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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.


ABSTRACT: Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

SUBMITTER: Al Olama AA 

PROVIDER: S-EPMC4383163 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.

Al Olama Ali Amin AA   Kote-Jarai Zsofia Z   Berndt Sonja I SI   Conti David V DV   Schumacher Fredrick F   Han Ying Y   Benlloch Sara S   Hazelett Dennis J DJ   Wang Zhaoming Z   Saunders Ed E   Leongamornlert Daniel D   Lindstrom Sara S   Jugurnauth-Little Sara S   Dadaev Tokhir T   Tymrakiewicz Malgorzata M   Stram Daniel O DO   Rand Kristin K   Wan Peggy P   Stram Alex A   Sheng Xin X   Pooler Loreall C LC   Park Karen K   Xia Lucy L   Tyrer Jonathan J   Kolonel Laurence N LN   Le Marchand Loic L   Hoover Robert N RN   Machiela Mitchell J MJ   Yeager Merideth M   Burdette Laurie L   Chung Charles C CC   Hutchinson Amy A   Yu Kai K   Goh Chee C   Ahmed Mahbubl M   Govindasami Koveela K   Guy Michelle M   Tammela Teuvo L J TL   Auvinen Anssi A   Wahlfors Tiina T   Schleutker Johanna J   Visakorpi Tapio T   Leinonen Katri A KA   Xu Jianfeng J   Aly Markus M   Donovan Jenny J   Travis Ruth C RC   Key Tim J TJ   Siddiq Afshan A   Canzian Federico F   Khaw Kay-Tee KT   Takahashi Atsushi A   Kubo Michiaki M   Pharoah Paul P   Pashayan Nora N   Weischer Maren M   Nordestgaard Borge G BG   Nielsen Sune F SF   Klarskov Peter P   Røder Martin Andreas MA   Iversen Peter P   Thibodeau Stephen N SN   McDonnell Shannon K SK   Schaid Daniel J DJ   Stanford Janet L JL   Kolb Suzanne S   Holt Sarah S   Knudsen Beatrice B   Coll Antonio Hurtado AH   Gapstur Susan M SM   Diver W Ryan WR   Stevens Victoria L VL   Maier Christiane C   Luedeke Manuel M   Herkommer Kathleen K   Rinckleb Antje E AE   Strom Sara S SS   Pettaway Curtis C   Yeboah Edward D ED   Tettey Yao Y   Biritwum Richard B RB   Adjei Andrew A AA   Tay Evelyn E   Truelove Ann A   Niwa Shelley S   Chokkalingam Anand P AP   Cannon-Albright Lisa L   Cybulski Cezary C   Wokołorczyk Dominika D   Kluźniak Wojciech W   Park Jong J   Sellers Thomas T   Lin Hui-Yi HY   Isaacs William B WB   Partin Alan W AW   Brenner Hermann H   Dieffenbach Aida Karina AK   Stegmaier Christa C   Chen Constance C   Giovannucci Edward L EL   Ma Jing J   Stampfer Meir M   Penney Kathryn L KL   Mucci Lorelei L   John Esther M EM   Ingles Sue A SA   Kittles Rick A RA   Murphy Adam B AB   Pandha Hardev H   Michael Agnieszka A   Kierzek Andrzej M AM   Blot William W   Signorello Lisa B LB   Zheng Wei W   Albanes Demetrius D   Virtamo Jarmo J   Weinstein Stephanie S   Nemesure Barbara B   Carpten John J   Leske Cristina C   Wu Suh-Yuh SY   Hennis Anselm A   Kibel Adam S AS   Rybicki Benjamin A BA   Neslund-Dudas Christine C   Hsing Ann W AW   Chu Lisa L   Goodman Phyllis J PJ   Klein Eric A EA   Zheng S Lilly SL   Batra Jyotsna J   Clements Judith J   Spurdle Amanda A   Teixeira Manuel R MR   Paulo Paula P   Maia Sofia S   Slavov Chavdar C   Kaneva Radka R   Mitev Vanio V   Witte John S JS   Casey Graham G   Gillanders Elizabeth M EM   Seminara Daniella D   Riboli Elio E   Hamdy Freddie C FC   Coetzee Gerhard A GA   Li Qiyuan Q   Freedman Matthew L ML   Hunter David J DJ   Muir Kenneth K   Gronberg Henrik H   Neal David E DE   Southey Melissa M   Giles Graham G GG   Severi Gianluca G   Cook Michael B MB   Nakagawa Hidewaki H   Wiklund Fredrik F   Kraft Peter P   Chanock Stephen J SJ   Henderson Brian E BE   Easton Douglas F DF   Eeles Rosalind A RA   Haiman Christopher A CA  

Nature genetics 20140914 10


Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants  ...[more]

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