Melkonian Stephanie C, Wang Xin, Gu Jian, Matin Surena F, Tannir Nizar M, Wood Christopher G, Wu Xifeng
Department of Epidemiology, Department of Urology and Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Urology and.
Carcinogenesis. 2015 Feb;36(2):249-55. doi: 10.1093/carcin/bgu248. Epub 2014 Dec 18.
Variation of mitochondrial DNA copy number (mtDNAcn) in peripheral blood leukocytes has been associated with the risk of various cancers, including renal cell carcinoma (RCC). We assessed the association between mtDNAcn and clear cell RCC (ccRCC) risk in 608 cases and 629 controls frequency-matched on age and gender. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, body mass index, smoking status, history of hypertension, total energy intake and physical activity. Our results suggest an association between low mtDNAcn and ccRCC risk (OR = 1.28, 95% CI: 0.97-1.68, P = 0.09). Lower mtDNAcn was associated with increased ccRCC risk in younger individuals (age <60, OR = 1.68, 95% CI: 1.13-2.49, P = 0.01), women (OR = 1.66, 95% CI: 1.03-2.73, P = 0.04), individuals without history of hypertension (OR = 1.62, 95% CI: 1.09-2.41, P = 0.02) and individuals with low physical activity levels (OR = 1.55, 95% CI: 1.02-2.37, P = 0.05). We observed significant and marginally significant interactions between both age and history of hypertension and mtDNAcn in elevating ccRCC risk (P for interaction = 0.04 and 0.07, respectively). Additionally, low mtDNAcn was associated with ccRCC risk in younger individuals with low levels of physical activity [ORs and 95% CI for medium and low physical activity levels, respectively, 2.31 (1.18-4.52) and 2.09 (1.17-3.75), P interaction = 0.04]. To our knowledge, this is the first report to investigate the role of mtDNAcn in the ccRCC subtype and the first to suggest that this association may be modified by risk factors including age, gender, history of hypertension and physical activity.
外周血白细胞中线粒体DNA拷贝数（mtDNAcn）的变化与包括肾细胞癌（RCC）在内的多种癌症风险相关。我们评估了608例病例和629例年龄和性别频率匹配的对照中mtDNAcn与透明细胞肾细胞癌（ccRCC）风险之间的关联。使用无条件逻辑回归来估计比值比（OR）和95%置信区间（CI），并对年龄、性别、体重指数、吸烟状况、高血压病史、总能量摄入和身体活动进行了调整。我们的结果表明低mtDNAcn与ccRCC风险之间存在关联（OR = 1.28，95% CI：0.97 - 1.68，P = 0.09）。较低的mtDNAcn与较年轻个体（年龄<60岁，OR = 1.68，95% CI：1.13 - 2.49，P = 0.01）、女性（OR = 1.66，95% CI：1.03 - 2.73，P = 0.04）、无高血压病史的个体（OR = 1.62，95% CI：1.09 - 2.41，P = 0.02）以及身体活动水平低的个体（OR = 1.55，95% CI：1.02 - 2.37，P = 0.05）的ccRCC风险增加相关。我们观察到年龄和高血压病史与mtDNAcn在增加ccRCC风险方面存在显著和边缘显著的相互作用（交互作用P值分别为0.04和0.07）。此外，低mtDNAcn与身体活动水平低且年龄较轻的个体的ccRCC风险相关[中等和低身体活动水平的OR和95% CI分别为2.31（1.18 - 4.52）和2.09（1.17 - 3.75），P交互作用 = 0.04]。据我们所知，这是第一份研究mtDNAcn在ccRCC亚型中的作用的报告，也是第一份表明这种关联可能会受到年龄、性别、高血压病史和身体活动等风险因素影响的报告。
