Both environmental and endogenous agents have been implicated in the etiology of breast cancer. Case/control studies have suggested that polymorphisms in metabolic enzymes that result in increased activation or decreased detoxification of carcinogens or estrogens may be potential risk factors for breast cancer. However, few attempts have been made to compare the ability of breast tissue to metabolize chemical carcinogens with the types of mutations observed at critical oncogenic loci. In the early phases of this ongoing study, 112 Caucasian breast cancer cases were analyzed for an association between polymorphisms in Phase I and Phase II metabolic enzymes and p53 mutations in tumor tissue. Breast cancer cases exhibited a mutation rate of 16% that may be associated with a younger mean age of onset in the mutation containing population. We have analyzed the GSTM1, GSTT1, and GSTP1I105V, and CYP1B1A119S and L432V genotypes. Although not significant, our results suggest a potential association between the GSTP1I105V polymorphism and p53 mutations (p=0.10). More women with a p53 mutation have at least one CYP1B1119S allele compared to those without a p53 mutation (60% vs. 43%). These associations were not observed with the GSTM1, GSTT1, or CYP1B1L432V genotypes. These results support a previous study suggesting that the GSTP1I105V polymorphism may contribute to p53 mutations. Further analyses with a larger sample size are planned to explore potential interactions between Phase I and Phase II enzymes and mutations in p53. (Supported by NCI grant RO1 81330 and Susan G. Komen Foundation)

[Proc Amer Assoc Cancer Res, Volume 46, 2005]