Cell-type-dependent associations of heme oxygenase-1 GT-repeat polymorphisms with the cancer risk in arsenic-exposed individuals: A preliminary report

Heme oxygenase (HO)-1 is highly up-regulated by many stressful stimuli, including arsenic. A GT-repeat polymorphism in the HO-1 gene promoter can inversely modulate the levels of HO-1 induction. Long-term digestion of arsenic-contaminated drinking water may cause cancers of anatomic variety. We carried out this study to examine the correlation of HO-1 GT-repeat polymorphism with cancer risk in arsenic-exposed individuals during a 10-year follow-up. A total of 1,004 participants who had HO-1 genotyping available from two arsenicosis-endemic areas in Taiwan were included. Baseline characteristics derived from questionnaire interview were collected in 1988-1990 for the subjects of the BFD-endemic area and in 1996-1998 the subjects of the Lanyang Basin area. Allelic GT-repeats were categorized into short (S, 150 μg/L-year. Carriers of S/S genotype had a significantly increased risk of non-melanoma skin cancer [HR 3.05 (95% CI, 1.24-7.48), P = 0.015] as compared to those who carried L/L genotype for the entire subjects. Regarding liver and intrahepatic bile ducts cancer, carriers of S/S genotype also had a significantly increased risk [HR 4.14 (95% CI, 1.30-13.21), P = 0.016] when compared to those carried L/S genotype. We provided evidence that HO-1 gene variants may modify the carcinogenic effect of arsenic in a cell-type-dependent pattern.