生物谷報道：英國科學(xué)家最近進行的一項大規(guī)模遺傳研究,，確定出了4種顯著影響女性患乳腺癌風(fēng)險的新的基因。該研究成果5月27日在線發(fā)表于《自然》雜志上,。
乳腺癌是女性健康的巨大“殺手”,，全球每年有50萬婦女死于這種癌癥。長期以來,，科學(xué)家知道遺傳因素對乳腺癌有很大的影響,，但到目前為止，所知的基因只占整個風(fēng)險因素的四分之一,。
在新的研究中,，英國劍橋大學(xué)的Douglas Easton和同事對4400位患有乳腺癌女性和4300位健康女性的基因組進行了對比分析，發(fā)現(xiàn)了單DNA堿基對上的30個不同之處,。通過進一步研究,，科學(xué)家確定出了4個與乳腺癌顯著相關(guān)的基因。
在4個新發(fā)現(xiàn)的基因中,，有3個參與調(diào)控細(xì)胞的生長,，其中關(guān)聯(lián)最強的是成纖維細(xì)胞生長因子受體II（fibroblast growth factor receptor 2，簡稱FGFR2）,。
Easton和同事發(fā)現(xiàn),，大約有16%的女性擁有FGFR2基因的兩個高風(fēng)險副本，這使得她們患乳腺癌的風(fēng)險比其他人高出了60%,。
目前新發(fā)現(xiàn)的癌癥基因還只是“冰山一角”,。Easton說，“即使最終確定出數(shù)百種風(fēng)險基因,，我也絲毫不會感到驚訝,。”不過，隨著越來越多的遺傳風(fēng)險因素被確定,，人類最終將會看到“全景”,，而相應(yīng)的風(fēng)險檢測和治療也會變得更加準(zhǔn)確。
原始出處:
Nature advance online publication 27 May 2007 | doi:10.1038/nature05887; Received 9 February 2007; Accepted 30 April 2007; Published online 27 May 2007
Genome-wide association study identifies novel breast cancer susceptibility loci
Douglas F. Easton1, Karen A. Pooley2, Alison M. Dunning2, Paul D. P. Pharoah2, Deborah Thompson1, Dennis G. Ballinger3, Jeffery P. Struewing4, Jonathan Morrison2, Helen Field2, Robert Luben5, Nicholas Wareham5, Shahana Ahmed2, Catherine S. Healey2, Richard Bowman6The SEARCH collaborators and , Kerstin B. Meyer7, Christopher A. Haiman8, Laurence K. Kolonel9, Brian E. Henderson8, Loic Le Marchand9, Paul Brennan10, Suleeporn Sangrajrang11, Valerie Gaborieau10, Fabrice Odefrey10, Chen-Yang Shen12, Pei-Ei Wu12, Hui-Chun Wang12, Diana Eccles13, D. Gareth Evans14, Julian Peto15, Olivia Fletcher16, Nichola Johnson16, Sheila Seal17, Michael R. Stratton17,18, Nazneen Rahman17, Georgia Chenevix-Trench19, Stig E. Bojesen20, Børge G. Nordestgaard20, Christen K. Axelsson21, Montserrat Garcia-Closas22, Louise Brinton22, Stephen Chanock23, Jolanta Lissowska24, Beata Peplonska25, Heli Nevanlinna26, Rainer Fagerholm26, Hannaleena Eerola26,27, Daehee Kang28, Keun-Young Yoo28,29, Dong-Young Noh28, Sei-Hyun Ahn30, David J. Hunter31,32, Susan E. Hankinson32, David G. Cox31, Per Hall33, Sara Wedren33, Jianjun Liu34, Yen-Ling Low34, Natalia Bogdanova35,36, Peter Schürmann36, Thilo Dörk36, Rob A. E. M. Tollenaar37, Catharina E. Jacobi38, Peter Devilee39, Jan G. M. Klijn40, Alice J. Sigurdson41, Michele M. Doody41, Bruce H. Alexander42, Jinghui Zhang4, Angela Cox43, Ian W. Brock43, Gordon MacPherson43, Malcolm W. R. Reed44, Fergus J. Couch45, Ellen L. Goode45, Janet E. Olson45, Hanne Meijers-Heijboer46,47, Ans van den Ouweland47, André Uitterlinden48, Fernando Rivadeneira48, Roger L. Milne49, Gloria Ribas49, Anna Gonzalez-Neira49, Javier Benitez49, John L. Hopper50, Margaret McCredie51, Melissa Southey50, Graham G. Giles52, Chris Schroen53, Christina Justenhoven54, Hiltrud Brauch54, Ute Hamann55, Yon-Dschun Ko56, Amanda B. Spurdle19, Jonathan Beesley19, Xiaoqing Chen19kConFab and AOCS Management Group and , Arto Mannermaa118,119, Veli-Matti Kosma118,119, Vesa Kataja118,120, Jaana Hartikainen118,119, Nicholas E. Day65, David R. Cox63 & Bruce A. J. Ponder62,67
Correspondence to: Douglas F. Easton1 Correspondence and requests for materials should be addressed to D.F.E. (Email: [email protected]).
Abstract
Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10-7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.
