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Germline variation at 8q24 and prostate cancer risk in men of European ancestry.

ABSTRACT: Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.

SUBMITTER: Matejcic M 

PROVIDER: S-EPMC6218483 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Germline variation at 8q24 and prostate cancer risk in men of European ancestry.

Matejcic Marco M   Saunders Edward J EJ   Dadaev Tokhir T   Brook Mark N MN   Wang Kan K   Sheng Xin X   Olama Ali Amin Al AAA   Schumacher Fredrick R FR   Ingles Sue A SA   Govindasami Koveela K   Benlloch Sara S   Berndt Sonja I SI   Albanes Demetrius D   Koutros Stella S   Muir Kenneth K   Stevens Victoria L VL   Gapstur Susan M SM   Tangen Catherine M CM   Batra Jyotsna J   Clements Judith J   Gronberg Henrik H   Pashayan Nora N   Schleutker Johanna J   Wolk Alicja A   West Catharine C   Mucci Lorelei L   Kraft Peter P   Cancel-Tassin Géraldine G   Sorensen Karina D KD   Maehle Lovise L   Grindedal Eli M EM   Strom Sara S SS   Neal David E DE   Hamdy Freddie C FC   Donovan Jenny L JL   Travis Ruth C RC   Hamilton Robert J RJ   Rosenstein Barry B   Lu Yong-Jie YJ   Giles Graham G GG   Kibel Adam S AS   Vega Ana A   Bensen Jeanette T JT   Kogevinas Manolis M   Penney Kathryn L KL   Park Jong Y JY   Stanford Janet L JL   Cybulski Cezary C   Nordestgaard Børge G BG   Brenner Hermann H   Maier Christiane C   Kim Jeri J   Teixeira Manuel R MR   Neuhausen Susan L SL   De Ruyck Kim K   Razack Azad A   Newcomb Lisa F LF   Lessel Davor D   Kaneva Radka R   Usmani Nawaid N   Claessens Frank F   Townsend Paul A PA   Gago-Dominguez Manuela M   Roobol Monique J MJ   Menegaux Florence F   Khaw Kay-Tee KT   Cannon-Albright Lisa A LA   Pandha Hardev H   Thibodeau Stephen N SN   Schaid Daniel J DJ   Wiklund Fredrik F   Chanock Stephen J SJ   Easton Douglas F DF   Eeles Rosalind A RA   Kote-Jarai Zsofia Z   Conti David V DV   Haiman Christopher A CA  

Nature communications 20181105 1

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10<sup>-15</sup>), including three risk variants that have yet to be reported. From a polygenic risk scor  ...[more]