title: Comparing the joint effect of arsenic exposure, cigarette smoking and risk genotypes of vascular endothelial growth factor on upper urinary tract urothelial carcinoma and bladder cancer.
abstract: Arsenic exposure and cigarette smoking are environmental risk factors for urothelial carcinoma (UC). Vascular endothelial growth factor (VEGF) is the key regulator of angiogenesis in various malignancies. This study investigates the joint effect of arsenic exposure, cigarette smoking, and VEGF polymorphisms on UC risk. This was a hospital-based case-control study consisting of 730 histopathologically confirmed UC cases, including 470 bladder cancers, 260 upper urinary tract UCs (UUTUCs), and 850 age-matched controls, recruited from September 1998 to December 2009. UC risk was estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. Ever smokers with high arsenic exposure had significantly increased risks of 5.7 and 6.4 for bladder cancer and UUTUC, respectively. Moreover, ever smokers with high arsenic exposure carrying 1 or 2 risk genotypes of the VEGF gene had a significantly increased risk of 6.6 for bladder cancer and a strikingly higher risk of 9.9 for UUTUC. Additionally, UUTUC cases with high arsenic exposure carrying 1 or 2 risk genotypes of the VEGF gene had a non-significant increased risk of advanced tumor stage. Our findings suggest that arsenic exposure, cigarette smoking, and risk genotypes of VEGF contribute to a higher risk of UUTUC than of bladder cancer.
authors.affiliation: School of Public Health, Taipei Medical University, Taipei, Taiwan; Division of Urology, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Hung
authors.initials: YH
authors.lastname: Wang
authors.forename: Shauh-Der
authors.initials: SD
authors.lastname: Yeh
authors.forename: Meei-Maan
authors.initials: MM
authors.lastname: Wu
authors.forename: Chi-Tung
authors.initials: CT
authors.lastname: Liu
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Shen
authors.forename: Kun-Hung
authors.initials: KH
authors.lastname: Shen
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
authors.forename: Ling-I
authors.initials: LI
authors.lastname: Hsu
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000368:Aged; D001151:Arsenic / Q000737:chemistry / Q000633:toxicity*; D002277:Carcinoma / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D006760:Hospitalization; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012111:Residence Characteristics; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000235:genetics; D019459:Urothelium / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D001151:Arsenic