Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases

• Published in: Human genetics 2015-04, Vol.134 (4), p.439-450
• Main Authors: Helfand, Brian T., Roehl, Kimberly A., Cooper, Phillip R., McGuire, Barry B., Fitzgerald, Liesel M., Cancel-Tassin, Geraldine, Cornu, Jean-Nicolas, Bauer, Scott, Van Blarigan, Erin L., Chen, Xin, Duggan, David, Ostrander, Elaine A., Gwo-Shu, Mary, Zhang, Zuo-Feng, Chang, Shen-Chih, Jeong, Somee, Fontham, Elizabeth T. H., Smith, Gary, Mohler, James L., Berndt, Sonja I., McDonnell, Shannon K., Kittles, Rick, Rybicki, Benjamin A., Freedman, Matthew, Kantoff, Philip W., Pomerantz, Mark, Breyer, Joan P., Smith, Jeffrey R., Rebbeck, Timothy R., Mercola, Dan, Isaacs, William B., Wiklund, Fredrick, Cussenot, Olivier, Thibodeau, Stephen N., Schaid, Daniel J., Cannon-Albright, Lisa, Cooney, Kathleen A., Chanock, Stephen J., Stanford, Janet L., Chan, June M., Witte, John, Xu, Jianfeng, Bensen, Jeannette T., Taylor, Jack A., Catalona, William J.
• Format: Article
• Language: English
• Subjects: Adult; African Americans; Aged; Aged, 80 and over; Biomedical and Life Sciences; Biomedicine; Cancer genetics; Chromosomes; Cohort Studies; Epidemiology; Gene Function; Genetic Association Studies; Genetic Predisposition to Disease; Genetics; Genomes; Health aspects; Health sciences; Human Genetics; Humans; Male; Metabolic Diseases; Middle Aged; Molecular Medicine; Mortality; National Cancer Institute (U.S.); Neoplasm Invasiveness; Original Investigation; Polymorphism, Single Nucleotide; Prostate cancer; Prostate specific antigen; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Public health; Risk Factors; Single nucleotide polymorphisms; Tumors; United States; Urology; Working groups
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-015-1534-9

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤6, 7, ≥8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69–0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68–0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58–0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54–0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (