The Use of Genetic Markers to Determine Risk for Prostate Cancer at Prostate Biopsy

Abstract

Purpose: We examined a panel of 13 polymorphisms in 13 different genes to determine whether specific genotypes can help predict prostate cancer at the time of biopsy among men prescreened with prostate-specific antigen and digital rectal exam. Experimental Design: We examined 2,088 consecutive men who were referred for prostate biopsy from 1997 to 2003. Thirteen genes were examined, including TNF308, GSTT1, KLK2, endostatin, MCRA, MCRV, tyrosinase, MSR1, CHK2, RNasel, HOGG1-326, HOGG1-11657, and HRAS1. Odds ratio for detection of prostate cancer were adjusted for age, race, prostatespecific antigen, digital rectal exam, family history of prostate cancer, and urinary symptoms. Results: Of the 2,088 men, 996 (47.7%) had cancer detected. Four genes (TNF308, GSTT1, KLK2, and HOGG1-326) were significantly associated with prostate cancer. The adjusted odds ratios (OR) for prostate cancer for patients with the AA genotype of the TNF308 gene was 1.92 [95% confidence interval (95% CI), 1.0-1.5, P = 0.05], compared with those with the GG genotype, and for patients with theTTgenotype of the KLK2 gene, the OR was 1.5 (95% confidence interval, 1.0-2.2, P = 0.04), compared with the CC genotype. The OR for patients with a homozygous deletion of the GSTT1gene was 0.81 (95% CI, 0.6-1.0, P = 0.06) compared with those with the deletion, and the OR for patients with the GG genotype of the HOGG1-326 gene was 0.68 (95% CI, 0.5-1.0, P = 0.05) compared with the CC genotype. Patients who had all four alleles that were positively associated with prostate cancer had an OR of 9.33 (95% CI, 2.4-35.8, P = 0.0005) for prostate cancer compared with patients with alleles that were negatively associated with prostate cancer. Conclusions: Of the 13 polymorphisms, two were found to be positively associated with prostate cancer (TNF308 and KLK2) and two were negatively associated with prostate cancer (GSTT1 and HOGG1-326). Future studies are required to confirm these results.

Evaluation of Genetic Variations in the Androgen and Estrogen Metabolic Pathways as Risk Factors for Sporadic and Familial Prostate Cancer

“…Overall, these investigators showed that the GSTT1 polymorphism was unlikely to be the major determinant of susceptibility to prostate cancer. However, a recent large comprehensive study (n = 2088) reported a negative association between GSTT1 and prostate cancer (47). Cumulatively, these results suggest that polymorphisms in GSTT1 do not substantially increase the risk of prostate cancer in the population.…”

A genome-wide association screen identifies regions on chromosomes 1q25 and 7p21 as risk loci for sporadic prostate cancer

“…2 However, further case-control studies could not replicate the association. 9,15 We previously showed that the Arg462Gln SNP (rs486907) of the RNAsel gene was not associated with increased prostate cancer risk among our cohort. 9 The rs4568789 and 1830293 SNPs are within 1000 kb of each other at 1q25, and rs1930293 lies within 200 kb of the RNAsel gene.…”

“…9,15 We previously showed that the Arg462Gln SNP (rs486907) of the RNAsel gene was not associated with increased prostate cancer risk among our cohort. 9 The rs4568789 and 1830293 SNPs are within 1000 kb of each other at 1q25, and rs1930293 lies within 200 kb of the RNAsel gene. From high-resolution physical and transcription mapping studies between 1q25 and q31, Carpten et al identified at least 136 new STSs from the HPC1 region.…”

“…Study subjects were drawn from a consecutive sample of 3270 eligible men referred between 1998 and 2005 to two Prostate Centers at the University of Toronto because of a PSA value greater than or equal to 4.0 ng ml À1 . 9 No subject had a previous history of cancer and all subjects underwent one or more prostate biopsies to determine the presence of cancer. All patients agreed to participate in this study after informed consent, approved by the local Research Ethics Board.…”

“…9 Of the SNPs found to be positively associated with prostate cancer among the 2160 men, tagSNPs across each of the loci were selected from the International HapMap Database (http://www.hapmap.org) and genotyped the initial set of 2160 subjects, and an additional 930 subjects (total of 1454 cases and 1636 controls, total n ¼ 3090). Tag SNPs were selected using the multimarker method.…”