Progression of human breast cancers to the metastatic state is linked to genotypes of catechol-O-methyltransferase

There is increasing evidence that catecholestrogens may contribute to the d evelopment of breast cancer. Specifically, inactivation of catecholestrogen s may prevent the genesis and arrest the progression of the disease. Catech ol-O-methyltransferase (COMT), Glutathione S-transferase (GST) M1 and GSTP1 . are responsible for the detoxification of catecholestrogens, and are poly morphic in the human population. In this study, a PCR-based restriction fra gment length polymorphism analysis was performed to determine genotypes of the COMT, GSTM1 anti GSTP1 genes. We investigated the relationship between the germline polymorphism of these genes and clinico-pathological character istics in 140 patients with breast cancer. Among 73 patients with the low a ctivity COMT allele, 49 (67%) had regional lymph node metastasis. On the ot her hand, only 27 (40%) of 67 patients without the low activity allele had lymph node metastasis. The COMT genotype was significantly associated with clinical stage and the extent of regional lymph node metastasis of breast c ancer (P < 0.05). However, polymorphisms of the GSTM1 and GSTP1 gene were n ot associated with clinico-pathological factors. Our findings suggest that the allele encoding for low activity COMT may contribute to the progression of breast cancer. (C) 2000 Elsevier Science Ireland Ltd. All rights reserv ed.