Inactivation of p15(INK4b) in chronic arsenic poisoning cases

Arsenic exposure from burning high arsenic-containing coal has been associated with human skin lesion and cancer. However, the mechanisms of arsenic-related carcinogenesis are not fully understood. Inactivation of critical tumor suppression genes by epigenetic regulation or genetic modification might contribute to arsenic-induced carcinogenicity. This study aims to clarify the correlation between arsenic pollution and functional defect of p15(INK4b) gene in arsenic exposure residents from a region of Guizhou Province, China. To this end, 103 arsenic exposure residents and 105 control subjects were recruited in this study. The results showed that the exposure group exhibited higher levels of urinary and hair arsenic compared with the control group (55.28 vs 28.87 μg/L, 5.16 vs 1.36 μg/g). Subjects with higher arsenic concentrations are more likely to have p15(INK4b) methylation and gene deletion (χ(2) = 4.28, P = 0.04 and χ(2) = 4.31, P = 0.04). We also found that the degree of p15(INK4b) hypermethylation and gene deletion occurred at higher incidence in the poisoning cases with skin cancer (3.7% and 14.81% in non-skin cancer group, 41.18% and 47.06 in skin cancer group), and were significantly associated with the stage of skin lesions (χ(2) = 12.82, P < 0.01 and χ(2) = 7.835, P = 0.005). These observations indicate that inactivation of p15(INK4b) through genetic alteration or epigenetic modification is a common event that is associated with arsenic exposure and the development of arsenicosis.