title: Mitochondrial DNA Content as Risk Factor for Bladder Cancer and Its Association with Mitochondrial DNA Polymorphisms.
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 <0.001). When stratified by host characteristics, advanced age (>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.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Williams
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: David W
authors.initials: DW
authors.lastname: Chang
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xia
authors.initials: X
authors.lastname: Pu
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. xwu@mdanderson.org.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial