Mitochondrial DNA Content as Risk Factor for Bladder Cancer and Its Association with Mitochondrial DNA Polymorphisms.
Mitochondrial DNA Content as Risk Factor for Bladder Cancer and Its Association with Mitochondrial DNA Polymorphisms.
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DOI：
10.1158/1940-6207.capr-14-0414
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Williams SB;Ye Y;Huang M;Chang DW;Kamat AM;Pu X;Dinney CP;Wu X
Mitochondrial DNA (mtDNA) content has been shown to be associated with cancer susceptibility. We identified 926 bladder cancer patients and compared these to 926 healthy-controls frequency matched on age, gender, and ethnicity. Patients diagnosed with bladder cancer had significantly decreased mtDNA content when compared to control subjects (median: 0.98 vs. 1.04, p<0.001). Low mtDNA content (ie, less than the median in control subjects) was associated with a statistically significant increased risk of bladder cancer, when compared with high mtDNA content (Odds Ratio (OR) = 1.37, 95% CI = 1.13 to 1.66, p<0.001). In a trend analysis, a statistically significant dose–response relationship was detected between lower mtDNA content and increasing risk of bladder cancer (P for trend <0.001). When stratified by host characteristics, advanced age (>65 years), male/female sex and positive smoking history were all significantly associated with low mtDNA content and increased risk of bladder cancer. We identified two unique mtDNA polymorphisms significantly associated with risk of bladder cancer: mitot10464c (OR=1.39 95%CI: 1.00–1.93, p=0.048) and mitoa4918g (OR=1.40, 95% CI: 1.00–1.95, p=0.049). Analysis of the joint effect of low mtDNA content and unfavorable mtDNA polymorphisms revealed a 2.5 fold increased risk of bladder cancer (OR=2.50, 95% CI: 1.60–3.94, p<0.001). Significant interaction was observed between mitoa4918g and mtDNA content (p for interaction = 0.028). Low mtDNA content was associated with increased risk of bladder cancer and we identified new susceptibility mtDNA alleles associated with increased risk that require further investigation into the biological underpinnings of bladder carcinogenesis.
