Faculty Collaboration Database

Germline variation at 8q24 and prostate cancer risk in men of European ancestry. Nat Commun 2018 Nov 05;9(1):4616

Date

11/07/2018

Pubmed ID

30397198

Pubmed Central ID

PMC6218483

DOI

10.1038/s41467-018-06863-1

Scopus ID

2-s2.0-85056250910 (requires institutional sign-in at Scopus site)   36 Citations

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 < 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.

Author List

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, Gago-Dominguez M, Roobol MJ, Menegaux F, Khaw KT, 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

Author

Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Case-Control Studies
Chromosome Mapping
Chromosomes, Human, Pair 8
Disease Susceptibility
Genetic Markers
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Male
Prostatic Neoplasms
Risk Assessment
Risk Factors