A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

一项针对全基因组关联研究的荟萃分析，旨在识别与侵袭性和非侵袭性前列腺癌相关的易感基因位点

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作者：Amin Al Olama,Ali,Kote-Jarai,Zsofia,Schumacher,Fredrick R,Wiklund,Fredrik,Berndt,Sonja I,Benlloch,Sara,Giles,Graham G,Severi,Gianluca,Neal,David E,Hamdy,Freddie C,Donovan,Jenny L,Hunter,David J,Henderson,Brian E,Thun,Michael J,Gaziano,Michael,Giovannucci,Edward L,Siddiq,Afshan,Travis,Ruth C,Cox,David G,Canzian,Federico,Riboli,Elio,Key,Timothy J,Andriole,Gerald,Albanes,Demetrius,Hayes,Richard B,Schleutker,Johanna,Auvinen,Anssi,Tammela,Teuvo L J,Weischer,Maren,Stanford,Janet L,Ostrander,Elaine A,Cybulski,Cezary,Lubinski,Jan,Thibodeau,Stephen N,Schaid,Daniel J,Sorensen,Karina D,Batra,Jyotsna,Clements,Judith A,Chambers,Suzanne,Aitken,Joanne,Gardiner,Robert A,Maier,Christiane,Vogel,Walther,Dörk,Thilo,Brenner,Hermann,Habuchi,Tomonori,Ingles,Sue,John,Esther M,Dickinson,Joanne L,Cannon-Albright,Lisa,Teixeira,Manuel R,Kaneva,Radka,Zhang,Hong-Wei,Lu,Yong-Jie,Park,Jong Y,Cooney,Kathleen A,Muir,Kenneth R,Leongamornlert,Daniel A,Saunders,Edward,Tymrakiewicz,Malgorzata,Mahmud,Nadiya,Guy,Michelle,Govindasami,Koveela,O'Brien,Lynne T,Wilkinson,Rosemary A,Hall,Amanda L,Sawyer,Emma J,Dadaev,Tokhir,Morrison,Jonathan,Dearnaley,David P,Horwich,Alan,Huddart,Robert A,Khoo,Vincent S,Parker,Christopher C,Van As,Nicholas,Woodhouse,Christopher J,Thompson,Alan,Dudderidge,Tim,Ogden,Chris,Cooper,Colin S,Lophatonanon,Artitaya,Southey,Melissa C,Hopper,John L,English,Dallas,Virtamo,Jarmo,Le Marchand,Loic,Campa,Daniele,Kaaks,Rudolf,Lindstrom,Sara,Diver,W Ryan,Gapstur,Susan,Yeager,Meredith,Cox,Angela,Stern,Mariana C,Corral,Roman,Aly,Markus,Isaacs,William,Adolfsson,Jan,Xu,Jianfeng,Zheng,S Lilly,Wahlfors,Tiina,Taari,Kimmo,Kujala,Paula,Klarskov,Peter,Nordestgaard,Børge G,Røder,M Andreas,Frikke-Schmidt,Ruth,Bojesen,Stig E,FitzGerald,Liesel M,Kolb,Suzanne,Kwon,Erika M,Karyadi,Danielle M,Orntoft,Torben Falck,Borre,Michael,Rinckleb,Antje,Luedeke,Manuel,Herkommer,Kathleen,Meyer,Andreas,Serth,Jürgen,Marthick,James R,Patterson,Briony,Wokolorczyk,Dominika,Spurdle,Amanda,Lose,Felicity,McDonnell,Shannon K,Joshi,Amit D,Shahabi,Ahva,Pinto,Pedro,Santos,Joana,Ray,Ana,Sellers,Thomas A,Lin,Hui-Yi,Stephenson,Robert A,Teerlink,Craig,Muller,Heiko,Rothenbacher,Dietrich,Tsuchiya,Norihiko,Narita,Shintaro,Cao,Guang-Wen,Slavov,Chavdar,Mitev,Vanio,Chanock,Stephen,Gronberg,Henrik,Haiman,Christopher A,Kraft,Peter,Easton,Douglas F,Eeles,Rosalind A
期刊：Human Molecular Genetics影响因子：3.200
时间：2013起止号：2013 Jan 15;22(2):408-15
doi：10.1093/hmg/dds425研究方向： 肿瘤
疾病类型： 前列腺癌

Abstract

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

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