title: Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study.
abstract: Mitochondria are eukaryotic organelles responsible for energy production. Mitochondrial DNA (mtDNA) lack introns and protective histones, have limited DNA repair capacity and compensate for damage by increasing the number of mtDNA copies. As a consequence, mitochondria are more susceptible to reactive oxygen species, an important determinant of cancer risk, and it is hypothesized that increased mtDNA copy number may be associated with carcinogenesis. We assessed the association of mtDNA copy number and lung cancer risk in 227 prospectively collected cases and 227 matched controls from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age at randomization, smoking years and number of cigarettes smoked per day. There was suggestion of a dose-dependent relationship between mtDNA copy number and subsequent risk of lung cancer, with a prominent effect observed in the highest mtDNA copy number quartile [ORs (95% CI) by quartile: 1.0 (reference), 1.3 (0.7-2.5), 1.1 (0.6-2.2) and 2.4 (1.1-5.1); P(trend) = 0.008]. This is the first report, to the best of our knowledge, to suggest that mtDNA copy number may be positively associated with subsequent risk of lung cancer in a prospective cohort study; however, replication is needed in other studies and populations.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 8118, MCS 7240, Bethesda, MD 20892-7240, USA. hosgoodd@mail.nih.gov
authors.forename: H Dean
authors.initials: HD
authors.lastname: Hosgood
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Bonner
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Unhee
authors.initials: U
authors.lastname: Lim
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Wen-ling
authors.initials: WL
authors.lastname: Cheng
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D000368:Aged; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D012306:Risk; D012907:Smoking / Q000009:adverse effects
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species