Mitochondrial DNA content as risk factor for bladder cancer and its association with mitochondrial DNA polymorphisms

Stephen Williams, Yuanqing Ye, Maosheng Huang, David W. Chang, Ashish M. Kamat, Xia Pu, Colin P. Dinney, Xifeng Wu

Research output: Contribution to journalArticle

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Abstract

Mitochondrial DNA (mtDNA) content has been shown to be associated with cancer susceptibility. We identified 926 bladder cancer patients and compared these with 926 healthy controls frequency matched on age, gender, and ethnicity. Patients diagnosed with bladder cancer had significantly decreased mtDNA content when compared with control subjects (median, 0.98 vs. 1.04, P <0.001). Low mtDNA content (i.e., 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% confidence interval (CI), 1.13-1.66; 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 (Ptrend 65 years), male sex and positive smoking history were 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 (Pinteraction = 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 biologic underpinnings of bladder carcinogenesis.

Original languageEnglish (US)
Pages (from-to)607-613
Number of pages7
JournalCancer Prevention Research
Volume8
Issue number7
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

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Mitochondrial DNA
Urinary Bladder Neoplasms
Odds Ratio
Confidence Intervals
Carcinogenesis
Urinary Bladder
Smoking
History
Alleles

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mitochondrial DNA content as risk factor for bladder cancer and its association with mitochondrial DNA polymorphisms. / Williams, Stephen; Ye, Yuanqing; Huang, Maosheng; Chang, David W.; Kamat, Ashish M.; Pu, Xia; Dinney, Colin P.; Wu, Xifeng.

In: Cancer Prevention Research, Vol. 8, No. 7, 01.07.2015, p. 607-613.

Research output: Contribution to journalArticle

Williams, Stephen ; Ye, Yuanqing ; Huang, Maosheng ; Chang, David W. ; Kamat, Ashish M. ; Pu, Xia ; Dinney, Colin P. ; Wu, Xifeng. / Mitochondrial DNA content as risk factor for bladder cancer and its association with mitochondrial DNA polymorphisms. In: Cancer Prevention Research. 2015 ; Vol. 8, No. 7. pp. 607-613.
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abstract = "Mitochondrial DNA (mtDNA) content has been shown to be associated with cancer susceptibility. We identified 926 bladder cancer patients and compared these with 926 healthy controls frequency matched on age, gender, and ethnicity. Patients diagnosed with bladder cancer had significantly decreased mtDNA content when compared with control subjects (median, 0.98 vs. 1.04, P <0.001). Low mtDNA content (i.e., 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{\%} confidence interval (CI), 1.13-1.66; 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 (Ptrend 65 years), male sex and positive smoking history were 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 (Pinteraction = 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 biologic underpinnings of bladder carcinogenesis.",
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