Ukusinda Ukuhlukana E-Hereditary Breast Cancer
Abantu abaningi baye bakhathazeka ngokuthi "izakhi zofuzo" noma umdlavuza webele wesifuba. Siyazi ukuthi ukuguqulwa kwe-BRCA kungandisa kakhulu ingozi yokuthuthukisa umdlavuza webele. Kodwa kulabo abathola umdlavuza webele , ukusinda kuqhathaniswa kanjani nalabo abathuthukisa umdlavuza webele kodwa abanalo ukuguqulwa kwesakhi? Manje sinezifundo eziningana ezibuke lo mbuzo.
Ngokuqinisekile, kuyesabeka ukwazi ukuthi uthwala enye yalezi zinguquko. Uma uphatha ukuguqulwa kwe-BRCA kungasho ukuhlolwa okuningi okunye, ukwenza izinqumo zenhliziyo, kanye nokwelashwa okulimazayo uma umdlavuza kufanele uthuthuke. Kodwa ucwaningo olusha mayelana nokuphila isikhathi eside nalezi zinguquko zinganciphisa ezinye zezinkathazo zakho.
Kubalulekile, Nokho, ukubheka lezi zifundo ngokugcwele. Ezinye izifundo zibuke ngabesifazane abasha kuphela. Abanye baye babheka ngezikhathi ezehlukene uma behlola ukusinda. Kodwa abanye baye bahlola ukuthi iziphi izinyathelo ezingase zithuthukise ukusinda ikakhulukazi kwabesifazane abanezinguquko ze-BRCA.
Ake siqale ngokubuyekeza izinguquko ze-BRCA, ukuthi kungani zibalulekile ekuthuthukiseni umdlavuza webele, nokuthi lezi khansela zingase zihluke kanjani kumdlavuza wesifuba ongewona owodwa, bese ukhuluma ngalokho esikufunde embonweni wokuphila.
I-BRCA Izinguquko-Incazelo kanye Nomsebenzi weGenesis ye-BRCA
Siyazi ukuthi umdlavuza uvame ukukhula emva kokuchungechunge kweDNA kwezakhi zofuzo ezenzekayo.
Izakhi zethu zofuzo zifana nepulani eliphethe umklamo wezinhlelo zamaprotheni ezenziwe emizimbeni yethu. Iziqondiso ezithathwa ngegciwane zinezikhombisi zokwenza amaprotheni avela kuma-enzyme aphula ukudla kwethu, kuma-proteins asebenza ukusikhulula umdlavuza.
Igama elithi mutation libhekisela kunoma yiluphi uhlobo lomonakalo ku-DNA olushintsha ukwakheka kwalo.
I-DNA yethu yakhiwa ama-chromosomes angu-46, angu-23 kusuka kumama no-23 kusuka kobaba. I-Genethi, futhi, izigaba zama-chromosomes ezithwala izinkomba zokukhiqiza amaprotheni athile. Lezi zikhombisi-ndlela zenziwe njengezinhlamvu zezinhlamvu (izigaba ezimbili) ezisebenza njengekhodi.
Uma izinhlamvu (izisekelo) ezakhiweni zihlanganisiwe, izikhombisi-ndlela zingaba zingalungile futhi ngaleyo ndlela zibe yipulani yesiprotheni engavamile. Ngezinye izikhathi izisekelo zinezelwa (izengezo), ngezinye izikhathi zisuswe (ukususwa kwezinguquko) futhi ngezinye izikhathi zihlelwa kabusha. (Kunezinye izinguquko ezingase zenzeke). Kwenzekani ngemuva kokuthi ukuguqulwa kwefa kutholakale noma kutholakale ngesikhathi somdala, kuncike ekusebenzeni kwesakhi sofuzo.
Ama-gène e-BRCA ama- gly suppressor amagciwane . I-code for proteins ezivimbela ukukhula kwezicubu ezifana nomdlavuza wesifuba nomdlavuza we-ovarian. Ngokuqondile, ikhodi ye-BRCA ikhodi yama-protein anesibopho sokulungisa umonakalo ku-DNA emasethini ethu (alungisa amakhefu ku-DNA kabili elinezintambo).
Ngamanye amangqamuzana ethu aqukethe amajethi amabili e-BRCA, ikhophi eyodwa kusuka kumama wethu kanye nekhophi eyodwa kubaba wethu. I-BRCA izakhi zofuzo ziyi-autosomal ngokweqile, okusho ukuthi kokubili amakhophi wegesi kumele ashintshwe ukuze umdlavuza uhlotshaniswe nokuguqulwa kwezakhi zofuzo.
Njengoba abantu abaningi badla igalelo elilodwa eliguquguqukayo (lokhu kubhalwe ngokuthi i-BRCA1 / 2), ukuguquguquka kwe-BRCA kwandisa ingozi yakho yomdlavuza ( ihambisana nesifo somdlavuza) kodwa akusho ukuthi uzoba nomdlavuza. Ukuze umdlavuza uqale elinye ikhophi yesakhi kuzodinga ukuguqulwa. Lokhu kuguqulwa kwesibili kuvame ukutholakala (kusuka ekulimaleni kwe-DNA ngenxa yemvelo, ukukhetha kokuphila, noma ukuguqula umzimba kwamaseli).
Kungaba ukudideka okukhulu uma sikhuluma ngalezi zinhlobonhlobo zezinguquko, nakuba kuchaza ukuthi kungani wonke umuntu onokuguquguquka kwe-BRCA ezoba nomdlavuza.
Izinguquko ezimbili eziholela emdlalweni webele emantwini iningi labesifazane abakwa-BRCA + futhi bahlakulele umdlavuza webele kunomthelela wokuguquka kwamagciwane kanye nokuguqulwa okutholakele.
- I-Germ-line noma iinguquko ezithathwe njengefa (lokhu kuhlanganisa ukuguqulwa kwe-BRCA njengoba kukhulunywe lapha) kudluliselwa kumama noma ubaba ukuya kwengane ekukhulelwe.
- Izinguquguquko zesimiso esincane noma ezitholakalayo (izinguquko ezenzeka ngenxa yomonakalo we-DNA ezihlobene nemvelo, izici zokuphila, noma ngisho nezinqubo ezivamile zamangqamuzana amangqamuzaneni) zenzeka nganoma yisiphi isikhathi ngesikhathi sokuphila komuntu.
(Kukhona nezakhi zofuzo ezihlobene nomdlavuza ezibizwa ngokuthi i-oncogenes ezizuzwe njengefa elihle kakhulu ukuze kutholakale ikhophi eyodwa yohlu oluguquguqukayo ukuze kuqhutshwe ukwanda komdlavuza, kodwa lokhu kungaphezu kwaleso sihloko).
Ukuqonda ukuguqulwa kwe-BRCA
Uma ukhuluma ngengozi yezinguquko ze-BRCA, kubalulekile ukuthi ukhombise ukuthi asikhulumi ngenguquko eyodwa ethize ku-DNA. Kunalokho kunamakhulu ngezindlela ezehlukene lapho ama-gene we-BRCA angashintshwa khona. Njengoba kuphawuliwe ngenhla, lezi zakhi zofuzo zingaba nesisekelo esengeziwe (incwadi), isisekelo esingekho, noma izisekelo zingabuyekezwa ngandlela-thile.
Kukhona ukungezwani komdlavuza phakathi kwe-BRCA1 ne-BRCA2 ukuguquka kwesimo somzimba, kanye nohlobo oluthile lokuguqulwa kwegazi olukhona esakhiweni. Ingozi enkulu yomdlavuza webele kwabesifazane ngaphandle kokuguqulwa kwe-BRCA ingamaphesenti angu-12. Kulabo abanokuguqulwa kwe-BRCA1, ingozi ephakathi kwamaphesenti angama-55 kuya kwangu-65 (futhi ingaba ngaphezu kwamaphesenti angu-87). Kulabo abanokuguqulwa kwe-BRCA2, cishe amaphesenti angu-45 abesifazane azokwakha umdlavuza webele nge-70 ubudala.
Umdlavuza we-Ovarian uvele cishe ngamaphesenti angu-1.3 abesifazane. Kulabo abanezinhlelo zokuguquka kwe-BRCA1, amaphesenti angu-39 kulindeleke ukuthi ahlakulele umdlavuza we-ovarian, kanti amaphesenti angu-11 kuya ku-17 alabo abane-BRCA2 ukuguqulwa kuzokuthuthukisa lesi sifo.
Kunamanye amagciwane ahlobene nokuguqulwa kwe-BRCA kanye nomdlavuza we-prostate, umdlavuza we-pancreatic, ngisho nomdlavuza wamaphaphu .
Ukwahlukana KwamaKhansela Okubeletha Kwabesifazane Ngezinguquko ze-BRCA
Kukhona umehluko phakathi kwamanqamu webele abesilisa phakathi kwabesifazane abanezinguquko ze-BRCA nalabo abangenalo ukuguqulwa kwezinto. Lokhu kubalulekile njengoba ezinye zalezi zingxabano zingase zilandele ukungezwani kokusinda.
Izinguquko ze-BRCA zivame kakhulu kubafazi abasebasha abathuthukisa umdlavuza webele. Kulabo abangaphansi kweminyaka engama-40, kucatshangwa ukuthi ngaphezulu kwamaphesenti angama-10 ekhansela ahlotshaniswa ne-BRCA enhle. Ngokuphambene nalokho, inani liseduze namaphesenti angu-5 kwabesifazane asebekhulile abanesifo.
Amagciwane ebelethwe ngabesifazane abano-BRCA abaguqulwayo bavame ukuba namanomdlavuza anezinga eliphakeme le- tumor . I-tumor grade isilinganiso sokuhlukumeza kwesisu.
Amagciwane ebeletha kwabesifazane abanezinguquko ze-BRCA (ikakhulukazi ze-BRCA1) zingaphansi kwe-receptor noma i-progesterone receptor. Futhi bancane amathuba okuba abe yi- HER2 enhle . Ama-hormone receptors , kanye ne-HER2, yi-receptors ebusweni bamangqamuzana omdlavuza webele lapho i-estrogen noma izici zokukhula zibophezela ukushayela inkambo yomdlavuza.
Ngamanye amazwi, amakhemikhali ebelethwe amathumba "amancane amathathu " ajwayelekile kubantu besifazane abanezinguquko ze-BRCA. Ngokuvamile, izifo zomdlavuza ezincelweni ezintathu ezingenayo ziyinselele kakhulu ukuphatha, njengoba izidakamizwa ze-hormonal noma ama-HER ezihlosiwe zizosebenza.
Ngomqondo omuhle, ukwelashwa kwamabele kubantu besifazane abane-BRCA ukuguqulwa kwezinto ezivame ukuphendula kangcono ku-neoadjuvant chemotherapy (i-chemotherapy enikezwe ngaphambi kokuhlinza) kunelabo abangenazo lezi zinguquko.
Ukushintshwa kwe-BRCA ne-non-BRCA ejwayelekile yomdlavuza webele (BRCAX)
Ngokuvame ukudideka ukukhuluma ngezinguquko ze-BRCA kanye nomdlavuza webele wesifo . Izinguquko ze-BRCA ziyimbangela yomdlavuza webele webele kodwa akuzona zonke izifo zomdlavuza ezibelethwe ngenxa yezinguquko ze-BRCA. Ngokuvamile, ukuguquguquka kwe-BRCA ku-20 kuya ku-25 wamaphesenti omdlavuza webele webele futhi amaphesenti angu-5 kuya ku-10 emdlavuza webele.
Amakhondomu e-Hereditary angeke ahlobene nokuguqulwa kwe-BRCA kuthiwa yi-non-BRCA yomdlavuza webele womndeni noma i-BRCAX. Izinguquko ze-Gene ezixhunywe nomdlavuza webele zihlanganisa nalawo ase-ATM CDH1, CHEK2, PALB2, PTKN, STK11, ne-TP53. Kukhona okungaphezulu okuningi okulindele ukutholakala, kepha ucwaningo lusesezinyathelo zokuqala.
Ukusinda Ngaphandle Kokungeniswa Kwe-BRCA (Ucwaningo luka-2018)
Uma ukhuluma ngokusinda nge-BRCA ukuguquka komzimba kubalulekile ukuqaphela ukuthi sikhuluma ngezibalo. Sinolwazi lokuthi umuntu "omaphakathi" onokuthi "isilinganiso" se-BRCA senze kanjani nomphumela wabo. Kodwa njengoba kunezinhlobonhlobo eziningi ezihlukile kulezi zinguquko, futhi abantu bakhetha izindlela ezahlukene zokuphatha umdlavuza wabo, izibalo azibikezeli imiphumela yabantu ngabanye. Abantu akuzona izibalo.
Ucwaningo olwenziwa ngo-2018 olushicilelwe eLancet Oncology lube yisifundo esikhulu sokuqhathanisa ukusinda komdlavuza webele kulabo abane-mutations we-BRCA abahlobene nalabo abanomdlavuza wesifuba we-sporadic. ekusindeni nomdlavuza wesifuba ohlobene nezinguquko ze-BRCA.
Iqembu labesifazane abaneminyaka engama-40 nangaphansi lilandelwa iminyaka eyi-10, ngokusinda kuhlolwe eminyakeni eyodwa, emihlanu, kanye neminyaka eyishumi emva kokuxilongwa. Ngemuva kweminyaka eyi-10, amazinga okusinda kulabo ababeyi-BRCA enhle ne-BRCA ababi befana. Eqinisweni, eminyakeni embalwa yokuqala, labo abane-BRCA nezinguquko zomzimba nomdlavuza wesifuba kathathu omuhle babe nemiphumela engcono kunalabo ababenesifo esinezintathu ezintathu ezimbi. Labo ababenokuguquguquka kwe-BRCA babe nethuba lokuba nesisindo samathambo amabili, kodwa kwakungafani umehluko phakathi kwalabo abanesisindo somzimba noma i-lumpectomy ne-radiation.
Ukulinganiselwa nokuqhathaniswa nezinye izifundo ze-BRCA Ukusinda
Ucwaningo luka-2018 olukhulunywe ngenhla lukhuthaze kodwa lube nokulinganiselwa okubalulekile uma sibheka ukusinda ne-BRCA eguqula umdlavuza webele.
Ubudala: Ucwaningo lubheka kuphela abesifazane abangaphansi kweminyaka engama-40, futhi kukhona ukungezwani okubalulekile phakathi kwabesifazane abasha abanekhansisi yebele kanye nabesifazane abakhulile abanesifo. Asazi ukuthi le miphumela izofana yini uma abesifazane asebekhulile beqhathaniswa.
Isikhathi sokutadisha: Inkinga eyodwa ngo-2018 isifundo ukuthi ilandele abesifazane kuphela iminyaka eyishumi. Abesifazane abanezakhi zomzimba ze-BRCA banamathuba amaningi okuthuthukisa umdlavuza wesifuba wesibili kwesinye isifuba esingase senze umehluko emva kwesikhathi sesifundo se-10.
Ucwaningo olude olwalandela abesifazane besifo somdlavuza wesifuba esisezingeni lokuqala (isigaba 1 no-2) kanye ne-BRCA1 ne-BRCA2 ukuguqulwa kweminyaka engama-20 kubonise ukunyuka okwenyuka kwabesifazane ababenesisindo esisodwa esisodwa (ukususwa kwesifuba esingenalo umdlavuza). Eqinisweni, ukuba ne-mastectomy kabili kunciphisa ingozi yokufa kulaba besifazane esikhathini esiphakathi kweminyaka engu-10 no-20 emva kokuxilongwa kwabo kokuqala.
Iningi labantu abafayo ngaleso sikhathi babephakathi kwabantu abaye baqala umdlavuza wesibeletho wesibeletho wesibili emathuneni abo. Isikhathi sesikhathi esiphakathi phakathi kokuthuthukiswa komdlavuza webele wokuqala kanye nomdlavuza wesibeletho wesibili (ongathinteki) wawuyiminyaka engu-5.7. Lolu cwaningo lwaqinisa umcabango wokuthi ukuhlola okukhethwa kukho okungcono kakhulu kungadinga izifundo zesikhathi eside.
Uhlobo lokuhlinza: Uhlobo lokuhlinzwa owesifazane onguquko lwe-BRCA oluqhutshwa, njengoba kuphawulwe esicwaningweni esiphezulu ngenhla, kungenza umehluko. Esifundweni sika-2018, kwakungekho umehluko ekusindeni phakathi kwabantu abane-lumpectomy noma labo abane-mastectomy noma i-mastectomy kabili. Lokhu kungaba okuhlukile uma abesifazane bebalandelwa ngaphesheya kweminyaka eyishumi. Ngenxa yokuthi abaningi balaba besifazane bangalindelwa ukuba baphile amashumi eminyaka, lokhu kubalulekile ukuphawula.
Ezinye zokwelapha zingathinta nokuphila. Ucwaningo olwenziwa ngo-2013 lwathola ukuthi ukusinda kwakufana phakathi kwe-BRCA kanye ne-BRCA abesifazane abangenayo eminyakeni eyishumi. Lelo cwaningo lathola ukuthi kubantu besifazane abanomdlavuza we-BRCA1 kanye nesifo somdlavuza wesifuba sokuqala, ukususa ama-ovari nama-tublopian tubes (oophorectomy) kuphuthumayo. Ezinye izifundo ziye zaphawula lokhu kuthuthukiswa ekusindeni nge-oophorectomy.
Ukuhlolwa komzimba: Njengoba kuphawuliwe ekuqaleni, ukuhlolwa kwezakhi zofuzo kusengumntwana. Kube khona imiphumela emibi kulolu cwaningo njengoba izindlela ezahlukene zokuhlolwa zisebenziswa.
Ezinye izici eziyingozi : Ucwaningo olulodwa oluthola ukuthi izinga lokusinda umdlavuza webele lomzimba lalingcono kakhulu kulabo ababenokushintshashintsha kwe-BRCA kodwa kunezimbalwa ezimbalwa. Amakhosikazi ase-Ashkenazi amaJuda nalabo abanomdlavuza webele we-metastatic babe nesilinganiso esincane sokusinda uma i-BRCA inempilo.
Abavikeli: Isifundo sika-2018 sishiwo ngokubhekisela kulabo abangenayo umdlavuza webele. Kubalulekile ukuphawula ukuthi injongo yocwaningo kwakuwukubuka ukusinda kwabesifazane abavele benomdlavuza webele kanye nokuguqulwa kwe-BRCA. Lolu cwaningo aluzange lubheke "abavimbela phambili," igama elisetshenziselwa ukuchaza abesifazane abaguquguqukayo be-BRCA abasengozini kodwa bengakabi nomdlavuza webele.
Izwi elivela
Abantu abaningi baye babuza ukuthi ngabe labo abanokuguqulwa kwe-BRCA banokuhlukana ekusindeni kulabo abanomdlavuza webele ongewona owamafa. Ucwaningo lwango-2018 lwaluqinisekisa ngezindlela ezithile, kepha isikhathi eside sokuhlolwa siyadingeka ukuze wazi ukuthi umehluko yini kanye nokukhetha ukwelashwa okuphumelelayo kakhulu kwabesifazane abanomdlavuza webele we-BRCA. Yiqiniso, kunezici eziningi ezingaphezu kokusinda okumelwe zihlolwe uma zibheke ukwelashwa.
Uma sicabanga ngalezi zifundo, kusobala ukuthi sinokuningi okumele sikufunde ngomdlavuza webele webele. Eqinisweni, asazi lutho ngezinguquko ezingezona ze-BRCA ezithinta izakhi zofuzo kanye nengozi yomdlavuza webele.
Uma uthola ukuthi unesifo somdlavuza webele, thatha isikhathi sokucwaninga umdlavuza wakho . Ngomuthi oguqukayo ngokushesha kangaka kubalulekile ukuba wonke umuntu abe ngummeli wakhe ekunakekeleni umdlavuza . Wonke owesifazane uhlukile futhi ukwelashwa okungcono kowesifazane oyedwa kungase kungabi okufanayo komunye. Kubalulekile ukuthi owesifazane ngamunye uthola ukuthi unesifo sokukhetha ukwelashwa okungcono kakhulu kuye kuphela futhi ukuhlonipha izifiso zakhe.
> Imithombo:
> Baretta, Z., Mocellin, S., Goldin, E., Olopade, O., noDo Huo. Umthelela we-BRCA Ukuguqulwa Kwama-Germine Ukuguqulwa Kwesifo Sebele Sebele: Ukubuyekezwa Okuhlelekile Nokuhlaziywa Kwe-Meta-Ukuhlaziywa. Imithi (Baltimore) . 2016. 95 (40): e4975.
> Copson, E., Maishman, T., Tapper, W. et al. Ukuguqulwa kwe-Germline BRCA ne-Impact ye-Young-Onset Breast Cancer (i-POSH): Isifundo se-Prospective Cohort. I-Lancet Oncology . Kushicilelwe ngo-11 Januwari 2018.
> Metcalfe, K., Gershman, S., Ghadirion, P. et al. I-Contralateral Mastectomy Nokusinda Ngemuva kweKhansa Yasebele Emithwaleni Ye-BRCA1 ne-BRCA2 Izinguquko: Ukuhlaziywa Kwe-Restrospective. BMJ . 2014. 348: 226.
> Metcalfe, K., Lynch, H., Foulkes, W. et al. Umphumela we-Oophorectomy ekusindeni Emva kweCanscer Breast ku-BRCA1 ne-BRCA2 Mutation Carriers. I-JAMA Oncology . 2015. 1 (3): 306-13.
> Templeton, A., Gonzalez, L., Vera-Badillo, F. et al. Ukusebenzisana Phakathi Kwezimo Zama-Hormonal Receptor, Age and Survival in Patient with BRCA1 / 2 Germline Mutations: Ukubuyekezwa Okuhlelekile kanye Nokunciphisa Amandla. PLoS One . 2016. 11 (5): e0154789.