Association Between Mitochondrial DNA Content in Leukocytes and Colorectal Cancer Risk

BACKGROUND: Compelling epidemiological evidence indicated that alterations of mitochondria! DNA (mtDNA), including mutations and abnormal content of mtDNA, were implicated in the tumorigenesis of several malignancies in a tumor-specific manner, such as lung cancer, breast cancer, and non-Hodgkin lymphoma. This study was undertaken to investigate whether mtDNA content in peripheral blood lymphocytes (PBLs) could be used as a risk predictor for colorectal cancer (CRC). METHODS: The mtDNA content was measured by using quantitative real-time polymerase chain reaction in PBLs from 320 CRC patients and 320 matched controls. RESULTS: The authors found that CRC patients exhibited statistically significantly higher mtDNA content than matched controls (median, 1.03 vs.86; P < .001). They further assessed the association between mtDNA content and CRC risk using multivariate logistic regression. By using the median value in controls as the cutoff point, they found that, compared with low mtDNA content, high mtDNA content was associated with a significantly increased CRC risk (adjusted odds ratio, 2.03; 95% confidence interval, 1.41-2.81). In a trend analysis, they found a statistically significant dose-response relationship between higher mtDNA content and increased CRC risk (P for trend <.001). Stratified analysis showed that the association between mtDNA content and CRC risk was not modulated by major host characteristics. CONCLUSIONS: These findings provide the first epidemiological evidence linking the high mtDNA content in PBLs to elevated CRC risk. Cancer 2011;117:3148-55. (C) 2011 American Cancer Society.