Passive smoking, NAT2 polymorphism, and breast cancer risk in Israeli Arab women: a case–control study

Background: The effect of passive smoking (PS) on breast cancer (BC) is controversial, and may be modified by polymorphism of the N-Acetyl-transferase (NAT) 2 enzyme which is involved in tobacco carcinogen metabolism. We aimed to evaluate the relationship between PS and BC by NAT2 variants in Arab–Israeli women, a unique population with low active smoking rates, and high exposure to PS. Methods: A population-based case-control study was carried out on non-smoking 137 prevalent breast cancer patients and 274 population-based controls, aged 30–70 years. Data on past and current PS, sociodemographic, and other characteristics were retrieved through interviews, and buccal smears were provided for NAT2 analyses. Logistic regression models adjusting for potential confounders assessed the odds ratios (ORs) and 95% confidence intervals (95% CI) of the association between PS and BC. Results: Ever PS was associated with increased BC risk: OR = 2.22, 95% CI 1.28–3.87. Higher lifetime PS exposure was associated with higher BC risk: Compared to never exposed women, women exposed to PS most of their lives had a threefold higher BC risk (OR = 3.16, 95% CI 1.70–5.87, P_trend < 0.001). NAT2 polymorphism did not modify these associations. Conclusions: PS exposure in non-smoking Israeli Arab women is significantly associated with increased risk for BC, potentially allowing for specific intervention; NAT2 polymorphism does not modify this association.