NHNG KHAM PHA HIEN AI VE

GEN UNG TH VU

BS ANG C NGHIEM, M.D., FACS

Moi ngay, trung bnh co nam phu n quan Cam, California cht kinh hai that tan khi nghe thay bac s cho biet: " a b ung th vu ". T au nam cho en nay co khoang 1.820 phu n quan mac phai chng ghe gm nay.

Thong ke mi nhat cua Hiep hoi Ung Th Hoa Ky bao cao vao thang 1, 1996 cho biet so ngi c nh benh ung th vu hang nam tren at My la 185.700 ngi, gom 1.400 nam va 184.300 n. So t vong moi nam len ti 44.560 ngi ( 260 nam, 44.300 n ).

Nh a biet, phu n A Chau co ty so ung th vu thap neu co i song kieu ong A theo nh s tm hieu cua cac BS Bernstein, Henderson, Pike va Ross tng trnh vao nam 1980. Nhng mi ay, BS Pike va Anna Wu, thuoc ai Hoc Y Khoa USC a nhan thay ty so ay a cao gap hai phu n di dan goc A Chau tai Hoa Ky qua 15 nam khao sat. Co ngha la mot trong 20 ngi co the vng benh.

Ung th vu a c xep hang th hai sau ung th phoi giet hai phu n.

Nhng kham pha gan ay ve gen ung th, nhat la thuoc vu a khien nhng y hoc gia biet nhieu hn ve cau truc dang ung th va hy vong trong tng lai se co nhng phng thc ngan chan va chung nga.

GEN UNG TH

Vai tro cua gen hay di truyen to a c David von Hansemann khao sat t nam 1890 tren s phan bao cua nhng u ac tnh cho rang o la nhng nguyen do cau truc ung th. Nhng mai ti gan the ky sau, vao nam 1914 mi c Theodor Boveri trnh bay trong luan tap noi tieng Zur Frage der Entstehung maligner Tumoren gi y ve s ac tnh la ket qua bat quan bnh cua nhiem sac the trong te bao bnh thng. Gia thuyet the ot bien gay ung th a a ti quan niem can nguyen khi t te bao nhieinh nam 1970 a tr thanh mot cuoc cach mang quan trong trong s tm hieu tao san ung th bao. Trong nhng nam 1980, phan tch cot the a c ap dung cho nhng u ac. Nhng d kien tao san ung th bao c hoan tat vao nam 1990 da vao nhng kieu nhan e xep hang u ung th, va ngi ta hy vong se hoan tat phan biet c 50.000 loai e cong bo vao nam 2000.

Nhng ky thuat tuyet hao nay a khien cac khoa hoc gia hieu c gen to ung th va s di truyen xay tren he nhiem sac the. o chnh la yeu to quan trong ap dung vao chan benh lam sang, phong nga, tien lng trong y khoa.

GEN UNG TH VU

Vao cuoi nam 1994, vi ky thuat lien ket phan giai, mot vung nho nhanh dai cua nhiem sac the 17 a c nhan nh la gen troi gay ung th vu. Th nghiem da tren mau cua nhng gia nh co di truyen ung th vu. Mau a c phan tach DNA ( DeoxyriboNucleic Acid ) ghi dau v tr ch co nhng ngi a mac benh. Vung nhiem sac the 17 q 21 phan nh nay c mang ten BRCA 1 ( ky hieu breast cancer-1 ).

nhng gia nh co nguy to ung th vu cao, BRCA 1 chiem ti 50%. Nhng gia nh co va ung th vu va
ung th buong trng, BRCA 1 len ti 90%. Ngi co goc gen ot bien BRCA 1 co trien vong 50% phat trien ung th vu vao trc 50 tuoi, tang tien ti 80% vao tuoi 65. 10% b ung th buong trng vao tuoi 60 ( Easton va cong s ).

BRCA 1 la gen ln 10 lan hn loai gen khac. Ngi bnh thng cha 2 dang giong nhau BRCA 1. Ngi nao co s ot bien bat khuon BRCA 1 nh nhng gia nh co nguy to cao, th de phat ung th vu neu mot gen BRCA 1 b suy hoai.

Thang 12, 1995 mi ay, bao cao cua BS Micheal Stratton thuoc Vien Khao cu Ung Th tai Surrey, Anh quoc, cung BS. P. Andrew Futreal cua Trung Tam ai hoc Y Khoa Duke, N. Carolina, trong bao Nature a tm thay mot gen ung th vu khac co ten BRCA 2 chiem nhiem sac the 13q12-13

Hai loai gen nay hp lai a tao xac xuat len en 90% thay nhng ngi b di truyen ung th vu.

Trong khi o, BS Press cua Trung Tam Ung th Norris USC va BS Dennis Slamon,M.D., cua UCLA ang co cong trnh khao sat mot loai gen ung th mang ten HER-2/ neu . Gen nay c phat hien vao khoang gia nam 1980. Benh nhan co loai nay mang ung th vu de lan vao hach, co trieu chng lam sang qua xau va song sot qua ngan han. Nh the HER-2/ neu la nguy to de gay tai phat va can phai co hoa tr lieu manh hn loai thng dung.

UNG TH VU GIA TRUYEN

Ung th vu gia truyen ch chiem t 5-10% so vi nhng can nguyen ung th vu khac. 1% c ke co nguy to gia nh toi cao nh:
Qua nhieu ung th vu ho hang gan ( 3 hay nhieu hn )
Ung th nhieu hn mot the he ( do di truyen t troi ).
Na so phu n trong gia nh mac phai
Hai vu eu b.
Benh phat trc 15 tuoi.
Gia nh co nhieu trng hp ung thu buong trng.

Tuy nhien phai ke en s lien he kch tao ung th vu trong gia nh chi phoi bi nhieu yeu to khac na nh moi sinh, noi tuyen, gen to bat thng

Hnh vuong: nam thng. Hnh tron: n thng. Hnh tron am: n ung th vu hay buong trng. * : mang ot bien BRCA 1. Vet cheo: t vong.

Cc nguy to ung th vu trong gia nh di truyen vet t troi vi nhieu trng hp ung th vu va buong trng.

CHAN TRI MI VE GEN

Khi biet c cau truc cua gen va cua DNA xep at tren nhiem sac t va the cua nhan bao, mot chan tri mi a thc s m rong trong s cach mang cua sinh hoc noi chung va y hoc noi rieng. Trong bat c mot cuoc thao luan nao lien quan ti bao hoc, gen eu c a ra ban luan nh la mot van e cua the ky se lam thay oi s sinh ton cua con ngi trong tng lai. Mon gen hoc a la mot mon " nong " ( hot ) cua nhng sinh vien thch thu trong nganh khao cu hien nay.

Rieng noi ve gen ung th vu cung nh cac gen ung th khac cac chuyen gia a at ca mot ky vong t phong nga cho ti tr lieu lam sang.

Hang Myriad Genetics Inc. ,Salt Lake City, tuyen bo vao thang 12/ 1995 la a co chng trnh ieu che hon hp th nghiem da va gen to BRCA 1 va BRCA 2 e kham pha tien ung th vu di truyen.

Nhng phng phap phong nga ung th vu a c e cap ti va hng dan quan chung. Cat bo han vu khi chang may sinh trong gia toc co nguy to ung th vu toi cao. T kham vu hang thang. Chup hnh vu moi nam. Kham vu lam sang bi y s moi 4 - 6 thang. Dung hoa chat phong nga nh thuoc khang estrogen tamoxifen hoac retinoid N-4 hyroxyphenyl retanimide ( NSABP-P01, NCI-Milan, Royal Marsden ) nhng cac loai nay a c kiem chng th nghiem don dap tren the gii e hy vong c ap dung lam sang

Nhng khao cu gan ay nhat cho thay s hien dien cua P-glycoprotein, tao san gen MDR 1, a khien ung th vu quen ln mot so thuoc hoa chat tr lieu nh loai Doxorubicin va Taxol. BS Muggia cua trung tam Ung Th Norris ang th nghiem them vao mot so thuoc nh estramustine phosphat va PSC 833 vi hy vong chuyen hoa ngc lai hau qua protein, khien ung th bao khong the tranh ne thu thuoc.

Theo bao cao mi ay nhat cua BS David Wellisch thuoc ai Hoc UCLA trnh bay trong nhng ngay hoi thao cua Hiep Hoi Ung th Hoa Ky vao au nam nay tai San Francisco da tren 300 phu n theo doi chan kham tai khu ung th vu:

22% co trieu chng sau muon qua nang can san soc tr lieu.
40% buon lo khi co con hoac ch em b ung th vu.
a so tin rang ho se b ung th vu dau nguy to thc s ch cao hn ngi thng oi chut.

Rat nhieu thieu n khi thay me bi ung th vu a bo hoc. 60 phu n co me b ung th vu a gam va khong thch thu giao hp. Hau het a mang mac cam se mac benh ung th vu bat c luc nao. Ho can nhng ho tr va hng dan tan tnh.

Gen ung th vu di truyen la mot d kien mi nhat cua nen y hoc tan tien hien ai. Gen a tao c mot ky nguyen mi e con ngi co the hieu c nhng cau truc benh tat gay nen cac chng ac tnh nh ung th, mien dch, bam sinh Cung v the, a co gia thuyet mot mai con ngi co the thay oi gen, chuyen hoa theo y mnh muon th se bat benh, bat lao, bat diet.

BS ANG C NGHIEM,MD.,FACS

THAM KHAO:

Cancer statistics 1996 ( Jan-Feb, Vol. 46 )
The Woman at Increased Risk for Breast Cancer ( Bilimoria, MD, Morrow,MD.)
Breast Cancer News ( Winter 95/ 96 )
American Cancer Society Science Writers Seminar ( San Francisco 96 )
Second gene in breast cancer ( Nature 12/ 95 )
New Focus Breast Cancer ( USC/ Norris, Fall 95 )
Cancer Research Report ( City of Hope , Winter 96 )
Mayo Clinical Update ( Autumn 95 )
Chromosomes, Genes, and Cancer ( F. Mitelman, MD,PhD. Lund, Sweden )
Diseases of the Breast ( Harris, Lippman, Morrow, Hellman 1996 )
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