145–147 S - a d e nosy lm e t h i on i ne, 1 16 Sali no s po r a mi de A, 279, 28 0 t Sal p i ngo - oopho r ec t o m y proph yl ac ti c, 368–381 r is k-reduc i ng b il a t e r a l , 372 – 373

CONC L USION

S nan

for o v a ri an cance r , 412 t , 418–419 for p a nc r ea ti c cance r , 417 Pa p a n i co l aou (P ap ) s m ea r ce rv i ca l cance r sc r een i ng u si ng, 417 c y t o l og i c t e rmi no l ogy f o r , 417 d es c ri p ti on o f , 417 for pros t a t e cance r , 420–422 for s k i n cance r , 412 t , 422 t r e nds i n, 138, 139 t Sc r ee n i ng t es t s asses s m en t o f , 407–409 i nfor m ed consen t f o r , 409 le ng t h b i as, 408, 40 9 f n e g at ive p r ed i c ti ve va l ue, 407 ou tc o m es o f , 409 ov e rd i agnos i s, 408 p e rfor m ance cha r ac t e ri s ti c s o f , 407, 40 8 t po siti ve p r ed i c ti ve va l ue, 407, 40 7 t r a ndo mi zed tri a l s, 409 r es u lts o f , 407–409 Sec ond ar y p rim a r y cance r s a f te r a l ky l a ti ng agen t s, 209 i on izi ng r ad i a ti on as cause o f , 104 pr e v e n ti on o f , 389–390 sm oking e f f ec t s on, 355 t opo i so m e r ase i nh i b it o r s as ca u se o f , 241 Sec ond-gene r a ti on sequenc i n g , 6–9 Seiz ur es , a l ky l a ti ng agen t i nd uce d, 210 Selecti on b i ases, i n ep i de mi o l og ic st ud ies , 133 Selecti ve es tr ogen r ecep t o r m odu lat o r (SERM) ca n cer tr ea tm en t w it h, 30 3 t t r eatm en t us i ng, 302–306 Selecti ve es tr ogen r ecep t o r m odu lat o rs , 395–397, 39 6 t

CONC L USION

S nan

sc r ee n i ng f o r , 41 2 t , 422 Small c ha i n f a tt y ac i ds, 272 Small i n t es ti ne r a d iati on t o l e r ance, 16 3 t SMO ( sm oo t hened ) gene, 4 8 t Sm ok el ess t obacco, 66 Sm ok i ng. See a l so T obacco ca n cer r ecu rr ence and, 354 ca n cer tr ea tm en t t ox i c it y and, 354–355 e p i d e r m a l g r ow t h f ac t o r r e ce p t o r a nd, 355 g l ob al r a t es o f , 64 hu ma n pap ill o m a v ir us and, 355 m or talit y a f f ec t ed b y , 353–354 N ati ona l Onco l ogy Assoc iati on stateme n ts on, 356 sec ond p rim a r y cance r ri sk s , 355 Sm ok i ng cessa ti on al gor it h m f o r , 357 f assista nce w it h, 358 fu t ur e cons i de r a ti ons f o r , 362–363 im p lem en t a ti on o f , 356–358 i n te rv e n ti ons f o r , 360–361 m od el tr ea tm en t p r og r a m s f o r , 361–362, 362 t n ic o ti ne r ep l ace m en t t he r apy f o r , 359, 36 0 t ph a r m aco l og i c tr ea tm en t f o r , 359–360, 360 t r es ou r ces f o r , 358 t st r ategi es f o r , 359 t s uppor t du ri ng, 361 Sm o l d e ring adu lt T - ce ll l eukem ia-l y m pho ma , 82 Smoo t hened gene, 4 8 t S N2 al ky l a ti on r eac ti ons, 203 S NDX-275. See E n ti nos t a t S od i u m pheny l bu t y r a t e, 272 S ofo s buv i r , 84

CONC L USION

S nan

S o matic ana l ys i s, 199 S o mat os t a ti n ana l ogs ca n cer tr ea tm en t w it h, 30 3 t S or a f e n ib ( Nexava r) a dv e rse e f f ec t s o f , 322 for B RA F m u t an t m e l ano ma , 258–260 cli n ic a l u tilit y , 321–322 do sa ges, 319 t food e f f ec t s on, 191 t i nd ic a ti ons, 25 6 t , 296 t , 319 t o f f- ta r ge t ac ti v iti es o f , 261 for t hy r o i d cance r , 260 So r ang iu m ce ll u l osum, 251 S oy pro d uc t s, 1 16– 1 17 S p atial add iti v it y , 164 S p ecim ens, 51, 134 S p i n al c o r d r a d iati on t o l e r ance, 16 3 t S p lit dose r epa ir (S DR ) , 150–151 S qu am ous ce ll ca r c i no m as (SCCs) h ea d a nd neck. See Head and n ec k s qu am ou s cell carci no ma l ung, 16 u lt r a vio l e t li gh t and, 106 St . J ohn ’ s wo rt ( Hyper i cum pe rf o r a t u m) , 192 t Sta b le d i sease (S D ) , 344 S T A T 1, 48 t S T A T 3, 48 t Stat h mi n ove r exp r ess i on, 252 Stem ce l l( s ) , 37–38, 40–41 Stem ce l l tr ansp l an t a ti on (S C T) all ogene i c T - c e ll gene t he r apy w it h , 181 Ste ro i d recep t o r RNA ac ti va to r , 9

CONC L USION

S nan

S urv i vorsh i p br east cance r , 474–475, 475 t S yndrome o f i napp r op ri a t e se creti on o f a n ti d i u retic ho rm on e (SIADH) v i n ca a l ka l o i ds and, 251 S yn t h eti c l e t ha lit y , 286, 288 S yn t h eti c phase. See S phase

CONC L USION

T nan

T

CONC L USION

T nan

TE R T - CLPT M1 L , 135 T eseta xe l , 248 T estic u lar cance r cis p lati n f o r , 214 Th ali do mi de (T ha l o mi d ) a n tia ng i ogen i c p r ope rti es o f , 318, 320 i n ca nce r t he r ap y , 318 d esc r ipti on o f , 293–294, 29 5 t le n ali do mi de and, 294, 335 6-Th i oguan i ne ( 6 -T G ) d esc r ipti on, 229 do sa ges, 225 t t h e r a peu ti c uses, 22 5 t t ox iciti es, 22 5 t Th i opur i ne m e t hy ltr ans f e r ase, 47, 199–200 6-Th i opu ri ne m e t hy ltr ans f e r a se (TPMT) , 230 6-Th i opu ri nes cli n ic a l pha rm aco l og y , 230 d esc r ipti on, 229–230 mec h a n i s m o f ac ti on, 229 mec h a n i s m o f r es i s t ance, 229–230 t ox iciti es, 230 Th i o te pa, 204 cli n ic a l pha rm aco l og y , 205 t do ses and schedu l es, 20 7 t t h e r a peu ti c uses, 20 5 t t ox iciti es, 20 5 t Thro m bocy t open i a cl of a rab i ne and, 231 Thro m bospond i n - 1 (TSP- 1 ) a ng i ogenes i s i nh i b iti on b y , 318, 320 d esc r ipti on o f , 29 Thy mi d yl a t e syn t hase (TS) , 223

CONC L USION

T nan

TN F -α r a d i a ti on t ox i c it y and, 1 6 3 T u m or oxygena ti on, 151 T u m or p r og r ess i on, 3 f T u m or s upp r esso r genes m u tati ons, 2 T u m or ig enes i s r esea rch tim e li ne, 4 f T u m o r - infiltr a ti ng l y m phocy tes c u lt ur e o f , 169 T u m o r - pr o m o ti ng i n fl a mm a ti on, 34–35 T u mstat in, 318 T yro si ne k i nase i nh i b it o r s d esc r ipti on o f , 321–322 T yro si ne - k i nase do m a i n, 3

CONC L USION

U nan

U

CONC L USION

U nan

Ub i qu iti n - p r o t easo m e pa t hwa y , 279 UGT1A1, 235 U lt r a v i o l e t li gh t ca n cer ri sks assoc i a t ed w ith , 106 cell dea t h caused b y , 106 cell m e m b r ane r ecep t o r ac t iv ati on, 106 cell u l a r r esponses t o, 105, 10 5 f d ama ge i nduc ti on m echan isms o f , 105 d esc r ipti on o f , 102 non m e l ano m a sk i n cance r a nd, 106 pho t o imm unosupp r ess i on, 1 06 Ra d3- r e l a t ed ce ll cyc l e checkpo i n ts , 105–106 t r a n sl es i on DNA syn t hes i s, 105 Ur i n a ry bl adde r t ox icit y o f a l ky l a ti ng agen ts , 209 Uro t h eli a l cance r s

CONC L USION

U nan

hu ma n ca r c i nogens and, 98–99 U te r i n e cance r s d esc r ipti on o f , 430 U te r i n e sa r co m as a f te r tam ox if en t he r ap y , 302 Uv eal me l ano m as d esc r ipti on o f , 4

CONC L USION

V nan

V

CONC L USION

V nan

V(D) J re j o i n i ng, 148 V e g eta bles, 1 13– 1 14 V e g eta r ia n d i e t , 1 17 V em ur af en i b, 256 t , 299 t V e n la f axi ne (E f f exo r) for h ot fl ashes, 302 V i nb last ine ( VB L) do sa ges, 247 t i nd ic a ti ons, 24 7 t mec h a n i s m o f ac ti on, 250 t ox iciti es, 24 7 t , 251 V i n ca alk a l o i ds cli n ic a l pha rm aco l og y , 249 drug int e r ac ti ons, 250 mec h a n i s m o f ac ti on, 249 ov e rv i e w , 249 r a d iati on sens iti v it y and, 153 t ox icit y , 250–251 V i n c r isti ne ( VCR ) al op eci a and, 210 do sa ges, 247 t i nd ic a ti ons, 24 7 t , 297 t mec h a n i s m o f ac ti on, 249–250 r a d iati on sens iti v it y and, 153 t ox icit y , 247 t , 250–251 V i nf l un i ne, 250 V i nor el b i ne ( VR L) do sa ges, 247 t mec h a n i s m o f ac ti on, 250 t ox iciti es, 24 7 t , 250–251 V i r al - as soc i a t ed cance r s, 170 V i r al - m ed i a t ed gene de li ve r y , 176 V i r t u al co l onoscop y , 415–416

CONC L USION

W nan

W a rbu r g e f f ec t , 32 W a rf a r in , 305 W ate rf all p l o t s, 34 8 f , 348–349 Who le -exo m e ana l ys i s, 9–10 Who le -geno m e ana l ys i s, 6–9 W or l d H ea lt h O r gan i za ti on (WHO) e v al u ati on c rit e ri a, 34 0 t –341 t R E C I ST c rit e ri a co m pa r ed wit h, 34 1 f t r eatm en t r esponse c rit e ri a, 339

CONC L USION

X nan

X

CONC L USION

Y nan

Y tt r i u m mi c r osphe r es, 161

CONC L USION

Z nan

Z