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Qingyi Wei To test their hypothesis, they evaluated benzo(a)pyrene diol-epoxide (BPDE)-induced mutagen sensitivity and polymorphisms in two different glutathione genes (GSTM1 and GSTT1). BPDE is the primary metabolite of benzo(a)pyrene, a component of cigarette smoke. Glutathione catalyze the detoxification of carcinogen metabolites such as BDPE and reactive oxygen species and therefore, affect the level of in vivo DNA damage. Advance: The investigators established short-term cell culture assays developed from blood samples of 100 breast cancer cases and 105 matched controls which were exposed to a small dose (4 M) of BPDE. The cells were then harvested for cytogenetic analyses. Breast cancer cases had significantly higher chromatid breaks than did controls which translated into a 3-fold higher risk of breast cancer. The risk was higher if the women were under 45 years of age, had ever smoked or were regular alcohol drinkers (4.79, 5.55, and 4.64 respectively). For those women missing the GSTT1 gene, the risk was eight times higher. Implication: These findings suggest that sensitivity to BPDE-induced chromosomal changes may contribute dramatically to the risk of developing breast cancer. This susceptibility may be altered by environmental and genetic factors. Larger studies with more rigorous designs are needed to confirm these findings. Citation: Xiong P, Bondy ML, Li D, Shen H, Wang LE, Singletary SE, Spitz MR, Wei Q. Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case-control study. Cancer Res. 2001 Dec 1;61(23):8465-9. |
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