Wang Y.-H.Yeh S.-D.Wu M.-M.Liu C.-T.Shen C.-H.Shen K.-H.YEONG-SHIAU PUHsu L.-I.Chiou H.-Y.Chen C.-J.2021-02-022021-02-0220130304-3894https://www.scopus.com/inward/record.uri?eid=2-s2.0-84887617414&doi=10.1016%2fj.jhazmat.2012.08.056&partnerID=40&md5=06bd321af09bde37d0eaed65338f05bbhttps://scholars.lib.ntu.edu.tw/handle/123456789/544386Arsenic 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. ? 2012 Elsevier B.V.Arsenic; Bladder cancer; Cigarette smoking; Upper urinary tract; Urothelial carcinoma; Vascular endothelial growth factor[SDGs]SDG3Arsenic; Diseases; Endothelial cells; Genes; Bladder cancers; Cigarette smoking; Urinary tract; Urothelial carcinoma; Vascular endothelial growth factor; Risk perception; arsenic; vasculotropin; arsenic; cancer; comparative study; genotype-environment interaction; health risk; histopathology; pollution effect; pollution exposure; smoking; temporal period; vascular plant; adult; aged; alcohol consumption; article; bladder cancer; cancer grading; cancer risk; cancer staging; controlled study; distant metastasis; environmental exposure; female; genotype; hospital based case control study; human; lymph node; major clinical study; male; single nucleotide polymorphism; smoking; transitional cell carcinoma; upper urinary tract urothelial carcinoma; 95% CI; 95% confidence interval; Arsenic; Bladder cancer; Cigarette smoking; Hardy-Weinberg equilibrium; HWE; LD; linkage disequilibrium; odds ratio; OR; PAHs; PCR-RFLP; polycyclic aromatic hydrocarbons; polymerase chain reaction-restriction fragment length polymorphism; reactive oxygen species; ROS; single nucleotide polymorphism; SNP; UC; Upper urinary tract; Urothelial carcinoma; urothelial carcinoma; Vascular endothelial growth factor; vascular endothelial growth factor; VEGF; Aged; Arsenic; Carcinoma; Case-Control Studies; Environmental Exposure; Female; Genotype; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Residence Characteristics; Risk; Risk Factors; Smoking; Urinary Bladder Neoplasms; Urothelium; Vascular Endothelial Growth Factor Ajournal article10.1016/j.jhazmat.2012.08.056230097952-s2.0-84887617414