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

BACKGROUND: We 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 evalua...

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Autores principales: Vidal, Adriana C, Tucker, Cocoa, Schildkraut, Joellen M, Richardson, Ricardo M, McPhail, Megan, Freedland, Stephen J, Hoyo, Cathrine, Grant, Delores J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924347/
https://www.ncbi.nlm.nih.gov/pubmed/24267955
http://dx.doi.org/10.1186/1471-2407-13-556
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author Vidal, Adriana C
Tucker, Cocoa
Schildkraut, Joellen M
Richardson, Ricardo M
McPhail, Megan
Freedland, Stephen J
Hoyo, Cathrine
Grant, Delores J
author_facet Vidal, Adriana C
Tucker, Cocoa
Schildkraut, Joellen M
Richardson, Ricardo M
McPhail, Megan
Freedland, Stephen J
Hoyo, Cathrine
Grant, Delores J
author_sort Vidal, Adriana C
collection PubMed
description BACKGROUND: We 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. METHODS: Fifteen 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. RESULTS: After 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. CONCLUSIONS: Although 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.
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spelling pubmed-39243472014-02-15 Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study Vidal, Adriana C Tucker, Cocoa Schildkraut, Joellen M Richardson, Ricardo M McPhail, Megan Freedland, Stephen J Hoyo, Cathrine Grant, Delores J BMC Cancer Research Article BACKGROUND: We 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. METHODS: Fifteen 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. RESULTS: After 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. CONCLUSIONS: Although 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. BioMed Central 2013-11-22 /pmc/articles/PMC3924347/ /pubmed/24267955 http://dx.doi.org/10.1186/1471-2407-13-556 Text en Copyright © 2013 Vidal et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Vidal, Adriana C
Tucker, Cocoa
Schildkraut, Joellen M
Richardson, Ricardo M
McPhail, Megan
Freedland, Stephen J
Hoyo, Cathrine
Grant, Delores J
Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study
title Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study
title_full Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study
title_fullStr Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study
title_full_unstemmed Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study
title_short Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study
title_sort novel associations of udp-glucuronosyltransferase 2b gene variants with prostate cancer risk in a multiethnic study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924347/
https://www.ncbi.nlm.nih.gov/pubmed/24267955
http://dx.doi.org/10.1186/1471-2407-13-556
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