Ukusinda kwi-Hereditary Cancer Breast
Abantu abaninzi banenkxalabo "ngemfuza" okanye umdlavuza webele. Siyazi ukuba utshintsho lwe-BRCA lunokunyusa kakhulu umngcipheko wokuba nomdlavuza webele. Kodwa kulabo abafumana umdlavuza webele , njani ukusinda kuqhathaniswa nalabo abahlakulela umdlavuza webele kodwa abanalo ukuguquka kwemfuza? Sinezifundo eziliqela eziye zajonga lo mbuzo.
Ngokuqinisekileyo, kuthusa ukuba ufunde enye yolu tshintsho. Ukuba uthetha ukuguqulwa kwe-BRCA kunokuthetha ukuvavanya kwamanye amanyathelo, ukwenza izigqibo ezinyanzelisa intliziyo, kunye nokunyanga okunyanga xa umhlaza kufuneka uhlakulele. Kodwa uphando olutsha malunga nokuphila kwangexesha elide kunye nokutshintshwa kwezinto ezinokuthi litshintshe lunokunciphisa ezinye zezoyiko.
Kufuneka, nangona kunjalo, ukujonga ezi zifundo ngokubanzi. Ezinye izifundo zijonge kuphela abafazi abaselula. Abanye baye bajonga ixesha elihlukeneyo xa bevavanya ukusinda. Kwaye abanye baye bavavanya ukuba yintoni unyango olunokuthi luphuculise ukusinda kakhulu kunabesifazana abaneenguquko ze-BRCA.
Masiqale ngokuhlaziya iinguqulelo ze-BRCA, kutheni zibalulekile ekuphuhliseni umdlavuza webele, kwaye ukuba le ngqanda ingahluke njani kwii-cancer zebele ezingenalo ifa, uze uthethe ngezinto esizifundileyo kwindlela yokuphila.
I-BRCA iinguqulelo-Inkcazo kunye neMisebenzi yeGenesis ye-BRCA
Siyazi ukuba umdlavuza udla emva kokuba uchungechunge lwe-DNA gene gene changes.
Izahlulo zethu zifana neprogram ezithwala iiplani ezenziwe emzimbeni wethu. Imiyalelo ethwalwe kwiijethi ithwala izikhokelo zokwenza amaprotheni avela kwii-enzymes eziphula ukutya kwethu, kwiiprotheni ezisebenzela ukusikhulula kumhlaza.
Ukuguquguquka kwegama kuthetha naluphi na uhlobo lomonakalo kwi-DNA eguqula ukubunjwa kwayo.
I-DNA yethu yenziwe ngama-chromosomes angama-46, 23 ukusuka koomama kunye no-23 ovela koobawo. I-Genethi, kwakhona, iinqununu zama-chromosomes ezithwala izikhokelo zokuvelisa amaprotheni athile. Ezi zikhokelo zenziwe njengomtya weetekisi (iibini zisezantsi) ezisebenza njengekhowudi.
Ukuba iileta (iziseko) kwi-gene zixutyaniswa, izikhokelo zingaba zichanekileyo kwaye ngoko kube yiplani yeprotheni engavumelekanga. Ngamanye amaxesha iziseko zongezwa (izongezo), ngamanye amaxesha zisusiwe (ukususa utshintsho) kwaye ngamanye amaxesha zilungiswa kwakhona. (Kukho nezinye iinguqu ezinokuthi zenzeke kwakhona). Kwenzeka ntoni emva kokuba utshintsho luzuze ilifa okanye luzuzwe ngexesha lomdala, kuxhomekeke kwimisebenzi yemfuza ethile.
Iigciwane ze-BRCA zixinzelelo zezilwanyana zengqumbo . Zibalela iiproteni ezikhusela ukukhula kweemvamisa ezifana nomhlaza wesifuba kunye nomhlaza we-ovari. Ngokukodwa, i-BRCA ikhowudi yeeprotheni ezinoxanduva lokulungisa umonakalo kwi-DNA kwiiseli zethu (zilungisa izikhefu kwi-DNA ephindwe kabini).
Ngamanye iiseli zethu ziqulethe iigleji ezimbini ze-BRCA, ikopi enye kumama kunye nekopi enye evela kubaba. Iigleji ze-BRCA ziyi-autosomal ngokweqile, oku kuthetha ukuba zombini iikopi ze-gene kufuneka zitshintshwe ukuze umhlaza unxulumene nokuguqulwa kwemfuza ukuphuhlisa.
Ekubeni uninzi lwabantu luzuza igalelo elilodwa lomsundu (oku kubhaliwe njenge-BRCA1 / 2), ukuba utshintsho lwe-BRCA lwandisa umngcipheko wakho wesifo somhlaza ( unomdla wokuba nomhlaza) kodwa akuthethi ukuba uya kuba nomhlaza. Ukuze umhlaza uqalise enye ikopi yemfuza kuyakufuneka iguqulwe. Ukuguqulwa kwesi sibini ngokuqhelekileyo kufumaneka (ukusuka kumonakalo we-DNA ngenxa yokusingqongileyo, ukhetho lwezinto zokuphila, okanye ukutshintsha kwezinto eziqhelekileyo zeeseli).
Oku kunokudideka kakhulu xa sithetha ngala mahluko ahlukeneyo omtshintsho, nangona ichaza ukuba kutheni wonke umntu onokuguquguquka kwe-BRCA uya kuba nomhlaza.
Utshintsho olubini olukhokelela kumhlaza wesisu kwininzi yabasetyhini abakwi-BRCA + kwaye bahlakulele umdlavuza webele, kubandakanya ukuguquka komgca-gciwane kunye nokuguqulwa kwamanzi.
- I-Germ-line okanye iinguqu ezenziwa njengefa (oku kuquka ukuguqulwa kwe-BRCA njengoko kuchaziwe apha) kudluliselwa kumama okanye uyise kumntwana ekukhulelwe.
- IsiSomatic okanye ukuguqulwa kwamanzi (ukutshintshwa okwenzeka ngenxa yesiphumo se-DNA ehambelana nendalo, izinto zokuphila, okanye iinkqubo eziqhelekileyo zokusetyenziswa kwamanzi kwiiseli) zenzeka nanini na ngexesha lobomi bomntu.
(Kukho neengxaki zegciwane ezihlobene nomhlaza ezibizwa ngokuba yi-oncogenes ezizuze njengefa kwi-autosomal fashion fence ukuze iikopi enye ye-gene iguqulwe iyadingeka ukuqhuba ukukhula komhlaza, kodwa oku kungaphezulu kweli nqaku).
Ukuqonda ukuguqulwa kwe-BRCA
Xa uthetha ngomngcipheko weenguquko ze-BRCA, kubalulekile ukubonisa ukuba asikhulumi ngenguqu ekhethekileyo kwiDNA. Kunoko kunamakhulu eendlela ezahlukeneyo kwii-gene ze-BRCA ezinokuguqulwa. Njengoko kuphawuliwe ngasentla, ezi zinezifo zinezixhobo ezingaphezulu (incwadi), isiseko esingekhoyo, okanye iziseko zingaphinde zilungiswe ngandlela-thile.
Kukho ukungafani komngcipheko womhlaza phakathi kwe-BRCA1 kunye ne-BRCA2 utshintsho, kunye nolunye uhlobo oluthile lokuguqulwa kwezinto ezikhoyo kwi-gene. Umngcipheko jikelele wesifo somhlaza kubantwana abasetyhini ngaphandle kwe-BRCA ukuguqulwa kwe-BRCA ku-12 ekhulwini. Kulabo abane-BRCA1 ukuguqulwa komngcipheko, umngcipheko oqhelekileyo unama-55 ukuya kuma-65 ekhulwini (kwaye unokuphakama njengama-87 ekhulwini). Kwabo abane-BRCA2 ukuguqulwa komzimba, malunga neepesenti ezingama-45 zamabhinqa baya kuvelisa umdlavuza webele xa uneminyaka engama-70.
Umdlavuza we-ovariya uvela kuma-1.3 ekhulwini kwabasetyhini ngokubanzi. Kwabo abane-BRCA1 zinguqu, i-39 ekhulwini kulindeleke ukuba ikhulise umdlavuza we-ovari, ngelixa i-11 ukuya kuma-17 ekhulwini kulabo abane-BRCA2 ukuguqulwa kwesifo kuya kuhlakulela isifo.
Kukho ezinye iidrari ezinokudityaniswa neentshukumo ze-BRCA, njengomdlavuza wesibeletho, umdlavuza we-pancreatic, kunye nomdlavuza wamaphaphu .
Ukwahlukana kwiCanscers Breast kwiAbasetyhini abane-BRCA
Kukho ukungafani kwimihlaza yesisu phakathi kwabasetyhini abaneenguquko ze-BRCA kunye nabangenawo utshintsho. Oku kubalulekile ukuba ezinye zezo ngqu
Iinguqu ze-BRCA zixhaphake kakhulu kubasetyhini abasebancinci abahlakulela umdlavuza webele. Kwabo abangaphantsi kweminyaka engama-40, kucingelwa ukuba ngaphezulu kwe-10 ekhulwini yeekansini zidibene ne-BRCA. Ngokwahlukileyo, inani liza kufutshane nama-5 ekhulwini kwabasetyhini abadala abanesifo.
Amagciwane okubeleka kwabasetyhini abaneengxaki ze-BRCA zithatha ukuba neekomhlaza ezinebanga eliphezulu. Ibanga lokuxhamla liyingcamango yokugubha kwe-tumor.
Amanomdla okubeletha esiswini kubasetyhini abaneenguquko ze-BRCA (ingakumbi i-BRCA1 zatshintshi) azinako ukufumana i-estrogen receptor okanye i-progesterone receptor. Akunamathuba amaninzi ukuba abe yi- H2 positive . I-hormone receptors , kunye ne-HER2, ziyamkela kwi-cell cancer zesifuba apho i-estrogen okanye izinto zokukhula ezibophelela ukuqhuba umkhondo womhlaza.
Ngamanye amagama, " i- cancer" yesifo seengxube ezithandwayo zixhaphake kakhulu kubasetyhini abane-BRCA. Ngokuqhelekileyo, iintsholongwane zengxube zengxube zengxaki ezinzima kunzima ukunyanga, kuba akukho unyango lwe-hormonal okanye ii-AG ezijoliswe kuzo ziya kusebenza.
Kwinqanaba elincomekayo, iintsholongwane zentliziyo kubasetyhini abane-BRCA zinguqulelo zivame ukuphendula kangcono kwi-neoadjuvant chemotherapy (i-chemotherapy ezinikezwe ngaphambi kokuhlinzwa) kunezo ezingenalo utshintsho.
I-BRCA iinguqulelo kunye ne-Non-BRCA ye-Breast Breast Cancer (BRCAX)
Kudla ngokudideka ukuthetha ngeenguquko ze-BRCA kunye nomhlaza wesibeleko . I-BRCA inguquko yimbangela yesifo somhlaza wesibeleko kodwa asiyiyo yonke i-cancer yebele eyenziwa yi-BRCA. Ngokubanzi, iinguqu ze-BRCA zingu-20 kuya kuma-25 ekhulwini lweengcingo zebele zesifo kunye ne-5 ukuya kwi-10 ekhulwini ze-cancer zebele.
Iingcambu ze-Hereditary ezingahambelani neenguquko ze-BRCA zibhekiswa njenge-BRCA yomhlaza wesibeleko okanye intsapho ye-BRCAX. Ukuguqulwa kwe-Gene edibene nomhlaza wesisu kubandakanya abo kwi-ATM CDH1, CHEK2, PALB2, PTKN, STK11, kunye ne-TP53. Kukho uninzi oluninzi olulindele ukufumanisa, kodwa uphando lusezinyathelo zokuqala.
Ukusinda Ngaphandle Kokungaguquki kwe-BRCA (Isifundo se-2018)
Xa uthetha ngokusinda nge-BRCA utshintsho kubalulekile ukuqaphela ukuba sithetha ngamanani. Sineenkcukacha malunga nendlela "umyinge" umntu onokuthi "umyinge" we-BRCA unokuguquka kunye nesiphumo sakhe. Kodwa ekubeni kukho ukuhlukahluka okuthe ngqo kulolu tshintsho, kwaye abantu bakhetha iindlela ezahlukeneyo zokulawula umhlaza wabo, amanani awabalulekanga ukuba iziphumo zabantu ngabanye. Abantu azinako izibalo.
Ucwaningo lwango-2018 olupapashwe kwiLancet Oncology luye lwaba lukhulu ukuhlolisisa umdlavuza wentsholongwane kulabo abane-BRCA utshintsho olunxulumene nalabo abanomdlavuza webele. ngokusinda ngomhlaza wesisu ohambelana neenguquko ze-BRCA.
Iqela labasetyhini abaneminyaka engama-40 nangaphantsi lalandelwa iminyaka eyi-10, kunye nokuqhubekeka kokuvavanywa kwinye, ezintlanu kunye neminyaka eyi-10 emva kokuxilongwa. Emva kweminyaka engama-10, ixabiso lokusindisa labo babengenayo i-BRCA kwaye i-BRCA engalunganga yayifanayo. Enyanisweni, kwiminyaka embalwa yokuqala, abo abaneengxaki zokuguquka kwe-BRCA kunye nomhlaza wesibeleko esinezintathu zineziphumo ezingcono kunezo zinezifo ezithintekayo. Abo babenokuguqulwa kwe-BRCA bekunokwenzeka ukuba babe ne-double mastectomy, kodwa kwakungabikho mmahluko phakathi kwabo babenomastectomy okanye i-lumpectomy eneemitha.
Ukulinganiselwa kunye nokuthelekiswa nezinye izifundo ze-BRCA Survival Studies
Ucwaningo luka-2018 olukhankanywe apha ngasentla lukhuthaze kodwa lube nemingcele ebalulekileyo xa ubujonge ukusinda kunye ne-BRCA.
Ubudala: Uphando lukhangeleke kuphela kwabasetyhini abangaphantsi kweminyaka engama-40, kwaye kukho ukubaluleka okubalulekileyo phakathi kwabasetyhini abasetyhini abanomdlavuza wesibeleko kunye nabasetyhini abadala. Asiyazi ukuba ezi ziphumo ziya kuba zifanayo xa abafazi abadala belifaniswa.
Ubude bexesha lokufunda: Enye ingxaki nge-2018 isifundo kukuba ilandele kuphela abafazi iminyaka eyi-10. Abasetyhini abaneenguquko ze-BRCA banakho amathuba okuba bavelise umdlavuza wesibeleko wesibini kwezinye ibele ezingenza umehluko emva kwexesha elingu-10 lokufunda.
Isifundo esasilandelayo esilandela abasetyhini ngomhlaza wesifuba sokuqala (isigaba soku-1 kunye no-2) kunye ne-BRCA1 kunye ne-BRCA2 ukuguqulwa kweminyaka engama-20 kubonise ukunyuka kwenyameko kwabasetyhini abanomdla wokuhlalisana (ukususwa kwesifuba esingenayo umdlavuza). Enyanisweni, ukuba ne-double mastectomy iyancipha ingozi yokufa kwaba bafazi ngexesha eliphakathi kweminyaka eyi-10 ukuya kwe-20 emva kokuxilongwa.
Uninzi lwabantu abafa ngalolo xesha bephakathi kwabantu abaye bahlakulela umdlavuza wesibeleko wesibeleko kwisibini. Isiqingatha sithuba sithuba phakathi kokuphuhliswa komdlavuza wokuqala webele kunye nesibini (engahambelananga) nomhlaza wesifuba uneminyaka engama-5.7. Olu pho nonongo luqinisekisile ukuba ukuphonononga iindlela ezintle zokwenza unyango kunokufuna iimfuno zexesha elide.
Uhlobo lotyando: Uhlobo lotyando olwenziwa ngumfazi onokuguqulwa kwe-BRCA, njengoko kuphawulwe kwisifundo esiphezulu ngasentla, kunokukwenza umehluko. Ngophando luka-2018, kwakungekho umahluko ekusindeni phakathi kwabantu abane-lumpectomy okanye abo babe ne-mastectomy okanye i-mastectomy kabini. Oku kuyahluka uma abafazi belandelwa ngaphaya kweminyaka eyi-10. Ekubeni abaninzi balaba bafazi banokulindela ukuba baphile iminyaka emininzi, oku kubalulekile ukuqaphela.
Olunye unyango lunokuchaphazela nokuphila. Uphononongo olwenziwa ngo-2013 lwafumanisa ukuba ukusinda kwakufana phakathi kwe-BRCA kunye ne-BRCA abasetyhini abangenanto kwiminyaka eyi-10. Nangona kunjalo, olo cwaningo lufumene ukuba ngabafazi abaneengxaki ze-BRCA1 kunye nomhlaza wesifuba wexesha lokuqala, ukususa ama-ovari kunye nama-tublopian tubes (oophorectomy). Ezinye izifundo ziye zaphawula oku kuphucuka kwindlela yokuphila kunye ne-oophorectomy.
Uvavanyo lokuguquka komzimba: Njengoko kuphawuliwe kwangaphambili, ukuhlolwa kweentsholongwane zentsholongwane kusekusemncinci. Kubekho iziphumo ezingamanga kwisifundo njengoko iindlela ezahlukeneyo zokuvavanya zisetyenzisiwe.
Eminye imingcipheko yeso sifundo: Esinye isifundo esifumene ukuba izinga lokusinda kweengculaza zesifuba liphezulu kakhulu kulabo babe neinguqulelo ze-BRCA kodwa kwakukho okunye okungafaniyo. Abafazi baseAshkenazi ilifa lamaYuda kunye nalabo abanomdlavuza webele we-metastatic babenomlinganiselo omncinci wokusinda xa i-BRCA ichanekile.
Abaxhobayo: Ucwaningo lwe-2018 lukhankanywe ngokubhekiselele kwabo abangenayo umdlavuza wesibele. Kubalulekile ukuba uqaphele ukuba injongo yocwaningo yayikujongana nokusinda kwabasetyhini ababenomdlavuza webele kunye ne-BRCA. Olu pho nonongo aluzange lujonge "abachasayo," eli gama elisetyenziselwa ukuchaza abafazi abaneenguquko ze-BRCA abasengozini kodwa bengenayo umdlavuza webele.
ILizwi
Abantu abaninzi baye babuza ukuba ngaba abaguquguqukayo be-BRCA banokungafani phakathi kwabo banomdlavuza ongenalo ifa. Ucwaningo lwango-2018 lwaluqinisekisa ngandlela-thile, kodwa ixesha elide lokuvavanya lifuneka ukuba ukwazi ukuba ngaba kukho ukungafani kunye nokufumanisa ukhetho oluchanekileyo lwabesetyhini abanomdlavuza webele we-BRCA. Kakade ke, kukho ezininzi izinto ezingaphaya kokusinda ekufuneka zihlolwe xa zijonga unyango.
Ukujonga ezi zifundo, kuyacaca ukuba sinokuningi okunokukufunda malunga nomhlaza wesifuba. Enyanisweni, sisasazi nto malunga neenguqu ezingezantsi ze-BRCA eziguquka kwimizimba kunye nomngcipheko wesifo somhlaza.
Ukuba uye wafumanisa ukuba unomdlavuza webele, thatha ixesha lokuphanda umhlaza wakho . Ukuguqulwa kwamachiza ngokukhawuleza kubalulekile ukuba wonke umntu abe ngummeli wakhe ekunyamekelweni komhlaza . Wonke amabhinqa ahlukileyo kwaye unyango olungcono kumfazi omnye lungafanelanga elinye. Kubalulekile ukuba umfazi ngamnye afunyanwe nesifo ukuba akhethe unyango olulungele ukuba yena yedwa kwaye ahloniphe iimfuno zakhe.
> Imithombo:
> Baretta, Z., Mocellin, S., Goldin, E., Olopade, O., no-D. Huo. Impembelelo ye-BRCA Ukutshintshiselwa kweNtsholongwane kwi-Breast Cancer Prognosis: UkuHlola okuHlolo kunye neMeta-Uhlalutyo. Amachiza (iBaltimore) . 2016. 95 (40): e4975.
> Copson, E., Maishman, T., Tapper, W. et al. I-Germline BRCA Ukuguquguquka nokuPhumela kwiCancer-Onset ye-Breast Cancer (POSH). Lancet Oncology . Ipapashwe ngo-11 Januwari 2018.
> Metcalfe, K., Gershman, S., Ghadirion, P. et al. I-Contralateral Mastectomy kunye Nokusinda Emva kweNtsholongwane kaBestile kwizithuthi ze-BRCA1 kunye ne-BRCA2 Utshintsho: Ukuhlaziywa kwe-Restrospective. BMJ . 2014. 348: 226.
> Metcalfe, K., Lynch, H., Foulkes, W. et al. Impembelelo ye-Oophorectomy kwi-Survival Emva kweCarcer Breast kwi-BRCA1 kunye ne-BRCA2 Mutation Carriers. JAMA Oncology . 2015. 1 (3): 306-13.
> Templeton, A., Gonzalez, L., Vera-Badillo, F. et al. Ukusebenzisana Phakathi kobuhlobo beRormonal Receptor, Ubudala kunye Nokusinda kwiMonde kunye ne-BRCA1 / 2 Inguqulelo yeGerman: UkuHlola okuSingqinisisiweyo kunye ne-Meta-Regression. PLoS One . 2016. 11 (5): e0154789.