GSTM1 null polymorphism and susceptibility to endometriosis and ovarian cancer

It is likely that heritable genetic factors contribute to the development o f endometriosis, which is a putative precursor of the endometrioid and clea r cell histological subtypes of ovarian cancer. The phase II glutathione S- transferases (GSTs) are a family of enzymes responsible for metabolism of a broad range of xenobiotics and carcinogens. Allelic variants of GSTs that have impaired detoxification function may increase the rate of genetic dama ge and thereby increase the susceptibility to cancer. The null genetic poly morphism in the gene encoding the GST class mu (GSTM1) enzyme has been repo rted to be significantly elevated in endometriosis patients and may represe nt an endometriosis susceptibility allele. In this study the frequency of t he GSTM1 null genotype was investigated in 84 cases of endometriosis, 293 c ases of ovarian cancer and 219 controls. All cases and controls were derive d from women resident in the south east of England. The frequency of the GS TM1 null allele was not over-represented in the endometriosis patients (47. 6%) compared with the controls (48.9%) (P = 0.898). In the ovarian cancer g roup the GSTM1 null genotype was significantly elevated compared with contr ols (59.0 versus 48.9%, P = 0.025). When stratified according to histologic al subtype a significantly increased GSTM1 null genotype was only observed for the endometrioid (65.4%, P = 0.013) and the combined endometrioid/clear cell ovarian cancers (67.0%, P = 0.004). We conclude that the GSTM1 null a llele is not an endometriosis susceptibility allele, however, it may predis pose endometriotic lesions to malignant transformation to endometrioid and clear cell ovarian cancer.