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

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Matejcic, M, Saunders, EJ, Dadaev, T, Brook, MN, Wang, K, Sheng, X, Olama, AAA, 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 and Haiman, CA 2018 , 'Germline variation at 8q24 and prostate cancer risk in men of European ancestry' , Nature Communications, vol. 9, no. 1 , pp. 1-11 , doi: 10.1038/s41467-018-06863-1.

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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 -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.

Item Type: Article
Authors/Creators:Matejcic, M and Saunders, EJ and Dadaev, T and Brook, MN and Wang, K and Sheng, X and Olama, AAA and Schumacher, FR and Ingles, SA and Govindasami, K and Benlloch, S and Berndt, SI and Albanes, D and Koutros, S and Muir, K and Stevens, VL and Gapstur, SM and Tangen, CM and Batra, J and Clements, J and Gronberg, H and Pashayan, N and Schleutker, J and Wolk, A and West, C and Mucci, L and Kraft, P and Cancel-Tassin, G and Sorensen, KD and Maehle, L and Grindedal, EM and Strom, SS and Neal, DE and Hamdy, FC and Donovan, JL and Travis, RC and Hamilton, RJ and Rosenstein, B and Lu, YJ and Giles, GG and Kibel, AS and Vega, A and Bensen, JT and Kogevinas, M and Penney, KL and Park, JY and Stanford, JL and Cybulski, C and Nordestgaard, BG and Brenner, H and Maier, C and Kim, J and Teixeira, MR and Neuhausen, SL and De Ruyck, K and Razack, A and Newcomb, LF and Lessel, D and Kaneva, R and Usmani, N and Claessens, F and Townsend, PA and Dominguez, MG and Roobol, MJ and Menegaux, F and Khaw, KT and Cannon-Albright, LA and Pandha, H and Thibodeau, SN and Schaid, DJ and Wiklund, F and Chanock, SJ and Easton, DF and Eeles, RA and Kote-Jarai, Z and Conti, DV and Haiman, CA
Keywords: prostate cancer, genetics, risk, 8q24
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing Group
ISSN: 2041-1723
DOI / ID Number: 10.1038/s41467-018-06863-1
Copyright Information:

Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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