Pooled Analysis of Mitochondrial DNA Copy Number and Lung Cancer Risk in Three Prospective Studies

Background: We previously reported that higher levels of mitochondrial DNA copy number (mtDNA CN) were associated with lung cancer risk among male heavy smokers (i.e., >= 20 cigarettes per day) in the Alpha-Tocopherol Beta-Carotene (ATBC) study. Here, we present two additional prospective investigations nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and the Shanghai Women's Health Study (SWHS), and pooled with previously published data from ATBC. Materials: All DNA were extracted from peripheral whole blood samples using the phenol-chloroform method, and mtDNA CN was assayed by fluorescence-based qPCR. Multivariate unconditional logistic regression models were used to estimate ORs and 95% confidence intervals for the association of mtDNA CN and lung cancer risk. Results: Overall, mtDNA CN was not associated with lung cancer risk in the PLCO, SWHS, or pooled populations (all P trends > 0.42, P heterogeneity = 0.0001), and mtDNA CN was inversely associated with lung cancer risk among male smokers in PLCO, the opposite direction observed in ATBC. In addition, the mtDNA CN association observed among male heavy smokers in ATBC was the opposite direction in PLCO. Conclusions: mtDNA CN was not consistently associated with lung cancer risk across three prospective study populations from Europe, Asia, and the United States. Impact: This pooled study suggests no consistent association between prediagnostic mtDNA CN levels and lung cancer risk across several populations. (C) 2014 AACR.