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

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.

SUBMITTER: Amin Al Olama A 

PROVIDER: S-EPMC3526158 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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

Amin Al Olama Ali A   Kote-Jarai Zsofia Z   Schumacher Fredrick R FR   Wiklund Fredrik F   Berndt Sonja I SI   Benlloch Sara S   Giles Graham G GG   Severi Gianluca G   Neal David E DE   Hamdy Freddie C FC   Donovan Jenny L JL   Hunter David J DJ   Henderson Brian E BE   Thun Michael J MJ   Gaziano Michael M   Giovannucci Edward L EL   Siddiq Afshan A   Travis Ruth C RC   Cox David G DG   Canzian Federico F   Riboli Elio E   Key Timothy J TJ   Andriole Gerald G   Albanes Demetrius D   Hayes Richard B RB   Schleutker Johanna J   Auvinen Anssi A   Tammela Teuvo L J TL   Weischer Maren M   Stanford Janet L JL   Ostrander Elaine A EA   Cybulski Cezary C   Lubinski Jan J   Thibodeau Stephen N SN   Schaid Daniel J DJ   Sorensen Karina D KD   Batra Jyotsna J   Clements Judith A JA   Chambers Suzanne S   Aitken Joanne J   Gardiner Robert A RA   Maier Christiane C   Vogel Walther W   Dörk Thilo T   Brenner Hermann H   Habuchi Tomonori T   Ingles Sue S   John Esther M EM   Dickinson Joanne L JL   Cannon-Albright Lisa L   Teixeira Manuel R MR   Kaneva Radka R   Zhang Hong-Wei HW   Lu Yong-Jie YJ   Park Jong Y JY   Cooney Kathleen A KA   Muir Kenneth R KR   Leongamornlert Daniel A DA   Saunders Edward E   Tymrakiewicz Malgorzata M   Mahmud Nadiya N   Guy Michelle M   Govindasami Koveela K   O'Brien Lynne T LT   Wilkinson Rosemary A RA   Hall Amanda L AL   Sawyer Emma J EJ   Dadaev Tokhir T   Morrison Jonathan J   Dearnaley David P DP   Horwich Alan A   Huddart Robert A RA   Khoo Vincent S VS   Parker Christopher C CC   Van As Nicholas N   Woodhouse Christopher J CJ   Thompson Alan A   Dudderidge Tim T   Ogden Chris C   Cooper Colin S CS   Lophatonanon Artitaya A   Southey Melissa C MC   Hopper John L JL   English Dallas D   Virtamo Jarmo J   Le Marchand Loic L   Campa Daniele D   Kaaks Rudolf R   Lindstrom Sara S   Diver W Ryan WR   Gapstur Susan S   Yeager Meredith M   Cox Angela A   Stern Mariana C MC   Corral Roman R   Aly Markus M   Isaacs William W   Adolfsson Jan J   Xu Jianfeng J   Zheng S Lilly SL   Wahlfors Tiina T   Taari Kimmo K   Kujala Paula P   Klarskov Peter P   Nordestgaard Børge G BG   Røder M Andreas MA   Frikke-Schmidt Ruth R   Bojesen Stig E SE   FitzGerald Liesel M LM   Kolb Suzanne S   Kwon Erika M EM   Karyadi Danielle M DM   Orntoft Torben Falck TF   Borre Michael M   Rinckleb Antje A   Luedeke Manuel M   Herkommer Kathleen K   Meyer Andreas A   Serth Jürgen J   Marthick James R JR   Patterson Briony B   Wokolorczyk Dominika D   Spurdle Amanda A   Lose Felicity F   McDonnell Shannon K SK   Joshi Amit D AD   Shahabi Ahva A   Pinto Pedro P   Santos Joana J   Ray Ana A   Sellers Thomas A TA   Lin Hui-Yi HY   Stephenson Robert A RA   Teerlink Craig C   Muller Heiko H   Rothenbacher Dietrich D   Tsuchiya Norihiko N   Narita Shintaro S   Cao Guang-Wen GW   Slavov Chavdar C   Mitev Vanio V   Chanock Stephen S   Gronberg Henrik H   Haiman Christopher A CA   Kraft Peter P   Easton Douglas F DF   Eeles Rosalind A RA  

Human molecular genetics 20121012 2

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 12  ...[more]

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