Germline variation at 8q24 and prostate cancer risk in men of European ancestry
- 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
- Haiman, CA
DOIAbstract
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 fa...
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