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

Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2357-65. doi: 10.1158/1055-9965.EPI-14-0297. Epub 2014 Aug 19.

Abstract

Background: Mitochondria play an important role in cellular energy metabolism, free radical production, and apoptosis, and thus may be involved in cancer development.

Methods: 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.

Results: 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.

Conclusions: Our data suggest that mtDNA copy number measured in peripheral leukocytes may be a potential biomarker useful for colorectal cancer risk assessment.

Impact: If confirmed, mtDNA copy number measured in peripheral leukocytes may be a biomarker useful for colorectal cancer risk assessment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • China / epidemiology
  • Colonic Neoplasms / epidemiology
  • Colonic Neoplasms / genetics*
  • DNA Copy Number Variations*
  • DNA, Mitochondrial*
  • Female
  • Humans
  • Leukocytes*
  • Middle Aged
  • Prospective Studies
  • Rectal Neoplasms / epidemiology
  • Rectal Neoplasms / genetics*
  • Risk Factors

Substances

  • Biomarkers, Tumor
  • DNA, Mitochondrial