Basic scienceAssociation Between Polymorphisms in HSD3B1 and UGT2B17 and Prostate Cancer Risk
Section snippets
Study Populations and Sample Processing
The appropriate institutional review board approvals were obtained for the study protocol at each institution. All study subjects provided written informed consent. A total of 356 incident patients with primary adenocarcinoma of the prostate (331 whites, 24 African Americans, and 1 other) were recruited from 2002 to 2005 at the H. Lee Moffitt Cancer Center (Tampa, Fla) and James A. Haley Veterans Affairs Hospital (Tampa, FL). Ninety-five percent of the case subjects who were asked to
Results
Table 1 provides descriptive characteristics of the patients and controls. Despite the frequency matching by age, the patients tended to be older than the controls (P <0.0001). The median age was 65 years at diagnosis for the patients and 60 years at interview for the controls. More men with prostate cancer (24%) than without (8%) reported having a first-degree family member with prostate cancer (P <0.0001). As expected, the prostate-specific antigen levels of most patients were greater than 4
Comment
In the present study, we observed that polymorphisms in HSD3B1 and UGT2B17 were associated with prostate cancer risk. These data are consistent with the hypothesis that these enzymes may play a role in the degradation of DHT21 and that an excessive amount of DHT may be associated with carcinogenesis in prostatic tissue.22
The HSD3B1 codon 367 polymorphism may have an impact on HSD3B1 enzyme activity. This amino acid change from asparagine to threonine creates a new potential protein kinase C
Conclusions
Our data have suggested a potential joint effect between the HSD3B1 codon 367 and UGT2B17 deletion polymorphisms in relation to the risk of prostate cancer. These results warrant a larger study in the context of prostate cancer susceptibility, and basic research on the function of this enzyme, allelic variants, and other androgen-metabolizing enzymes.
Acknowledgment
To the Molecular Biology Core facility at H. Lee Moffitt Cancer Center for excellent technical assistance.
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2018, Comprehensive Toxicology: Third EditionGenetic variations in UGT2B28, UGT2B17, UGT2B15 genes and the risk of prostate cancer: A case-control study
2017, GeneCitation Excerpt :Previous findings revealed that the urine testosterone concentrations is different between subjects stratified by UGT2B17 CNV genotypes, where lower mean concentration was observed in people with two deleted UGT2B17 alleles in comparison to those who carry one copy of the gene (Jakobsson et al., 2006; Juul et al., 2009). In overall, mentioned UGT2B variants have been evaluated in relation to prostate cancer risk, with inconsistent findings (Gsur et al., 2002; Hajdinjak and Zagradišnik, 2004; MacLeod et al., 2000; Park et al., 2004; Park et al., 2007; Setlur et al., 2010; Park et al., 2006; Olsson et al., 2008; Karypidis et al., 2008). For example, some studies have shown that null genotype of UGT2B17 gene is linked to increased risk of PC in African-American and Caucasian races (Park et al., 2006; Karypidis et al., 2008).
UDP-glucuronosyltransferase 2B17 genotype and the risk of lung cancer among Austrian Caucasians
2013, Cancer EpidemiologyCitation Excerpt :Thus, ranges of UGT2B17 genotypes were 41–54% and 33–64% (+/+), 33–48% and 32–52% (+/−), and 4–19% and 3–27% (−/−) in cancer patients and healthy individuals, respectively, of Caucasian descent from different geographic regions [8–14,16,21–24]. This high variability of genotype frequencies may partly explain the ambiguous data regarding the risks for individuals to develop prostate cancer [9–15], although Cai and colleagues demonstrated in a recent meta-analysis a consistent and high prostate cancer risk for men carrying the null genotype when compared to men-based controls but not in studies using population as controls [25]. Considering the heterogeneity of genotype frequencies, one limitation of our study is sample size.
Polymorphisms in androgen signaling pathway predisposing to prostate cancer
2012, Molecular and Cellular EndocrinologyCitation Excerpt :In a case-control study of 356 PCa cases and 363 age-matched controls the UGT2B17 null polymorphism was associated with overall PCa risk. Risk for PCa associated with UGT2B17 null polymorphisms was further elevated among individuals with HSD3B1 variant (Park et al., 2007). In another study by Karypidis et al. (2008) a deletion polymorphism of UGT2B17 was found to be significantly associated with increased risk of PCa but no association was detected between the UTG2B17 del allele and metastatic disease or high-grade tumor differentiation.