Abstract 4320: Mitochondrial DNA copy number in peripheral blood and the risk of clear-cell renal cell carcinoma: Effect of age, gender, smoking, and history of hypertension
Authors: Wang Xin , Melkonian Stephanie , Gu Jian , Chang David , Tannir Nizar , Wood Christopher , Wu Xifeng 
Published: May 2015

Mitochondria are the primary source of cellular energy. Mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes (PBLs) has high genetic heritability and inter-individual variation of mtDNA copy number in PBLs has been associated with the risk of several human cancers. In this study, we investigated into the link between mtDNA and clear-cell renal cell carcinoma (ccRCC) in a large population-based case control study. We measured relative mtDNA copy number in PBLs from 616 Caucasian ccRCC cases and 603 controls frequency-matched on age, gender, and ethnicity. In the analyses of controls only, there was a significant inverse correlation between age and mtDNA copy number (P=0.001); men had significantly lower mtDNA copy number than women (P&lt;0.001); and both smoking and hypertension had a negative effect on mtDNA copy number (P=0.03 and 0.04, respectively). We found a significantly lower mtDNA copy number in cases compared to controls (mean±SD: 1.16±0.37 versus 1.21±0.39, P=0.04). Dichotomized at the median level of mtDNA copy number in controls, individuals with lower mtDNA copy number were at an increased risk of ccRCC (OR=1.20, 95% CI: 0.96-1.51, P=0.11) adjusting for age, gender, smoking status, BMI, and history of hypertension in a multivariate logistic regression analysis. In stratified analyses, the association between lower mtDNA copy number and increased ccRCC risks reached statistical significance in younger aged (age&lt;60) individuals (OR=1.56, 95% CI: 1.12-2.15, P=0.01), women (OR=1.57, 95% CI: 1.06-2.35, P=0.03), and individuals without history of hypertension (OR=1.48, 95% CI: 1.08-2.04, P=0.02). Interestingly, there was a significant interaction between age and mtDNA copy number, and between a history of hypertension and mtDNA copy number in elevating ccRCC risk (P for interaction=0.02 and 0.03, respectively). In summary, our data showed that several established risk factors of ccRCC, including advanced age, male sex, smoking, and history of hypertension, negatively impacted mtDNA copy number in PBLs. Lower mtDNA copy number in PBLs was associated with significantly increased risk of ccRCC in younger aged individuals, women, never smokers, and those without a history of hypertension. There was a significant interaction between age and mtDNA, and a history of hypertension and mtDNA in elevating the risk of ccRCC. These findings indicate that the association between mtDNA copy number in PBLs and ccRCC risk may be modified by various host characteristics (age, gender, smoking, and history of hypertension), providing novel insight into the role of mtDNA in modulating RCC tumorigenesis.

Citation Format: Xin Wang, Stephanie Melkonian, Jian Gu, David Chang, Nizar Tannir, Christopher Wood, Xifeng Wu. Mitochondrial DNA copy number in peripheral blood and the risk of clear-cell renal cell carcinoma: Effect of age, gender, smoking, and history of hypertension. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4320. doi:10.1158/1538-7445.AM2014-4320