|Title:||Effect of heme oxygenase-1 gene promoter polymorphism on cancer risk by histological subtype: A prospective study in arseniasis-endemic areas in Taiwan||Authors:||Wu, Meei-Maan
|Keywords:||heme oxygenase-1;genetic polymorphism;cancer risk;Bowen's disease;arsenic exposure||Issue Date:||2016||Journal Volume:||138||Journal Issue:||8||Start page/Pages:||1875-1886||Source:||Int. J. Cancer||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 g/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. ;What's new? Heme oxygenase (HO)-1 defends cells against oxidative stress, but its protective effects are modulated by polymorphisms that shorten or lengthen the number of GT dinucleotide repeats in the gene promoter. Here, among cohorts in areas of Taiwan affected by endemic arsenic poisoning, individuals who were homozygous for short (GT)n polymorphisms (S/S, <27 dinucleotide repeats) were found to be at increased risk of skin cancer and lung squamous cell carcinoma. Arsenic exposure further increased skin cancer risk among S/S individuals. All S-allele carriers, however, had a reduced risk of lung adenocarcinoma, a malignancy unrelated to arsenic exposure.
|Appears in Collections:||腫瘤醫學研究所|
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