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

被引：13
作者：
Earp M.A. [1 ]
Brooks-Wilson A. [1 ,2 ,7 ]
Cook L. [3 ,4 ,5 ]
Le N. [6 ]
机构：
[1] Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC
[2] Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC
[3] Department of Internal Medicine, NM Health Sciences Center, University of New Mexico, Albuquerque
[4] Department of Population Health Research, Division of Cancer Care, Alberta Health Services, Calgary, AB T2C 3S3
[5] Department of Community Health Sciences, Faculty of Medicine, University of Calgary, Calgary, AB T2N 4N2
[6] Cancer Control Research, BC Cancer Agency, Vancouver
[7] Genome Sciences Centre, BC Cancer Research Centre, Vancouver BC V5Z 1L3
来源：
BMC Research Notes | / 6卷 / 1期
基金：
加拿大健康研究院;
关键词：
Epithelial ovarian cancer; European; Haplogroup; Heritable risk; Mitochondrial DNA; Serous ovarian cancer; Single nucleotide polymorphism;
D O I：
10.1186/1756-0500-6-425
中图分类号：
学科分类号：
摘要：
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%, r2 >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. © 2013 Earp et al.; licensee BioMed Central Ltd.
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