Multiple loci identified in a genome-wide association study of prostate cancer

• DOI: 10.1038/ng.91
• Publication Date: 2008-02-10T19:13:57Z
• Authors: Gilles Thomas; Kevin B Jacobs; Meredith Yeager; Peter Kraft; Sholom Wacholder; Nick Orr; Kai Yu; Nilanjan Chatterjee; Robert Welch; Amy Hutchinson; Andrew Crenshaw; Geraldine Cancel-...; Brian J Staats; Zhaoming Wang; Jesus Gonzalez-Bo...; Jun Fang; Xiang Deng; Sonja I Berndt; Eugenia E Calle; Heather Spencer F...; Michael J Thun; Carmen Rodriguez; Demetrius Albanes; Jarmo Virtamo; Stephanie Weinstein; Fredrick R Schuma...; Edward Giovannucci; Walter C Willett; Olivier Cussenot; Antoine Valeri; Gerald L Andriole; E David Crawford; Margaret Tucker; Daniela S Gerhard; Joseph F Fraumeni; Robert Hoover; Richard B Hayes; David J Hunter; Stephen J Chanock
• Keywords: Male; Genetic Linkage; European Continental Ancestry Group; DNA Mutational Analysis; Quantitative Trait Loci; 610; Research Support; Polymorphism, Single Nucleotide; Linkage Disequilibrium; White People; N.I.H.; 03 medical and health sciences; Gene Frequency; Journal Article; Humans; Genetic Predisposition to Disease; Polymorphism; Non-U.S. Gov't; Intramural; Interleukin-16; 0303 health sciences; Genome; Genome, Human; Extramural; Chromosome Mapping; Prostatic Neoplasms; Single Nucleotide; Cadherins; Phosphoproteins; name=SDG 3 - Good Health and Well-being; 3. Good health; Case-Control Studies; /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; Human

We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 x 10(-13) and P < 2.14 x 10(-6)). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 x 10(-5)), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals.