Germline variation at 8q24 and prostate cancer risk in men of European ancestry.
View/ Open
Date
2018-11-05Author
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, Y-J
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
Gago-Dominguez, M
Roobol, MJ
Menegaux, F
Khaw, K-T
Cannon-Albright, LA
Pandha, H
Thibodeau, SN
Schaid, DJ
PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium,
Wiklund, F
Chanock, SJ
Easton, DF
Eeles, RA
Kote-Jarai, Z
Conti, DV
Haiman, CA
Type
Journal Article
Metadata
Show full item recordAbstract
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 × 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 ~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.
Collections
Subject
PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium
Chromosomes, Human, Pair 8
Humans
Prostatic Neoplasms
Disease Susceptibility
Genetic Predisposition to Disease
Genetic Markers
Risk Assessment
Risk Factors
Case-Control Studies
Chromosome Mapping
Genotype
Haplotypes
European Continental Ancestry Group
Male
Research team
Oncogenetics
Language
eng
Date accepted
2018-10-01
License start date
2018-11-05
Citation
Nature communications, 2018, 9 (1), pp. 4616 - ?
Publisher
NATURE PORTFOLIO
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
Related items
Showing items related by title, author, creator and subject.
-
Estimated impact of the COVID-19 pandemic on cancer services and excess 1-year mortality in people with cancer and multimorbidity: near real-time data on cancer care, cancer deaths and a population-based cohort study.
Lai, AG; Pasea, L; Banerjee, A; Hall, G; Denaxas, S; et al. (BMJ PUBLISHING GROUP, 2020-11-17)OBJECTIVES: To estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer. METHODS: We employed near real-time weekly data on cancer care to ... -
Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.
Glubb, DM; Thompson, DJ; Aben, KKH; Alsulimani, A; Amant, F; et al. (AMER ASSOC CANCER RESEARCH, 2021-01-01)BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and ... -
Can routine data be used to support cancer clinical trials? A historical baseline on which to build: retrospective linkage of data from the TACT (CRUK 01/001) breast cancer trial and the National Cancer Data Repository.
Kilburn, LS; Aresu, M; Banerji, J; Barrett-Lee, P; Ellis, P; et al. (BMC, 2017-11-23)BACKGROUND: Randomised clinical trials (RCTs) are the gold standard for evaluating new cancer treatments. They are, however, expensive to conduct, particularly where long-term follow-up of participants is required. Tracking ...