title: A nested case-control study of leukocyte mitochondrial DNA copy number and renal cell carcinoma in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.
abstract: Mitochondrial DNA (mtDNA) is vulnerable to mutations, and the number of copies of mtDNA per cell may increase to compensate for DNA damage. Case-control studies have reported associations between altered mtDNA copy number and risk of renal cell carcinoma (RCC); however, this association has not been investigated prospectively. We conducted a nested case-control study (252 cases and 504 controls) of RCC risk in relation to pre-diagnostic leukocyte mtDNA copy number in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. mtDNA copy number was measured in triplicate using a fluorescence-based quantitative PCR assay; samples from 22 cases and 36 controls could not be assayed, leaving 230 cases and 468 controls for analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. High mtDNA copy number was associated with an increased risk of RCC, both overall (highest quartile versus lowest: OR = 2.0, 95% CI = 1.2-3.2; P trend = 0.002) and among cases diagnosed ≥6 years after blood collection (OR = 2.6, 95% CI = 1.4-5.0; P trend = 0.003). These findings did not differ significantly by sex, body mass index, history of hypertension or smoking status (P interaction ≥ 0.3). Results of this study suggest that high pre-diagnostic leukocyte mtDNA copy number, a suspected marker of oxidative DNA damage and mitochondrial dysfunction, is associated with increased future RCC risk.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Hofmann
authors.forename: H Dean
authors.initials: HD
authors.lastname: Hosgood
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Brian
authors.initials: B
authors.lastname: Shuch
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Cheng
authors.forename: Ta-Tsung
authors.initials: TT
authors.lastname: Lin
authors.forename: Lee E
authors.initials: LE
authors.lastname: Moore
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors
chemical_list: D004272:DNA, Mitochondrial