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The glutathione S-transferases (GSTs), including the GSTM1, GSTP1, and GSTT1 isoenzymes, are a phase II metabolizing enzyme family involved in the detoxification of a wide range of xenobiotics and carcinogens. Common deletion of the GSTM1 and GSTT1 genes, as well as the GSTP1 313A>G (Ile105Val) polymorphism may alter enzyme activity and possibly modify cancer risk. Polymorphisms in these genes have been associated with susceptibility to various cancers, including ovarian tumors. However, the results have been inconclusive and the underlying mechanisms remain unclear. We used data from a multiethnic case-control study conducted in Hawaii between 1994 and 2004 to examine the association of the GST- M1, P1, and T1 polymorphisms with ovarian cancer risk. Among 263 cases and 457 controls, carriers of the GSTP1 313G variant had a significantly reduced risk for ovarian cancer (OR=0.65, 95%CI: 0.49-0.98) (p for gene-dosage effect: 0.05), compared to women without the variant allele. No overall association was seen among women with the homozygous deletion of GSTM1 (null) (OR=1.11, 95% CI: 0.79-1.55) or GSTT1 (OR=1.13, 95% CI: 0.78-1.53) genotypes. No significant interactions existed between ethnicity and GST polymorphisms. GSTM1 null was significantly associated with an incresaed risk of low malignant potential tumors (OR=2.54, 95% CI: 1.18-5.51) but not invasive tumors (p for the difference =0.013). We also observed a marginal differential association between GSTM1 null genotype and ovarian subtypes (p=0.05), with a positive effect on non-endometeriod/clear cell types (OR=1.24), while with a negative effect on endometeriod/clear cell types (OR=0.68). Neither family history of breast and/or ovarian cancer, nor smoking or alcohol drinking history, modified the associations for GST polymorphisms. Our data suggest a possible inverse association of GSTP1 313G allele with ovarian cancer risk.

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