Carcinogenesis

**Carcinogenesis,** wanda kuma ake kira **oncogenesis** ko **tumorigenesis,** shine samuwar ciwon daji, inda kwayoyin halitta suka canza zuwa kwayoyin cutar kansa . Tsarin yana halin canje-canje a salon salula, kwayoyin halitta, da matakan epigenetic da rarraba kwayoyin halitta mara kyau. Rarraba tantanin halitta tsari ne na ilimin lissafi wanda ke faruwa a kusan dukkanin kyallen takarda kuma a ƙarƙashin yanayi iri-iri. Yawanci, ma'auni tsakanin yaduwa da tsarin mutuwar kwayar halitta, a cikin nau'i na apoptosis, ana kiyaye shi don tabbatar da kuma amincin kyallen takarda da gabobin . Bisa ga ka'idar da aka yarda da ita ta carcinogenesis, ka'idar maye gurbi na somatic, maye gurbi a cikin DNA da epimutations wanda ke haifar da ciwon daji ya rushe waɗannan matakai masu tsari ta hanyar tsoma baki tare da shirye-shiryen da ke tsara tsarin tafiyar matakai, tada ma'auni na yau da kullum tsakanin yaduwa da mutuwar kwayar halitta. Wannan yana haifar da rarrabuwar tantanin halitta mara sarrafawa da haɓakar waɗannan sel ta zaɓin yanayi a cikin jiki. Wasu maye gurbi ne kawai ke haifar da ciwon daji yayin da yawancin maye gurbi ba sa.

Bambance-bambancen kwayoyin halittar da aka gada na iya sa mutane su kamu da cutar kansa. Bugu da ƙari, abubuwan muhalli kamar su carcinogens da radiation suna haifar da maye gurbi wanda zai iya taimakawa wajen bunkasa ciwon daji. A ƙarshe kuskuren bazuwar a cikin kwafin DNA na yau da kullun na iya haifar da ciwon daji da ke haifar da maye gurbi.  Ana buƙatar jerin maye gurbi da yawa zuwa wasu nau'ikan kwayoyin halitta kafin tantanin halitta ta al'ada ya canza zuwa kwayar cutar kansa . A matsakaita, alal misali, 15 "maye gurbin direba" da "fasinja" 60 ana samun su a cikin ciwon daji na hanji. Maye gurbi a cikin kwayoyin halittar da ke daidaita rabon tantanin halitta, apoptosis (mutuwar tantanin halitta), da gyaran DNA na iya haifar da yaduwar kwayar halitta da ciwon daji.

Ciwon daji ya kasan ce shi ne asalin cuta na ƙayyadaddun ci gaban nama. Domin tantanin halitta ta al'ada ya canza zuwa kwayar cutar daji, dole ne a canza kwayoyin halittar da ke daidaita girma da bambance-bambancen kwayar halitta. Canje-canje na kwayoyin halitta da na epigenetic na iya faruwa a matakai da yawa, daga riba ko asarar dukkanin chromosomes, zuwa maye gurbin da ya shafi DNA nucleotide guda ɗaya, ko don yin shiru ko kunna microRNA wanda ke sarrafa bayanin kwayoyin 100 zuwa 500. Akwai manyan nau'ikan kwayoyin halitta guda biyu waɗanda waɗannan canje-canjen suka shafa. Oncogenes na iya zama kwayoyin halitta na yau da kullun waɗanda aka bayyana a manyan matakan da ba su dace ba, ko kuma canjin kwayoyin halitta waɗanda ke da sabbin abubuwa. A kowane hali, bayyanar da waɗannan kwayoyin halitta suna haɓaka mummunan yanayin ƙwayoyin cutar kansa. Kwayoyin da ke hana Tumor su ne kwayoyin halitta waɗanda ke hana rarraba tantanin halitta, rayuwa, ko wasu kaddarorin ƙwayoyin cutar kansa. Kwayoyin da ke hana Tumor sau da yawa suna naƙasa ta hanyar haɓaka canje-canjen kwayoyin halitta masu cutar kansa. A ƙarshe Oncovirinae, ƙwayoyin cuta waɗanda ke ɗauke da oncogene, an rarraba su azaman oncogenic saboda suna haifar da haɓakar kyallen ƙwayar cuta a cikin gidan . Ana kuma kiran wannan tsari azaman canji na hoto ko bidiyo mai zagaya yanar gizo da sauri.

## Dalilai

### Genetic da epigenetic
Akwai nau'ikan rarrabuwa iri-iri don sauye-sauyen iri-iri na kwayoyin halitta waɗanda zasu iya ba da gudummawa ga haɓakar ƙwayoyin cutar kansa . ya kasan ce kuma yawancin waɗannan canje-canjen maye gurbi ne, ko canje-canje a cikin jerin nucleotide na DNA na genomic. Hakanan akwai canje-canje na epigenetic da yawa waɗanda ke canza ko an bayyana kwayoyin halitta ko ba a bayyana su ba. Aneuploidy, kasancewar adadin ƙananan ƙwayoyin chromosomes, shine canji na kwayoyin halitta wanda ba maye gurbi ba, kuma yana iya haɗawa da riba ko asarar ɗaya ko fiye da chromosomes ta hanyar kurakurai a cikin mitosis . Manyan maye gurbi sun ƙunshi ko dai shafewa ko kwafin wani yanki na chromosome. Ƙwararrun kwayoyin halitta yana faruwa ne lokacin da tantanin halitta ya sami kwafi da yawa (sau da yawa 20 ko fiye) na ƙaramin yanki na chromosomal, yawanci yana ɗauke da ɗaya ko fiye da oncogenes da kayan gado na kusa. Juyawa yana faruwa lokacin da yankuna biyu na chromosomal daban-daban suka zama masu haɗaka da juna, sau da yawa a wani yanayi na musamman. Wani sanannen misali na wannan shine chromosome Philadelphia, ko fassarar chromosomes 9 da 22, wanda ke faruwa a cikin ciwon sankarar jini na myelogenous na kullum, kuma yana haifar da samar da furotin BCR - abl fusion, wani oncogenic tyrosine kinase . Ƙananan maye gurbi sun haɗa da maye gurbi, gogewa, da shigarwa, wanda zai iya faruwa a cikin mai inganta kwayar halitta kuma ya shafi maganganunsa, ko kuma zai iya faruwa a cikin tsarin codeing na kwayar halitta kuma ya canza aiki ko kwanciyar hankali na samfurin furotin . Rushewar kwayar halitta guda ɗaya kuma na iya haifar da haɗuwa da kayan halitta daga kwayar cutar DNA ko retrovirus, kuma irin wannan lamarin na iya haifar da bayyanar cututtuka na ƙwayoyin cuta a cikin tantanin halitta da ya shafa da zuriyarsa.

### Lalacewar DNA

Ana ɗaukar lalacewar DNA a matsayin tushen farko na cutar kansa. Fiye da 60,000 sababbin abubuwan da ke faruwa ta dabi'a na lalacewar DNA sun tashi, a matsakaici, kowane tantanin halitta, kowace rana, saboda tsarin tsarin salula na zamani (duba labarin lalacewar DNA (wanda ke faruwa a zahiri) ).

Ƙarin lalacewa na DNA na iya tasowa daga fallasa ga wasu abubuwan waje. A matsayin misali ɗaya na wakili na ƙwayar cuta na waje, hayaƙin taba yana haifar da ƙarin lalacewar DNA, kuma wannan lalacewar DNA na iya haifar da haɓakar cutar kansar huhu saboda shan taba. A cikin wasu misalan, hasken UV daga hasken rana yana haifar da lalacewar DNA wanda ke da mahimmanci a cikin melanoma, *Helicobacter pylori* kamuwa da cuta yana samar da nau'in oxygen mai yawa wanda ke lalata DNA kuma yana taimakawa ga ciwon daji na ciki,  da kuma *Aspergillus flavus* metabolite aflatoxin ne. wani wakili mai lalata DNA wanda ke haifar da ciwon hanta.

Hakanan ana iya haifar da lalacewar DNA ta abubuwan da aka samar a cikin jiki . Macrophages da neutrophils a cikin epithelium mai kumburi mai kumburi sune tushen nau'in oxygen mai amsawa wanda ke haifar da lalacewar DNA wanda ke haifar da tumorigenesis na colonic, da bile acid, a cikin manyan matakan da ke cikin mazaunin mutane suna cin abinci mai yawa, kuma suna haifar da lalacewar DNA. da kuma taimakawa ga ciwon daji na hanji. 

Irin waɗannan ɓangarorin ɓarna da ɓarna na lalacewa na DNA ana nuna su a cikin kwalayen da ke saman adadi a wannan sashe. Matsayin tsakiya na lalacewar DNA a ci gaba zuwa ciwon daji ana nuna shi a mataki na biyu na adadi. Abubuwan tsakiya na lalacewar DNA, sauye-sauye na epigenetic da ƙarancin gyaran DNA a ci gaba zuwa ciwon daji ana nunawa a cikin ja.

Rashin gyare-gyaren DNA zai haifar da ƙarin lalacewar DNA don tarawa, kuma yana ƙara haɗarin ciwon daji. Misali, mutanen da ke da nakasa da aka gada a cikin kowane nau'in halittar DNA guda 34 (duba labarin DNA gyara-rashi cuta ) suna cikin haɗarin cutar kansa, tare da wasu lahani suna haifar da damar kusan 100% na ciwon daji (misali p53 maye gurbi).  Ana nuna irin waɗannan maye gurbi na ƙwayoyin cuta a cikin akwati a gefen hagu na adadi, tare da nunin gudunmawar su ga ƙarancin gyara DNA. Duk da haka, irin wannan maye gurbi (wanda ke haifar da ciwon daji mai saurin shiga jiki) sune sanadin kusan *kashi ɗaya cikin ɗari* na cutar kansa. 

Yawancin ciwon daji ana kiran su marasa gado ko "ciwon daji". Kusan kashi 30 cikin 100 na cututtukan daji na lokaci-lokaci suna da wasu abubuwan gado waɗanda a halin yanzu ba a bayyana su ba, yayin da yawancin, ko kashi 70% na cututtukan daji na lokaci-lokaci, ba su da wani ɓangaren gado.

A cikin ciwon daji na lokaci-lokaci, rashi a gyaran DNA yana faruwa lokaci-lokaci saboda maye gurbi a cikin kwayar gyaran DNA; da yawa akai-akai, raguwa ko rashin bayyanar kwayoyin halittar DNA shine saboda sauye-sauyen epigenetic wanda ke rage ko yin shiru . Ana nuna wannan a cikin adadi a mataki na 3 daga sama. Alal misali, don ciwon daji na launi na 113 da aka yi nazari a cikin jerin, hudu kawai suna da maye gurbi a cikin DNA na gyaran MGMT, yayin da mafi yawan sun rage MGMT magana saboda methylation na yankin mai gabatarwa na MGMT (canjin epigenetic).

Lokacin da aka rage bayyanar kwayoyin halittar DNA, wannan yana haifar da ƙarancin gyaran DNA. Ana nuna wannan a cikin adadi a matakin na 4 daga sama. Tare da ƙarancin gyaran DNA, lalacewar DNA ta ci gaba a cikin sel a mafi girma fiye da matakin al'ada (matakin 5 daga sama a cikin adadi); wannan barnar da ta wuce gona da iri tana haifar da karuwar mitar maye gurbi da/ko epimutation (matakin 6 daga saman adadi). Gwaji, ƙimar maye gurbi yana ƙaruwa sosai a cikin sel marasa lahani a cikin gyara rashin daidaituwa na DNA ko a cikin gyaran haɗin gwiwa na Homologous (HRR). Sabuntawar chromosomal da aneuploidy suma suna ƙaruwa a cikin ƙwayoyin da ba su da lahani na HRR  Yayin gyaran ɓangarorin DNA guda biyu, ko gyara wasu lalacewar DNA, wuraren da ba su cika cikakke ba na iya haifar da tsit na epigenetic.

Maye gurbin somatic da sauye-sauyen epigenetic da ke haifar da lalacewa ta DNA da rashi a cikin gyaran DNA sun taru a cikin lahani . Lalacewar filaye sune kyawu masu bayyana al'ada tare da sauye-sauye da yawa (an tattauna a cikin sashin da ke ƙasa), kuma su ne madogarar gama gari don haɓaka ɓarna da haɓakar ƙwayoyin nama a cikin ciwon daji. Irin wannan lahani na filin (mataki na biyu daga kasan adadi) na iya samun sauye-sauye da yawa da kuma sauye-sauye na epigenetic.

Ba shi yiwuwa a tantance dalilin farko na mafi yawan takamaiman cututtukan daji. A kuma wasu ƴan lokuta, dalili ɗaya kawai ya wanzu: alal misali, ƙwayar cuta HHV-8 tana haifar da duk sarcomas na Kaposi . Koyaya, tare da taimakon dabarun cututtukan cututtukan daji da bayanai, yana yiwuwa a samar da ƙididdigewa mai yuwuwar sanadi a cikin ƙarin yanayi. Misali,kuma ciwon huhu na huhu yana da dalilai da yawa, ciki har da shan taba da kuma radon gas . Maza masu shan taba a halin yanzu suna kamuwa da cutar kansar huhu a cikin adadin mazan da ba su taba shan taba ba sau 14: damar cutar kansar huhu a cikin mai shan taba na yanzu da shan taba ke haifar da shi kusan kashi 93% ne; akwai yuwuwar kashi 7% cewa cutar kansar huhu ta mai shan taba ta samo asali ne ta hanyar radon gas ko wani abin da ba na shan taba ba.  Waɗannan alaƙar ƙididdiga sun ba da damar masu bincike su fahimci cewa wasu abubuwa ko ɗabi'a na cutar kansa. Hayakin taba yana haifar da karuwar lalacewar DNA na waje, kuma wannan lalacewar DNA shine yuwuwar cutar kansar huhu saboda shan taba. Daga cikin fiye da 5,000 mahadi a cikin taba hayaki, da genotoxic DNA-damaging jamiái da ke faruwa duka biyu a mafi girma yawa, da kuma wanda ke da karfi mutagenic effects ne acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide da isoprerence . . 

Yin amfani da dabarun nazarin kwayoyin halitta, yana yiwuwa a siffata rikiɗewar, ƙayyadaddun ƙayyadaddun ƙwayoyin cuta ko ɓarna na chromosomal a cikin ƙari, kuma ana samun ci gaba cikin sauri a fagen hasashen hasashen wasu masu cutar kansar bisa ga nau'in maye gurbi. Misali, kusan rabin duk ciwace-ciwacen ciwace-ciwace suna da lahani na p53. Wannan maye gurbi yana da alaƙa da rashin hasashe, tun da waɗancan ƙwayoyin ƙwayar cuta ba su da yuwuwar shiga cikin apoptosis ko tsarin mutuwar tantanin halitta lokacin lalacewa ta hanyar jiyya. Maye gurbi na Telomerase yana cire ƙarin shinge, yana ƙara adadin lokutan da tantanin halitta zai iya raba. Sauran maye gurbi suna ba da damar ƙwayar cuta ta haɓaka sabbin hanyoyin jini don samar da ƙarin abubuwan gina jiki, ko kuma don daidaitawa, yaduwa zuwa wasu sassan jiki. Duk da haka, da zarar an kafa ciwon daji yana ci gaba da samuwa kuma yana samar da ƙananan clones. An ba da rahoto a cikin 2012 cewa samfurin ciwon daji na koda guda ɗaya, wanda aka yi samfurin a wurare daban-daban guda tara, yana da maye gurbi na "ko'ina" 40, wanda aka samu a duk yankuna tara, maye gurbi 59 da wasu suka raba, amma ba duka wurare tara ba, da kuma 29 "masu zaman kansu" kawai. samuwa a wani yanki. 

Layukan sel waɗanda duk waɗannan sauye-sauyen DNA suka taru suna da wahala a gano su, amma layukan shaidu biyu na baya-bayan nan sun nuna cewa ƙwayoyin sel na yau da kullun na iya zama sel na asali a cikin cututtukan daji. Na farko, akwai ingantacciyar alaƙa mai inganci (Spearman's rho = 0.81; P