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Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk

BACKGROUND: Mitochondria are the site of oxidative phosphorylation, a process which generates reactive oxygen species (ROS). Elevated ROS levels can lead to oxidative stress, a cellular state implicated in carcinogenesis. It is hypothesized that alternations in mitochondrial (MT) DNA, including heri...

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Autores principales: Earp, Madalene A, Brooks-Wilson, Angela, Cook, Linda, Le, Nhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854008/
https://www.ncbi.nlm.nih.gov/pubmed/24148579
http://dx.doi.org/10.1186/1756-0500-6-425
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author Earp, Madalene A
Brooks-Wilson, Angela
Cook, Linda
Le, Nhu
author_facet Earp, Madalene A
Brooks-Wilson, Angela
Cook, Linda
Le, Nhu
author_sort Earp, Madalene A
collection PubMed
description BACKGROUND: Mitochondria are the site of oxidative phosphorylation, a process which generates reactive oxygen species (ROS). Elevated ROS levels can lead to oxidative stress, a cellular state implicated in carcinogenesis. It is hypothesized that alternations in mitochondrial (MT) DNA, including heritable MT single nucleotide polymorphisms (MT-SNPs), have the potential to change the capacity of MT function, leading to increased oxidative stress and cancer risk. We investigated if common MT-SNPs and/or haplogroups and are associated with invasive serous ovarian cancer (OvCa) risk. METHODS: A panel of 64 MT-SNPs designed to tag all common variation in the European MT genome (minor allele frequency (MAF) >1%, r^2 >0.8) was genotyped in study participants of European descent using the Sequenom MassARRAY iPlex Gold® system (Sequenom Inc, CA, USA). Invasive serous OvCa cases (n = 405) and frequency age-matched controls (n = 445) were drawn from a population-based case-control study of OvCa in western Canada. Binary logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (C.I.) for carriage of the minor versus major allele by case-control status. MitoTool was used to test the relationship between European haplogroup status and case-control status using Fisher’s exact test. RESULTS: The most significant disease-SNP association was for rs2857285, a synonymous MT-SNP in ND4 (OR = 4.84, 95% CI: 1.03–22.68, P = 0.045). After adjustment for multiple testing using a Bonferroni correction of the Type 1 error this MT-SNP was not significant. No other MT-SNP had a P-value < 0.05. European haplogroup status was not associated with case status. Most MT-SNPs (73%) genotyped had a MAF <5%. CONCLUSION: Common European MT-SNPs (MAF > 5%) and haplogroups were not associated with invasive serous OvCa risk in this study; however, most European MT-SNPs have a low MAF (<5%), which we were underpowered to adequately assess. Larger studies are needed to clarify the role of low MAF MT-SNPs (MAF < 5%) in invasive serous OvCa risk.
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spelling pubmed-38540082013-12-07 Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk Earp, Madalene A Brooks-Wilson, Angela Cook, Linda Le, Nhu BMC Res Notes Research Article BACKGROUND: Mitochondria are the site of oxidative phosphorylation, a process which generates reactive oxygen species (ROS). Elevated ROS levels can lead to oxidative stress, a cellular state implicated in carcinogenesis. It is hypothesized that alternations in mitochondrial (MT) DNA, including heritable MT single nucleotide polymorphisms (MT-SNPs), have the potential to change the capacity of MT function, leading to increased oxidative stress and cancer risk. We investigated if common MT-SNPs and/or haplogroups and are associated with invasive serous ovarian cancer (OvCa) risk. METHODS: A panel of 64 MT-SNPs designed to tag all common variation in the European MT genome (minor allele frequency (MAF) >1%, r^2 >0.8) was genotyped in study participants of European descent using the Sequenom MassARRAY iPlex Gold® system (Sequenom Inc, CA, USA). Invasive serous OvCa cases (n = 405) and frequency age-matched controls (n = 445) were drawn from a population-based case-control study of OvCa in western Canada. Binary logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (C.I.) for carriage of the minor versus major allele by case-control status. MitoTool was used to test the relationship between European haplogroup status and case-control status using Fisher’s exact test. RESULTS: The most significant disease-SNP association was for rs2857285, a synonymous MT-SNP in ND4 (OR = 4.84, 95% CI: 1.03–22.68, P = 0.045). After adjustment for multiple testing using a Bonferroni correction of the Type 1 error this MT-SNP was not significant. No other MT-SNP had a P-value < 0.05. European haplogroup status was not associated with case status. Most MT-SNPs (73%) genotyped had a MAF <5%. CONCLUSION: Common European MT-SNPs (MAF > 5%) and haplogroups were not associated with invasive serous OvCa risk in this study; however, most European MT-SNPs have a low MAF (<5%), which we were underpowered to adequately assess. Larger studies are needed to clarify the role of low MAF MT-SNPs (MAF < 5%) in invasive serous OvCa risk. BioMed Central 2013-10-22 /pmc/articles/PMC3854008/ /pubmed/24148579 http://dx.doi.org/10.1186/1756-0500-6-425 Text en Copyright © 2013 Earp 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
Earp, Madalene A
Brooks-Wilson, Angela
Cook, Linda
Le, Nhu
Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk
title Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk
title_full Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk
title_fullStr Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk
title_full_unstemmed Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk
title_short Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk
title_sort inherited common variants in mitochondrial dna and invasive serous epithelial ovarian cancer risk
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854008/
https://www.ncbi.nlm.nih.gov/pubmed/24148579
http://dx.doi.org/10.1186/1756-0500-6-425
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