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

Jonathan N. Hofmann, Howard D. Hosgood, Chin San Liu, Wong Ho Chow, Brian Shuch, Wen Ling Cheng, Ta Tsung Lin, Lee E. Moore, Qing Lan, Nathaniel Rothman, Mark P. Purdue

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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; Ptrend = 0.002) and among cases diagnosed ≥6 years after blood collection (OR = 2.6, 95% CI = 1.4-5.0; Ptrend = 0.003). These findings did not differ significantly by sex, body mass index, history of hypertension or smoking status (Pinteraction ≥ 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.

Original languageEnglish (US)
Pages (from-to)1028-1031
Number of pages4
JournalCarcinogenesis
Volume35
Issue number5
DOIs
StatePublished - 2014

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Mitochondrial DNA
Early Detection of Cancer
Renal Cell Carcinoma
Ovarian Neoplasms
Case-Control Studies
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Leukocytes
Odds Ratio
Confidence Intervals
DNA Damage
Body Mass Index
Fluorescence
Logistic Models
Smoking
Hypertension
Polymerase Chain Reaction
Mutation

ASJC Scopus subject areas

  • Cancer Research

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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. / Hofmann, Jonathan N.; Hosgood, Howard D.; Liu, Chin San; Chow, Wong Ho; Shuch, Brian; Cheng, Wen Ling; Lin, Ta Tsung; Moore, Lee E.; Lan, Qing; Rothman, Nathaniel; Purdue, Mark P.

In: Carcinogenesis, Vol. 35, No. 5, 2014, p. 1028-1031.

Research output: Contribution to journalArticle

Hofmann, Jonathan N. ; Hosgood, Howard D. ; Liu, Chin San ; Chow, Wong Ho ; Shuch, Brian ; Cheng, Wen Ling ; Lin, Ta Tsung ; Moore, Lee E. ; Lan, Qing ; Rothman, Nathaniel ; Purdue, Mark P. / 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. In: Carcinogenesis. 2014 ; Vol. 35, No. 5. pp. 1028-1031.
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