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

Newcomb LF; Kaneva R; Grindedal EM; Conti DV; Wiklund F; Townsend PA; Brenner H; Al Olama AA; Pashayan N; Usmani N; Razack A; Maier C; Sheng X; Haiman CA; Berndt SI; Cancel-Tassin G; Kim J; Claessens F; Rosenstein B; Cannon-Albright LA; Thibodeau SN; Donovan JL; Stanford JL; Dominguez MG; Schaid DJ; Mucci L; Teixeira MR; Stevens VL; Maehle L; Schleutker J; Tangen CM; Roobol MJ; Chanock SJ; Strom SS; Wang K; Saunders EJ; Hamdy FC; Nordestgaard BG; Kraft P; Batra J; Penney KL; Khaw KT; Bensen JT; Hamilton RJ; Kogevinas M; Lu YJ; Kote-Jarai Z; Lessel D; Ingles SA; Gapstur SM; Easton DF; Cybulski C; Travis RC; Schumacher FR; Gronberg H; De Ruyck K; Matejcic M; Neuhausen SL; Clements J; Park JY; Eeles RA; Pandha H; Wolk A; Vega A; Koutros S; Benlloch S; Muir K; Dadaev T; West C; Sorensen KD; Govindasami K; Neal DE; Menegaux F; Kibel AS; Albanes D; Brook MN; Giles GG
Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Newcomb LF
Kaneva R
Grindedal EM
Conti DV
Wiklund F
Townsend PA
Brenner H
Al Olama AA
Pashayan N
Usmani N
Razack A
Maier C
Sheng X
Haiman CA
Berndt SI
Cancel-Tassin G
Kim J
Claessens F
Rosenstein B
Cannon-Albright LA
Thibodeau SN
Donovan JL
Stanford JL
Dominguez MG
Schaid DJ
Mucci L
Teixeira MR
Stevens VL
Maehle L
Schleutker J
Tangen CM
Roobol MJ
Chanock SJ
Strom SS
Wang K
Saunders EJ
Hamdy FC
Nordestgaard BG
Kraft P
Batra J
Penney KL
Khaw KT
Bensen JT
Hamilton RJ
Kogevinas M
Lu YJ
Kote-Jarai Z
Lessel D
Ingles SA
Gapstur SM
Easton DF
Cybulski C
Travis RC
Schumacher FR
Gronberg H
De Ruyck K
Matejcic M
Neuhausen SL
Clements J
Park JY
Eeles RA
Pandha H
Wolk A
Vega A
Koutros S
Benlloch S
Muir K
Dadaev T
West C
Sorensen KD
Govindasami K
Neal DE
Menegaux F
Kibel AS
Albanes D
Brook MN
Giles GG
Katso/Avaa
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NATURE PUBLISHING GROUP
doi:10.1038/s41467-018-06863-1
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042720337
Tiivistelmä
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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