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; 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
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
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
Katso/Avaa
Lataukset: 

NATURE PUBLISHING GROUP
doi:10.1038/s41467-018-06863-1
Näytä kaikki kuvailutiedot
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.
Kokoelmat