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

摘要

Heme oxygenase (HO)-l 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, <27 GT-repeats) and long (L, >27 GT-repeats). Analysis results showed that there were no significant differences in the risk of urinary tract cancer among the three genotype groups after accounting for age, gender, average arsenic exposure, smoking status, and alcohol intake. However, for cancer of trachea bronchus and lung, carriers of L/S genotype versus L/L group had significantly reduced risk [HR 0.34 (95% CI, 0.13-0.95), P = 0.039] while restricting subgroup of study subjects to arsenic levels >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.