title: Effect of heme oxygenase-1 gene promoter polymorphism on cancer risk by histological subtype: A prospective study in arseniasis-endemic areas in Taiwan.
abstract: Heme oxygenase (HO)-1 is upregulated by many stressful stimuli, including arsenic. A GT-repeat ((GT)n) polymorphism in the HO-1 gene promoter inversely modulates the levels of HO-1 induction. Previous HO-1 (GT)n polymorphism studies in relation to cancer risk have shown disparate results. We prospectively investigated the associations between HO-1 (GT)n polymorphism and cancer risk related to arsenic from drinking water. Totally, 1,013 participants from community-based cohorts of arseniasis-endemic areas in Taiwan were followed for 13 years. Allelic polymorphisms were classified into long (L, ≥ 27 (GT)n) and short (S, <27 (GT)n). Newly developed cases were identified through linkage with National Cancer Registry of Taiwan. Multivariate Cox proportional hazard methods were used to evaluate effects of the HO-1 polymorphism alone or combined with arsenic exposure. Results showed that participants with the S/S genotype had an increased risk of Bowen's disease (HR = 10.49; 95% CI: 2.77-39.7), invasive skin cancer (HR = 2.99; 95% CI: 1.13-7.87), and lung squamous cell carcinoma (HR = 3.39; 95% CI: 1.15-9.95) versus those with L/S or L/L genotype. The S/S genotype combined with high arsenic exposure (>300 μg/L) had a greater risk of skin cancer compared to the genotype alone. Consistent with previous findings, participants with the S-allele had a reduced risk of lung adenocarcinoma (HR = 0.21; 95% CI: 0.03-0.68) versus those with L/L genotype. There were no significant differences in risk of urothelial carcinoma among the three genotypes. Associations of HO-1 (GT)n polymorphism with cancer risk differs by histological subtype and the polymorphism should be considered a modifier in the risk assessment of arsenic exposure.
authors.affiliation: School of Public Health, Taipei Medical University, Taipei, Taiwan.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Meei-Maan
authors.initials: MM
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung and Chang Gung University College of Medicine, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Ling-I
authors.initials: LI
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors.forename: Yuang-Hung
authors.initials: YH
authors.lastname: Wang
authors.affiliation: School of Public Health, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D020261:Arsenic Poisoning / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D060766:Drinking Water / Q000009:adverse effects; D019353:Endemic Diseases; D005260:Female; D005455:Fluorescent Antibody Technique; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D016016:Proportional Hazards Models; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013624:Taiwan / Q000453:epidemiology
chemical_list: D060766:Drinking Water; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Bowen's disease; arsenic exposure; cancer risk; genetic polymorphism; heme oxygenase-1