A1 Refereed original research article in a scientific journal
Germline variation at 8q24 and prostate cancer risk in men of European ancestry
Authors: Matejcic M, Saunders EJ, Dadaev T, Brook MN, Wang K, Sheng X, Al Olama AA, Schumacher FR, Ingles SA, Govindasami K, Benlloch S, Berndt SI, Albanes D, Koutros S, Muir K, Stevens VL, Gapstur SM, Tangen CM, Batra J, Clements J, Gronberg H, Pashayan N, Schleutker J, Wolk A, West C, Mucci L, Kraft P, Cancel-Tassin G, Sorensen KD, Maehle L, Grindedal EM, Strom SS, Neal DE, Hamdy FC, Donovan JL, Travis RC, Hamilton RJ, Rosenstein B, Lu YJ, Giles GG, Kibel AS, Vega A, Bensen JT, Kogevinas M, Penney KL, Park JY, Stanford JL, Cybulski C, Nordestgaard BG, Brenner H, Maier C, Kim J, Teixeira MR, Neuhausen SL, De Ruyck K, Razack A, Newcomb LF, Lessel D, Kaneva R, Usmani N, Claessens F, Townsend PA, Dominguez MG, Roobol MJ, Menegaux F, Khaw KT, Cannon-Albright LA, Pandha H, Thibodeau SN, Schaid DJ, Wiklund F, Chanock SJ, Easton DF, Eeles RA, Kote-Jarai Z, Conti DV, Haiman CA
Publisher: NATURE PUBLISHING GROUP
Publication year: 2018
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: ARTN 4616
Volume: 9
First page : 1
Last page: 11
Number of pages: 11
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-06863-1
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/37023883
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 x 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 similar to 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.
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