Association Between Polymorphisms in HSD3B1 and UGT2B17 and Prostate Cancer Risk

Park, Jong Y.; Tanner, Jean-Paul; Sellers, Thomas A.; Huang, Yifan; Stevens, Colleen K.; Dossett, Nicole; Shankar, Ravi; Zachariah, Babu; Heysek, Randy V.; Pow‐Sang, Julio M.

doi:10.1016/j.urology.2007.03.001

Cited by 43 publications

(39 citation statements)

References 19 publications

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“…We showed no association with prostate cancer risk consistent with some previous reports (Gallagher et al, 2007;Olsson et al, 2008;Setlur et al, 2010). However, other studies reported that individuals homozygous for the UGT2B17 deletion were at increased risk for prostate cancer, while a report showed that only carriers of the UGT2B17 deletion had increased risk (Park et al, 2006(Park et al, , 2007Karypidis et al, 2007). These differences across studies could be the result of interindividual variability in the UGT2B gene expression and haplotype structure of the UGT2B genes within each study population (Izukawa et al, 2009;Menard et al, 2009).…”

Section: Ugt2b Variants: Aag Levels and Prostate Cancer Risksupporting

confidence: 87%

“…The association of the UGT2B15 D85Y polymorphism with prostate cancer has been examined with conflicting results (MacLeod et al, 2000;Gsur et al, 2002;Hajdinjak and Zagradisnik, 2004;Park et al, 2004;Cunningham et al, 2007). Similarly, numerous studies have explored the association of the UGT2B17 CNV and prostate cancer also with inconsistent conclusions (Park et al, 2006(Park et al, , 2007Gallagher et al, 2007;Karypidis et al, 2007;Olsson et al, 2008;Setlur et al, 2010). Some of the inconsistencies in these findings could be explained by differences in the composition of the study participants.…”

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confidence: 99%

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Association of Uridine Diphosphate-Glucuronosyltransferase 2B Gene Variants with Serum Glucuronide Levels and Prostate Cancer Risk

Grant

Hoyo

Oliver

et al. 2013

Genetic Testing and Molecular Biomarkers

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Aims: Uridine diphosphate-glucuronosyltransferase 2B (UGT2B) enzymes conjugate testosterone metabolites to enable their excretion in humans. The functional significance of the UGT2B genetic variants has never been described in humans. We evaluated UGT2B variants in relation to plasma androstane-3a,17b-diol-glucuronide (AAG) levels and the prostate cancer risk. Results: AAG levels were measured in sera from 150 controls and compared to the polymorphisms of UGT2B17, UGT2B15, and UGT2B7. Genomic DNA from controls (301) and cases (148) was genotyped for the polymorphisms, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analyses. Having two copies of UGT2B17 was associated with higher AAG levels in controls among Whites ( p = 0.02), but not Blacks ( p = 0.82). Logistic regression models adjusting for age and race revealed that homozygosity for the G allele of the UGT2B15 D85Y polymorphism was directly associated with the prostate cancer risk (OR = 2.70, 95% CI = 1.28, 5.55). Conclusions: While the small sample size limits inference, our findings suggest that an association between the UGT2B17 copy number variant (CNV) and serum AAG levels in Whites, but unexpectedly not in Blacks. This novel observation suggests that genetic determinants of AAG levels in Blacks are unrelated to the UGT2B17 CNV. This study replicates the results that show an association of UGT215 D85Y with an increased prostate cancer risk.

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Section: Ugt2b Variants: Aag Levels and Prostate Cancer Risksupporting

confidence: 87%

mentioning

confidence: 99%

Association of Uridine Diphosphate-Glucuronosyltransferase 2B Gene Variants with Serum Glucuronide Levels and Prostate Cancer Risk

Grant

Hoyo

Oliver

et al. 2013

Genetic Testing and Molecular Biomarkers

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“…Therefore, at least in the early stages of PC, 3b-Adiol formation may shift the equilibrium versus a slowing down of progression and invasiveness of the tumor cells. This exciting hypothesis has strong support in clinical observations, demonstrating that genetic alteration of several enzymes involved in androgenic steroid metabolism is linked to hereditary and sporadic PC susceptibility (Chang et al 2002, Steckelbroeck et al 2004, Bauman et al 2006, Cunningham et al 2007, Neslund-Dudas et al 2007, Park et al 2007, Ross et al 2008, Beuten et al 2009, Mindnich & Penning 2009). It has been established that enzyme responsible for 3b-Adiol formation from the DHT in prostate is AKR1C1; in fact, AKR1C1:AKR1C2 (responsible for 3a-diol formation from the DHT) transcript ratio fells in PC; thus, the data here presented provide clear explanations of these observations, since the reduction of 3b-Adiol levels in favor of 3a-Adiol may be a risk factor for PC in these patients, because the 3b-Adiol 'protective' effect will obviously disappear.…”

Section: Discussionmentioning

confidence: 88%

Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol

Dondi

Piccolella²,

Biserni³

et al. 2010

Endocrine-Related Cancer

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Prostate cancer (PC) develops in response to an abnormal activation of androgen receptor induced by circulating androgens and, in its initial stages, is pharmacologically controlled by androgen blockade. However, androgen ablation therapy often allows androgen-independent PC development, generally characterized by increased invasiveness. We previously reported that 5a-androstane-3b,17b-diol (3b-Adiol) inhibits the migration of PC cell lines via the estrogen receptor b (ERb) activation. Here, by combining in vitro assays and in vivo imaging approaches, we analyzed the effects of 3b-Adiol on PC proliferation, migration, invasiveness, and metastasis in cultured cells and in xenografts using luciferase-labeled PC3 (PC3-Luc) cells. We found that 3b-Adiol not only inhibits PC3-Luc cell migratory properties, but also induces a broader anti-tumor phenotype by decreasing the proliferation rate, increasing cell adhesion, and reducing invasive capabilities in vitro. All these 3b-Adiol activities are mediated by ERb and cannot be reproduced by the physiological estrogen, 17b-estradiol, suggesting the existence of different pathways activated by the two ERb ligands in PC3-Luc cells. In vivo, continuous administration of 3b-Adiol reduces growth of established tumors and counteracts metastasis formation when PC3-Luc cells are engrafted s.c. in nude mice or are orthotopically injected into the prostate. Since 3b-Adiol has no androgenic activity, and cannot be converted to androgenic compounds, the effects here described entail a novel potential application of this agent against human PC.

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“…Previous study assessing the association between UGT2B17 deletion and the risk of prostate cancer reported inconclusive and inconsistent findings. Therefore, to get a reliable conclusion of the association of UGT2B17 status and prostate risk, we conducted the present meta-analysis of 6 independent studies including a total of 7027 subjects (3839 cases and 3190 controls) [23][24][25][26][27][28]. Overall, there was a significant association between UGT2B17 status and increased risk of prostate cancer (Figure 2).…”

Section: Discussionmentioning

confidence: 95%

“…To date, a number of molecular epidemiological studies have been conducted to evaluate the effect of the UGT2B17 deletion on risk of prostate cancer [23][24][25][26][27][28]. However, until now, those studies that investigated associations between the UGT2B17 status and prostate cancer risk have yielded inconsistent results.…”

Section: Introductionmentioning

confidence: 99%

UGT2B17 status and risk of prostate cancer: A meta-analysis

Kpoghomou¹,

Kalembo²,

Soatiana³

et al. 2013

OJPM

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Objective: Recent studies on the association between Uridine diphosphoglucuronosyl tranferases (UGT) 2B17 status and risk of prostate cancer (PCa) showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies. Methods: We searched published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI). According to our inclusion criteria, studies that observed the association between UGT2B17 status and PCa risk were included. The principal outcome measure was the adjusted odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with UGT2B17 status. Results: A total of 6 studies with 7029 subjects (3839 cases and 3190 controls) were eligible for inclusion in the meta-analysis. Overall, there was a significant association between UGT2B17 status and increased risk of prostate cancer (OR = 1.74, 95% CI 1.14 -2.64, P < 0.001). Similar results were found in the subgroup analyses by ethnicity and types of controls. Conclusion: This meta-analysis demonstrates that UGT2B17 status is associated with prostate cancer susceptibility, and it contributes to increased risk of prostate cancer.

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Association Between Polymorphisms in HSD3B1 and UGT2B17 and Prostate Cancer Risk

Cited by 43 publications

References 19 publications

Association of Uridine Diphosphate-Glucuronosyltransferase 2B Gene Variants with Serum Glucuronide Levels and Prostate Cancer Risk

Association of Uridine Diphosphate-Glucuronosyltransferase 2B Gene Variants with Serum Glucuronide Levels and Prostate Cancer Risk

Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol

UGT2B17 status and risk of prostate cancer: A meta-analysis

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