Association of leukocyte mitochondrial DNA copy number with colorectal cancer risk: Results from the Shanghai Women's Health Study.

Abstract

Mitochondria play an important role in cellular energy metabolism, free radical production, and apoptosis, and thus may be involved in cancer development. We evaluated mitochondrial DNA (mtDNA) copy number in peripheral leukocytes in relation to colorectal cancer risk in a case-control study of 444 colorectal cancer cases and 1,423 controls nested in the Shanghai Women's Health Study, a population-based, prospective cohort study. Relative mtDNA copy number was determined by a quantitative real-time PCR assay using peripheral leukocyte DNA samples collected at the time of study enrollment, before cancer diagnosis. We found that baseline mtDNA copy number was lower among women who subsequently developed colorectal cancer [geometric mean, 0.277; 95% confidence interval (CI), 0.269-0.285] than among women who remained cancer-free (geometric mean, 0.288; 95% CI, 0.284-0.293; P = 0.0153). Multivariate adjusted ORs were 1.26 (95% CI, 0.93-1.70) and 1.44 (95% CI, 1.06-1.94) for the middle and lower tertiles of mtDNA copy number, respectively, compared with the upper tertile (highest mtDNA copy number; Ptrend = 0.0204). The association varied little by the interval between blood collection and cancer diagnosis. Our data suggest that mtDNA copy number measured in peripheral leukocytes may be a potential biomarker useful for colorectal cancer risk assessment. If confirmed, mtDNA copy number measured in peripheral leukocytes may be a biomarker useful for colorectal cancer risk assessment.