Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case-Control to a Meta-Analysis of 20,098 Subjects

Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case-Control to a Meta-Analysis of 20,098 Subjects

Lifetime exposure to estrogen is a factor that plays an important role in the pathogenesis and progression of breast cancer. Genetic variants in genes of the biosynthesis and metabolism of estrogen have been associated with breast cancer risk. Among them, the CYP19 gene encodes for aromatase, the en...

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Main Authors: Pineda, Begoña, García-Pérez, Miguel Ángel, Cano, Antonio, Lluch, Ana, Eroles, Pilar
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547044/
id pubmed-3547044
recordtype oai_dc
spelling pubmed-35470442013-01-22 Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case-Control to a Meta-Analysis of 20,098 Subjects Pineda, Begoña García-Pérez, Miguel Ángel Cano, Antonio Lluch, Ana Eroles, Pilar Research Article Lifetime exposure to estrogen is a factor that plays an important role in the pathogenesis and progression of breast cancer. Genetic variants in genes of the biosynthesis and metabolism of estrogen have been associated with breast cancer risk. Among them, the CYP19 gene encodes for aromatase, the enzyme that catalyzes the conversion of androgens to estrogens. The rs10046 polymorphism on the CYP19 gene has been related to levels of circulating estradiol and to the estradiol/testosterone ratio. To date, epidemiological studies of rs10046 have been performed in different populations with contradictory results. In the present study, we have conducted a case-control analysis (522 cases and 1221 controls) in a Spanish population. Furthermore, we have performed a meta-analysis including 20,098 subjects (7,998 cases and 12,100 controls) to summarize the data available for rs10046 and breast cancer risk. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association. The results of our case-control study show an association between the carriers of at least one C allele (dominant model) and breast cancer risk (OR = 1.29, 95% CI 1.01–1.66, p-value = 0.038). The meta-analysis shows no significant association with breast cancer risk in any of the genetic models tested. The analysis by ethnic subgroups also failed to produce associations. The evaluation of heterogeneity, influence analysis, and publication bias confirms the reliability of the analysis. We can conclude that the rs10046 polymorphism on CYP19 by itself does not constitute breast cancer risk. We cannot, however, reject the possibility that it could contribute (interact), together with other genetic variants, to modify the circulating levels of estradiol. Public Library of Science 2013-01-16 /pmc/articles/PMC3547044/ /pubmed/23342035 http://dx.doi.org/10.1371/journal.pone.0053902 Text en © 2013 Pineda et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Pineda, Begoña
García-Pérez, Miguel Ángel
Cano, Antonio
Lluch, Ana
Eroles, Pilar
spellingShingle Pineda, Begoña
García-Pérez, Miguel Ángel
Cano, Antonio
Lluch, Ana
Eroles, Pilar
Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case-Control to a Meta-Analysis of 20,098 Subjects
author_facet Pineda, Begoña
García-Pérez, Miguel Ángel
Cano, Antonio
Lluch, Ana
Eroles, Pilar
author_sort Pineda, Begoña
title Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case-Control to a Meta-Analysis of 20,098 Subjects
title_short Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case-Control to a Meta-Analysis of 20,098 Subjects
title_full Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case-Control to a Meta-Analysis of 20,098 Subjects
title_fullStr Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case-Control to a Meta-Analysis of 20,098 Subjects
title_full_unstemmed Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case-Control to a Meta-Analysis of 20,098 Subjects
title_sort associations between aromatase cyp19 rs10046 polymorphism and breast cancer risk: from a case-control to a meta-analysis of 20,098 subjects
description Lifetime exposure to estrogen is a factor that plays an important role in the pathogenesis and progression of breast cancer. Genetic variants in genes of the biosynthesis and metabolism of estrogen have been associated with breast cancer risk. Among them, the CYP19 gene encodes for aromatase, the enzyme that catalyzes the conversion of androgens to estrogens. The rs10046 polymorphism on the CYP19 gene has been related to levels of circulating estradiol and to the estradiol/testosterone ratio. To date, epidemiological studies of rs10046 have been performed in different populations with contradictory results. In the present study, we have conducted a case-control analysis (522 cases and 1221 controls) in a Spanish population. Furthermore, we have performed a meta-analysis including 20,098 subjects (7,998 cases and 12,100 controls) to summarize the data available for rs10046 and breast cancer risk. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association. The results of our case-control study show an association between the carriers of at least one C allele (dominant model) and breast cancer risk (OR = 1.29, 95% CI 1.01–1.66, p-value = 0.038). The meta-analysis shows no significant association with breast cancer risk in any of the genetic models tested. The analysis by ethnic subgroups also failed to produce associations. The evaluation of heterogeneity, influence analysis, and publication bias confirms the reliability of the analysis. We can conclude that the rs10046 polymorphism on CYP19 by itself does not constitute breast cancer risk. We cannot, however, reject the possibility that it could contribute (interact), together with other genetic variants, to modify the circulating levels of estradiol.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547044/
_version_ 1611947659230183424

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