Background: We recently reported that the main reason for the documented higher prevalence of arsenic-related skin lesions among men than among women is the result of less efficient arsenic metabolism.

Objective: Because smoking has been associated with less efficient arsenic methylation, we aimed to elucidate interactions between tobacco use and arsenic metabolism for the risk of developing skin lesions.

Methods: We used a population-based case-referent study that showed increased risk for skin lesions in relation to chronic arsenic exposure via drinking water in Bangladesh and randomly selected 526 of the referents (random sample of inhabitants > 4 years old; 47% male) and all 504 cases (54% male) with arsenic-related skin lesions to measure arsenic metabolites [methylarsonic acid (MA) and dimethylarsinic acid (DMA)] in urine using high-performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICPMS).

Results: The odds ratio for skin lesions was almost three times higher in the highest tertile of urinary %MA than in the lowest tertile. Men who smoked cigarettes and bidis (locally produced cigarettes; 33% of referents, 58% of cases) had a significantly higher risk for skin lesions than did nonsmoking men; this association decreased slightly after accounting for arsenic metabolism. Only two women smoked, but women who chewed tobacco (21% of referents, 43% of cases) had a considerably higher risk of skin lesions than did women who did not use tobacco. The odds ratio (OR) for women who chewed tobacco and who had < or = 7.9%MA was 3.8 [95% confidence interval (CI), 1.4-10] compared with women in the same MA tertile who did not use tobacco. In the highest tertile of %MA or %inorganic arsenic (iAs), women who chewed tobacco had ORs of 7.3 and 7.5, respectively, compared with women in the lowest tertiles who did not use tobacco.

Conclusion: The increased risk of arsenic-related skin lesions in male smokers compared with nonsmokers appears to be partly explained by impaired arsenic methylation, while there seemed to be an excess risk due to interaction between chewing tobacco and arsenic metabolism in women.