Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study

Abstract

BackgroundWe have previously shown that a functional polymorphism of the UGT2B15 gene (rs1902023) was associated with increased risk of prostate cancer (PC). Novel functional polymorphisms of the UGT2B17 and UGT2B15 genes have been recently characterized by in vitro assays but have not been evaluated in epidemiologic studies.MethodsFifteen functional SNPs of the UGT2B17 and UGT2B15 genes, including cis-acting UGT2B gene SNPs, were genotyped in African American and Caucasian men (233 PC cases and 342 controls). Regression models were used to analyze the association between SNPs and PC risk.ResultsAfter adjusting for race, age and BMI, we found that six UGT2B15 SNPs (rs4148269, rs3100, rs9994887, rs13112099, rs7686914 and rs7696472) were associated with an increased risk of PC in log-additive models (p < 0.05). A SNP cis-acting on UGT2B17 and UGT2B15 expression (rs17147338) was also associated with increased risk of prostate cancer (OR = 1.65, 95% CI = 1.00-2.70); while a stronger association among men with high Gleason sum was observed for SNPs rs4148269 and rs3100.ConclusionsAlthough small sample size limits inference, we report novel associations between UGT2B15 and UGT2B17 variants and PC risk. These associations with PC risk in men with high Gleason sum, more frequently found in African American men, support the relevance of genetic differences in the androgen metabolism pathway, which could explain, in part, the high incidence of PC among African American men. Larger studies are required.

Association between UDP‐glucuronosyltransferase 2B7 tagSNPs and breast cancer risk in Chinese females

“…Moreover, UGT1A1 polymorphisms are associated with the risk of ER− breast cancer . However, the present study indicates that there is no association between UGT2B7 polymorphisms and ER status in breast cancer, consistent with the report that there is a decreased expression of UGT2B7 mRNA in both ER+ and ER− breast cancer tissues . However, the UGT2B7 TTGA haplotype was significantly associated with PR status in patients with breast cancer in this study.…”

“…29 However, the present study indicates that there is no association between UGT2B7 polymorphisms and ER status in breast cancer, consistent with the report that there is a decreased expression of UGT2B7 mRNA in both ER+ and ER− breast cancer tissues. 24 However, the UGT2B7 TTGA haplotype was significantly associated with PR status in patients with breast cancer in this study. It has been suggested that 6α-and 21-hydroxyprogesterone could be used as selective "probes" for human liver microsomal UGT2B7 activity, 33 which may explain the relationship between UGT2B7 polymorphisms and the expression of the PR in breast cancer.…”

“…Scherer et al observed an association between a UGT2B15 polymorphism and increased risk of colorectal cancer. Vidal et al reported African American men who carry the wild‐type functional UGT2B15 gene have an elevated risk of prostate cancer. Second, oestrogens (eg, estradiol and estriol) and catecholestrogens (eg, 16‐OH‐estrone) are substrates of UGT2B7 .…”

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

“…This is supported with controversial association of UGT2B17 with testosterone‐related pathophysiological conditions, prostate cancer 44. That is, whereas some studies support association of UGT2B17 gene deletion with prostate cancer,18 a recent large study failed to confirm the same,40 perhaps due to high variability in UGT2B17 17, 45. Particularly, we recently demonstrated that UGT2B17 is associated with single nucleotide polymorphism (rs7436962, rs9996186, rs28374627, and rs4860305), age, and gender besides gene deletion 36…”

Identification of Novel SNPs Associated with Risk and Prognosis in Patients with Castration-Resistant Prostate Cancer

“…An SNP in UGT2B15, rs4148269, was associated with PCa risk due to variable expression of a cis-regulatory element resulting in differential expression of the steroid hormone glucuronidase [17,18].…”