Polymorphisms at the glutathione S-transferase GSTM1, GSTT1 and GSTP1 loci: risk of ovarian cancer by histological subtype

The phase II glutathione S-transferases (GSTs) GSTT1, GSTM1 and GSTP1 catal yse glutathione-mediated reduction of exogenous and endogenous electrophile s. These GSTs have broad and overlapping substrate specificities and it has been hypothesized that allelic variants associated with less effective det oxification of potential carcinogens may confer an increased susceptibility to cancer. To assess the role of GST gene variants in ovarian cancer devel opment, we screened 285 epithelial ovarian cancer cases and 299 unaffected controls for the GSTT1 deletion (null) variant, the GSTM1 deletion (null) v ariant and the GSTP1 codon 104 A-->G Ile-->Val amino acid substitution vari ant, The frequencies of the GSTT1, GSTM1 and GSTP1 polymorphic variants did not vary with tumour behaviour (low malignant potential or invasive) or p5 3 immunohistochemical status. There was a suggestion that ovarian cancers o f the endometrioid or clear cell histological subtype had a higher frequenc y of the GSTT1 and GSTM1 deletion genotype than other histological subgroup s. The GSTT1, GSTM1 and GSTP1 genotype distributions did not differ signifi cantly between unaffected controls and ovarian cancer cases (overall or inv asive cancers only). However, the GSTM1 null genotype was associated with i ncreased risk of endometrioid/clear cell invasive cancer [age-adjusted OR ( 95% CI) = 2.04 (1.01-4.09), P = 0.05], suggesting that deletion of GSTM1 ma y increase the risk of ovarian cancer of these histological subtypes specif ically. This marginally significant finding will require verification by in dependent studies.