Yiziphi I-Cancers Ebangelwa Ukuguqulwa Kwe-BRCA2 nokuthi Zivamile Kanjani?
Uma ufunde ukuthi uthwala ushintsho lwezakhi ze-BRCA2, noma uma ukhathazekile ungase, yini okudingeka ukwazi? I-BRCA2 ye-gene mutations ingandisa ingozi yomdlavuza webele kanye nezinye izicubu.
Izinguquko ze-BRCA2 zivame ukuhlanganiswa kanye nezinguquko ze-BRCA1, nokho kunemibono eminingi ebalulekile. Izinguquko ezimbili zenza izingozi ezihlukahlukene zomdlavuza webele kanye ne-ovarian futhi zihlotshaniswa ne-cancer ehlukile kwezinye izifunda zomzimba.
Isibonelo, umdlavuza we-pancreatic uvame kakhulu ngezinguquko ze-BRCA2.
Ukuqonda umehluko kulezi zinguquko kubalulekile ekuqondeni umlando womndeni wakho kanye. Udokotela wakho angase akhathazeke kakhulu uma unesihlobo esisodwa esiseduze esinesifo somdlavuza webele kanye nesinye somdlavuza we-pancreatic kunokuba ngabe unesifo somdlavuza webele. Umdlavuza we-Pancreatic awuvamile kakhulu kunomdlavuza wesifuba, futhi uma kwenzeka ngokuhambisana nomdlavuza wesifuba kuphakamisa ifulege ebonisa ukuthi ushintsho lwe-BRCA2 lukhona.
Incazelo
Ukubuyekezwa okusheshayo kwezakhi zofuzo kungenza izinguquko ze-BRCA zilula ukuyiqonda. I- DNA yethu yakhiwa ama-chromosomes angu-46, angu-23 kusuka kobaba bethu no-23 kusuka kumama. I-Genesini yizingxenye ze-DNA ezitholakala kuma-chromosomes ukuthi ikhodi yemisebenzi ethile. Zifana nesimiso umzimba osebenzisayo ukwenza amaprotheni. Lawa maprotheni abe nemisebenzi eminingi evela ku-hemoglobin egazini lakho elibopha umoya-mpilo, ukukuvikela emdlalweni.
Izinguquko zindawo zezakhi zofuzo ezimele. Lapho isakhi noma isakhiwo sengozini, iprotheni engavamile ingenziwa engasebenzi njengaleyo protheyini evamile. Kunezinhlobo eziningi ezahlukene zezinguquko ze-BRCA. I "khodi" ezakhiweni zofuzo isonakele uchungechunge lwezinhlamvu (ezaziwa ngokuthi izisekelo). Uchungechunge lwalezi zincwadi litshela umzimba wakho ukuthi ubeke ama-amino acids ezahlukene ukuze wenze amaprotheni.
Ngokujwayelekile isisekelo sisusiwe (ukususwa kwezinguquko), ngezinye izikhathi enye ingezwa, futhi ngezinye izikhathi izinyathelo eziningana zihlelwa kabusha.
Indlela I-Cancer Eyenziwa Ngayo
Igayela le-BRCA liyisakhi esiyingqayizivele okuthiwa i- tumor suppressor gene esinesisindo samaphrotheni esizosivikela ekuhlaleni umdlavuza.
Ukulimala (izinguquko kanye nezinye izinguquko zofuzo) kwenzeka ku-DNA yamaseli ethu nsuku zonke. Esikhathini esiningi, amaprotheni (afana nalawo aqoshwe kwi-BRCA isifo somzimba wegciwane lesisu) alungisa umonakalo noma aqede iseli elingavamile ngaphambi kokuba aqhubeke nenqubo yokuba ngumdlavuza. Ngezinguquko ze-BRCA2, noma kunjalo, la maprotheni awavamile, ngakho-ke lolu hlobo oluthile lokulungisa alukwenzeki (i-BRCA yokulungisa amaprotheni e-DNA ephindwe kabili).
Ukuvama
Ukushintshwa kwe-BRCA akuvamile. Izinguquko ze-BRCA1 zitholakala cishe ngamaphesenti angu-0.2 wabantu, noma abantu abangu-1 kubantu abangu-500. Izinguquko ze-BRCA2 zivame kakhulu futhi zitholakala kumaphesenti angu-0.45 wabantu, noma abantu abayi-222, nakuba kunezifundo ezinhlobonhlobo ezahlukene. Izinguquko ze-BRCA1 zivame kakhulu kulawo mafa ase-Ashkenazi amaJuda, kuyilapho i-BRCA2 inguquko eguquguqukayo.
Ubani Okufanele Ahlolwe?
Ngesikhathi samanje, akukhuthazwa ukuthi ukuhlolwa kwe-BRCA2 kwenziwe kubantu abaningi.
Esikhundleni salokho, labo abanomlando womuntu siqu noma womndeni wesifo somdlavuza bangase bafise ukucabangela ukuhlolwa uma iphethini nezinhlobo zomdlavuza zithola ukuthi ukuguqulwa kungase kube khona. Funda kabanzi mayelana nokuthi kufanele ucabangele ukuhlolwa kwe-BRCA .
Amakhansela abangela ukuguqulwa
Ukushintshwa kwe-BRCA2 kuhlukile kunezinguquko ze-BRCA1 (okuyizinto u-Angelina Jolie ayenayo futhi okukhulunywa ngaso kaningi) futhi kuphakamisa ingozi yezinhlobo ezahlukene zomdlavuza. Ngesikhathi samanje, ulwazi lwethu lusakhula futhi lokhu kungashintsha ngokuhamba kwesikhathi. Amanqamu ajwayelekile kakhulu kubantu abane-BRCA2 ukuguqulwa kuhlanganisa:
- Umdlavuza wesibeletho: Umdlavuza webeletho ngenxa ye-BRCA ukuguqulwa kwama-akhawunti ngamaphesenti angama-20 kuya kwangu-25 wegciwane lesandulela ngculazi. Abesifazane abanokuguqulwa kwe-BRCA2 banamathuba angu-45 okuthuthukisa umdlavuza webele ngaminyaka engu-70 (kancane kancane kunezinguquko ze-BRCA1). Amadoda anokuguqulwa kwe-BRCA2 nawo anomngcipheko ophakeme, kodwa lokhu kubungozi kuphela amaphesenti angu-1 kuphela. Abesilisa nabesilisa abanokuguqulwa kwe-BRCA nabo bathambekele ekuthuthukiseni umdlavuza webele ngesikhathi esincane.
- Umdlavuza we-Ovarian: Abesifazane abanokuguqulwa kwe-BRCA2 banamathuba angu-11 kuya ku-17 amathuba okuthuthukisa umdlavuza we-ovarian oneminyaka engu-70 (futhi ephansi kakhulu kunokushintshashintsha kwe-BRCA1). Abesifazane abanokuguqulwa kwe-BRCA2 bathambekele ekuhlakuleleni umdlavuza we-ovarian ngesikhathi esincane kunabesifazane abangenawo ushintsho.
- Umdlavuza we-prostate: Amadoda anezinhlobo zombili ze-BRCA1 ne-BRCA2 zingu-4.5 kuya kwezingu-83 amathuba okuba nomdlavuza wesibeletho. Labo abanezinguquko ze-BRCA2 (ngokungafani ne-BRCA1) bavame ukuhlakulela umdlavuza wesifo sofuba kanye nesilinganiso seminyaka engu-5 sokusinda singamaphesenti angama-50 (uma kuqhathaniswa namaphesenti angu-99 okulinganiselwa kweminyaka emihlanu emphakathini jikelele).
- Umdlavuza we-Pancreatic: Ingozi yomdlavuza we-pancreatic nayo yanda. Kulabo abahlakulela umdlavuza we-pancreatic, ukubuyekezwa okunye kwaphawula ukuthi ngenkathi ukusinda kulabo abane-BRCA2 ukuguqulwa komzimba kwakungaphansi kwalabo abahlakulela umdlavuza we-pancreatic sporadic, labo abanokushintshashintsha komzimba baphumelela kangcono nge-chemotherapy kunezintambo ezingezona ezithintekayo.
- Umdlavuza we-Lung: Asinalo ucwaningo oluningi ngomphumela we-BRCA2 wokuguqulwa komdlavuza emngeni wamaphaphu . Kwesinye isifundo, abesifazane ababhema futhi babe nokuguquguquka kwe-BRCA2 bekungaba amathuba amabili okuthuthukisa umdlavuza wamaphaphu kunabo abalingani babo abahlukumezayo.
- I-Leukemia: Abantu abane-BRCA1 zinguquko ababonakala bengenayo ukwanda kwe- leukemia . Ingozi ibonakala iphakanyisiwe kwabesifazane abane-BRCA2 ukuguqulwa kwemvelo okuye kwaba ne- chemotherapy yomdlavuza webele .
Ngokungafani nenengozi yokwanda komdlavuza wekoloni kwabanye abantu abane-BRCA1 yinguquko, isifundo esisodwa asizange sithole ingozi enkulu kulabo abane-BRCA2 yokuguqulwa kwezinguquko ezingaphezu kwalaba bantu jikelele. Ezinye izifundo zisekele lokhu okutholayo. Imihlahlandlela yokuhlola iphakanyisiwe ukuthi bonke abantu babe ne-colonoscopy yokuhlola (noma ukuhlolwa okufaniswayo) eneminyaka engu-50.
Abantu abathola ama-amabili amakhophi wegciwane le-BRCA2 elithintekile, ngaphezu kwamanqamu angenhla, amathuba okuba athuthukise izicubu eziqinile ebuntwaneni kanye ne-leukemia emilonyeni emangalisayo.
Ukunciphisa Ingozi Yokufa
Kunezinhlobo ezimbili zokuphatha ezihlukile kubantu abane-BRCA2, okubili okwenzelwe ukunciphisa amathuba okuthi umuntu uzofa ngenye yezinkinga zomdlavuza:
- Ukutholakala kokuqala: Ukutholakala kokuqala kuyinkqubo yokuzama ukuthola umdlavuza owenziwe ekuqaleni kwesigaba. Ngama-cancer amaningi, siyazi ukuthi ukusinda kuphakeme uma kutholakala esiteji sokuqala (isibonelo, isigaba 1 noma isigaba sesi-2) kunalokho uma kutholakala esikhathini esilandelayo (njengesigaba 4). Ngokutholwa kokuqala, umgomo ukuthola umdlavuza ngaphambi kokuthi kungabangela izimpawu ezizoholela ekutholeni kwawo. Asinayo izindlela zokuthola wonke amagciwane elesi sigaba sokuqala, futhi ukuhlolwa esinakho akuphelele. Isibonelo, abaningi baye bazwa ngabesifazane abanomdlavuza wesifuba naphezu kokuba benomzimba ovamile.
- Ukunciphisa Ingozi: Amasu okunciphisa ingozi asebenza ukunciphisa ingozi ukuthi umdlavuza uzokwakhiwa kuqala. Zenzelwe ukuvimbela umdlavuza ukuba ungenzeki. Izindlela zokunciphisa zingabandakanya ukuhlinzwa noma imithi (chemoprevention).
Iningi lezindlela ezisetshenziselwa izakhi zofuzo nomdlavuza zibandakanya ukuhlolwa noma ukunciphisa ingozi, kodwa kukhona ukuhlolwa okulodwa okungenza kokubili. I-colonoscopy ingasetshenziselwa ukuthola umdlavuza wekoloni ezinkathini zokuqala. Kodwa-ke, ingasetshenziswa ukunciphisa ingozi yomuntu othola umdlavuza uma i-polyp pre-cancerous itholakele futhi isusiwe ngaphambi kokuba ibe yingozi.
Ukuhlola nokuPhatha
Asinakho ukuhlola noma ukhetho lwezokwelapha kuzo zonke i-khansela ezixhunywe nezinguquko ze-BRCA2. Kusekuqaleni kwendlela yokunquma ukuthi yiziphi izindlela zokuhlola kanye nokwelapha okungcono kakhulu, ngakho-ke kubalulekile ukuba nodokotela onolwazi ekunakekeleni abathwali be-BRCA abaguquguqukayo. Ake sibheke okukhethwa kukho ngomdlavuza.
Umdlavuza webele
- Ukuhlola: Kuye ngomlando wakho wokuguqulwa nomndeni, ukuhlola ukuvame ukuqala ngesikhathi esincane kunabantu abangenawo ushintsho. Ukuhlola ukuhlolwa kungabandakanya i-mammography, i-MRI yebele, ne-ultrasound. Ama-mammograms anembile kakhulu kunabesifazane abasebasha ngenxa yobuningi bamabele abo kanye nama-MRIs ngokuvamile indlela ekhethiwe.
- I-Chemoprevention: Imithi ebizwa ngokuthi i-selecgen receptor modulators (SERMS) inganciphisa ingozi yokuthuthukisa umdlavuza webele kuze kube ngamaphesenti angu-50. Imithi etholakalayo ihlanganisa tamoxifen no- Evista (raloxifen) .
- Ukuhlinzwa: I-mastectomy ephakathi kwamanye amazwe inciphisa kakhulu ingozi yokuthuthukisa umdlavuza webele. Isikhathi sokuhlinzwa, kuncike ezintweni eziningi, kufaka phakathi izinhlelo zokuzala zokubeletha kanye nesifiso sokuncelisa.
I-Ovarian Cancer
- Ukuhlolwa: Okwamanje asikona indlela ehlolisisayo yokuhlola umdlavuza we-ovarian. Odokotela bangase bacabangele izivivinyo ezifana ne-ultrasound yangaphandle, izivivinyo zemitholampilo, ne-CA-125, kodwa asazi ukuthi ukuhlolwa okunjalo kuthuthukisa yini ukusinda.
- I-Chemoprevention: Ukusetshenziswa kwamaphilisi okulawula ukubeletha kunganciphisa ingozi yomdlavuza we-ovarian kuze kube ngamaphesenti angu-50 ngokusebenzisa isikhathi eside.
- Ukuhlinzwa: Ukususwa kwama-ovari nama-tublopian tubes ( salpingo-oophorectomy ) kunganciphisa ingozi yomdlavuza we-ovarian. Njengomdlavuza wesifuba ngemuva kwesisindo somzimba, abanye besifazane bangase babe nomdlavuza we-ovarian kodwa kungavamile kakhulu.
I-prostate Cancer
- Ukuhlolwa kwamanje komdlavuza wesifo sofuba kubangelwa ukuphikisana, kufaka phakathi ukuhlolwa kwe-PSA okuzungezile. Kulabo abathwala ukuguqulwa kwe-BRCA2, kubalulekile ukusebenza nodokotela we-urologist ojwayele isifo esinobudlova esitholakala emadodeni analezi zinguquko. Izikhombisi-ndlela zamanje zendawo yonke akufanele zilandelwe ngamadoda ane-BRCA2 ukuguqulwa kwamandla. I-American Society of Clinical Oncology iphakamisa i-PSA yonyaka kanye nokuhlolwa kwedijithali kusukela eneminyaka engu-40.
I-Cancer Pancreatic
- Asinayo imihlahlandlela ecacile ekuhlolweni komdlavuza we-pancreatic, nakuba ucwaningo lubonisa ukuthi ezigulini ezifanele (labo abangaphezu kweminyaka engu-50 futhi mhlawumbe abangu-60), ukuhlolwa kungase kuzuze
Izwi elivela
Abantu abathwala ukuguquguquka kwe-BRCA2 banomngcipheko owengeziwe wokuthuthukisa izinhlobo eziningana zomdlavuza. Kwezinye zazo, kunezinqubo zokuhlola ezingasiza ekuqaleni, kanye nezindlela zokuhlinza nezindlela zokwelapha zokunciphisa ingozi.
Ngokuqinisekile, indlela yokuphila enempilo ayikwazi ukugxila lapho ihlangene nenye yalezi zinguquko, njengoba sazi ukuthi ukuguqulwa kwe-BRCA akuqinisekisi ukuthi uzothola umdlavuza. Abantu abaningi babuza mayelana nokuhlolwa, kodwa ngesikhathi samanje ukuhlola kuphakanyiswa kuphela kulabo abanomlando womuntu siqu noma womndeni osho ukuthi ukuguqulwa kungase kube khona.
> Imithombo:
> I-American Society of Clinical Oncology Cancer.net. I-Hereditary Breast ne-Ovarian Cancer. Kubuyekezwe 07/17. https://www.cancer.net/cancer-types/hereditary-breast-and-ovarian-cancer
> Leao, R., Price, A., no R. James Hamilton. Ukuguqulwa kwe-Germline ye-BRCA kuma-Carrier-Ripe for Precision Oncology. I-prostate Cancer ne-Prostatic Disease . 2017 Dec 14. (Epub ngaphambi kokuphrinta).
> Maxwell, K., Domcheck, S., Nathanson, K. et al. Ukuphindaphinda kwabantu baseJalimane BRCA1 / 2 Izinguquko. I-Journal ye-Clinical Oncology . 2016. 34 (34): 4183-4185.
> National Cancer Institute. I-BRCA1 ne-BRCA2: Ingozi yeCanscer and Testing Genetics. https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet
> I-Library Kazwelonke Kazwelonke Yezokwelapha. I-Genetics Home Reference. I-BRCA2 yesakhi. Kubuyekezwe 01/23/18. https://ghr.nlm.nih.gov/gene/BRCA2