Bleomycin-induced mutagen sensitivity, passive smoking, and risk of breast cancer in Chinese women: a case–control study

Abstract

It is well recognized that genetic variation as well as environmental factors modulates breast cancer risk. Deficiencies in DNA repair capacity are thought to associate with breast cancer risk. The main aim of this study was to use the mutagen sensitivity assay as an indirect measure of DNA repair capacity to assess breast cancer risk and the relationship between passive smoking and breast cancer risk among women in China. We carried out a case-control study, involving 196 Chinese patients with breast cancer and 211 controls without the disease and with no history of cancer. We investigated the association between mutagen sensitivity and breast cancer risk using bleomycin as the mutagen. Mutagen sensitivity was measured by quantifying the chromatid breaks induced by mutagens in short-term cultures of peripheral blood lymphocytes. Nonparametric tests and the Fisher's exact test were used to determine the statistical significance of the crude case-control comparisons, followed by logistic regression to adjust for important covariates. The mean number of bleomycin-induced breaks per cell was 0.81 for cases compared with 0.73 for the controls (p = 0.016). A greater number of bleomycin-induced chromosomal breaks per cell was associated with an increased risk of breast cancer (adjusted odds ratio of 1.82, p trend <0.01). The association between bleomycin sensitivity and breast cancer risk was greater for women who were exposed to tobacco smoke (passive smokers). The combination of bleomycin sensitivity and exposure to tobacco smoke increased risk further; women passive smokers with high sensitivity to bleomycin had a 2.77-fold increased risk of breast cancer. Our data indicate that increased bleomycin-induced mutagen sensitivity is significantly associated with an increased risk of breast cancer among Chinese women. Exposure to passive smoke is also associated with increased breast cancer risk, and the correlation is even greater for women with both longer passive exposure to tobacco smoke and high sensitivity to bleomycin.