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Int J Mol Epidemiol Genet 2010;1(3):184-192.

Original Article
Length heteroplasmies in human mitochondrial DNA control regions and
breast cancer risk

Hua Zhao, Jie Shen, Leonard Medico, Mary Platek, Christine B. Ambrosone

Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

Received March 2, 2010, accepted March 31, 2010, available online April 5, 2010

Abstract: It has been proposed that the presence of heteroplasmy in the hypervariable (HV) regions of the mitochondrial DNA
(mtDNA) may be an indicator of mitochondrial genome instability, mtDNA dysfunction, and, thus, may be associated with
increased cancer risk. However, whether heteroplasmy in the HV regions of mtDNA could be a risk predictor of oxidative
stress-related human cancers, such as breast cancer, remains to be determined. To explore the role of heteroplasmy in the HV
regions of mtDNA in breast cancer etiology, we analyzed heteroplasmy in the HV regions of mtDNA in whole blood from 103
patients with breast cancer and 103 matched control subjects. Both cases and controls displayed heteroplasmies in both of
the HV1 and HV2 regions. Closer examination of the prevalence of length heteroplasmy indicated that the prevalence of
heteroplasmies in both of the HV1 and HV2 regions was much higher in the cases than in the controls (HV1: 68% vs 49%,
P=0.007; HV2: 46% vs 25%, P=0.002). The presence of length heteroplasmies in both of the HV1 and HV2 regions was
associated with 2.18- and 2.49-folds increased risk of breast cancer, respectively, (HV1: OR=2.18, 95% CI: 1.19 - 4.00; HV2:
OR=2.49, 95% CI: 1.32 - 4.69). Interestingly, we observed that the controls with length heteroplasmies in both HV1 and HV2
had statistically significantly lower copy number of mtDNA than the ones without heteroplasmies. These results suggest that
the length heteroplasmy in the HV regions of mtDNA could be associated with a risk of breast cancer, perhaps through
affecting the copy number of mtDNA. (IJMEG1003001).

Key words: Mitochondrial DNA, length heteroplasmies, copy number, breast cancer

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Address all correspondence to:
Hua Zhao, PhD,
Department of Cancer Prevention and Control
Roswell Park Cancer Institute, Elm and Carlton Streets
Basic Science 704, Buffalo, NY 14263.
Tel: 716-845-3103; Fax: 716 - 8 4 5 -1356
E-mail:
hua.zhao@roswellpark.org.