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Carcinogenesis. 2015 Nov;36(11):1307-13. doi: 10.1093/carcin/bgv130. Epub 2015 Sep 10.

Peripheral blood mitochondrial DNA copy number, length heteroplasmy and breast cancer risk: a replication study.

Author information

1
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Houston, TX 77030, USA.
2
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Houston, TX 77030, USA hzhao2@mdanderson.org.

Abstract

Oxidative stress has consistently been linked to breast carcinogenesis, and mitochondria play a significant role in regulating reactive oxygen species generation. In our previous study, we found that increased levels of mitochondrial DNA (mtDNA) copy number and the presence of mitochondrial length heteroplasmies in the hypervariable (HV) regions 1 and 2 (HV1 and HV2) in peripheral blood are associated with increased risk of breast cancer. In current study with 1000 breast cancer cases and 1000 healthy controls, we intended to replicate our previous findings. Overall, levels of mtDNA copy number were significantly higher in breast cancer cases than healthy controls (mean: 1.17 versus 0.94, P < 0.001). In the multivariate linear regression analysis, increased mtDNA copy number levels were associated with a 1.32-fold increased risk of breast cancer [adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.15-1.67]. Breast cancer cases were more likely to have HV1 and HV2 region length heteroplasmies than healthy controls (P < 0.001, respectively). The existence of HV1 and HV2 length heteroplasmies was associated with 2.01- and 1.63-folds increased risk of breast cancer (for HV1: OR = 2.01, 95% CI = 1.66-2.42; for HV2: OR = 1.63, 95% CI = 1.34-1.92). Additionally, joint effects among mtDNA copy number, HV1 and HV2 length heteroplasmies were observed. Our results are consistent with our previous findings and further support the roles of mtDNA copy number and mtDNA length heteroplasmies that may play in the development of breast cancer.

PMID:
26363030
PMCID:
PMC4751248
DOI:
10.1093/carcin/bgv130
[Indexed for MEDLINE]
Free PMC Article

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