CYP17,SRD5A2,CYP1B1, andCYP2D6Gene Polymorphisms with Prostate Cancer Risk in North Indian Population

Abstract

To investigate the involvement of the CYP17, SRD5A2, CYP1B1, and CYP2D6 variants with prostate cancer, a case-control study of 100 patients and an equal number of age-matched control men was conducted. There appears to be a nonsignificant increase with risk of prostate cancer for individuals carrying one copy of the CYP17 A2 allele (OR, 1.80; 95% CI, 0.99-3.29, P=0.05). The risk was increased in individuals having two A2 alleles (OR; 2.81, 95% CI, 1.06-7.40, P=0.03). Compared with men having the VV genotype of SRD5A2 gene, there was no significant association between the VL genotype and the risk of prostate cancer (OR; 0.54, 95% CI; 0.29-1.03, P=0.06). There was no difference in the occurrence of the genotype LL between controls and prostate cancer patients (OR; 0.90, 95% CI; 0.43-1.89, P=0.79). There was a nonsignificant increased risk of prostate cancer for individuals carrying the CYP1B1Leu/Val genotype (OR, 1.70, 95% CI, 0.91-3.17, P =0.09), which was increased in those having the Val/Val allele (OR, 3.38; 95% CI, 1.13-10.07, P=0.02). Relative to men homozygous for the wild-type allele in CYP2D6 gene, those heterozygous for the B allele had an odds ratio of 1.78 (95% CI, 0.76-4.17, P=0.18) for patients, and for homozygous individuals, it was 1.95 (0.55-6.93, P=0.30). These observations have suggested that the CYP17 A2/A2, CYP1B1 Val/Val, and CYP2D6 genotypes may be associated with an altered risk of prostate cancer, while the CYP2D6 and SRD5A2 V89L polymorphism have no association with its risk in the North Indian population.

Prostate cancer risk and aggressiveness associated with the CYP1B1 4326C/G (Leu432Val) polymorphism: a meta-analysis of 2788 cases and 2968 controls

“…Several polymorphic sites within the CYP1B1 gene (rs2617266, rs2567206, rs2551188, rs10012, rs1056836, rs1056827 and rs1800440) have been studied, but the rs1056836 (4326C/G, Leu432Val or L432V) site has been reported most frequently, albeit inconsistently, associated with increased PCa risk. [9][10][11][12][13][14][15] Some researchers have investigated the relationship between the CYP1B1 4326C/G polymorphism and PCa aggressiveness, although the definitions of low and high aggressiveness are different among these research reports.…”

Cytochrome P450 17A1 and Catechol O-Methyltransferase Polymorphisms and Age at Lynch Syndrome Colon Cancer Onset in Newfoundland

“…The CYP17 c.-34T!C polymorphism has been examined extensively in breast cancer with earlier studies, suggesting an increased risk of disease from the C allele (16,17), whereas more recent studies and meta-analyses do not support this link (18,19). Evidence for a link between the CYP17 c.-34T!C polymorphism and cancers of the ovary (20), endometrium (21), and prostate (22,23) were similarly inconsistent and controversial. Landi et al (33) reported no association between the current COMT polymorphism and risk of sporadic colon cancer in a casecontrol study.…”

“…5 Common genetic polymorphisms have been reported to influence endogenous hormone levels (14,15). Polymorphisms in the sex steroid synthesis and metabolism genes cytochrome P450 17A1 (CYP17) and catechol O-methyltransferase (COMT) have been studied extensively in relation to risk of breast cancer (16 -19), and to a lesser extent, cancers of the ovary (20), endometrium (21), and prostate (22,23).…”

The role of CYP17A1 in prostate cancer development: structure, function, mechanism of action, genetic variations and its inhibition

“…A few epidemiologic studies have determined a positive association between this polymorphism and the Gleason score/clinical stage and serum PSA levels (Sobti et al 2006(Sobti et al , 2008 but many more conclusions are negative (Haiman et al 2001;Stanford et al 2002;Madigan et al 2003;Mononem et al 2006;Okugi et al 2006;Hamada et al 2007;Wright et al 2010;Risio et al 2011;Souiden et al 2011;Sivonova et al 2012;Yamada et al 2013;Han et al 2015;Henríquez-Hernández et al 2015;Brureau et al 2016;Song et al 2016). Some of the studies suggest that the CYP17A1 gene is a risk factor for PCa in males of advanced age (Souiden et al 2011;Song et al 2016).…”