No association between matrix metalloproteinase (MMP)-1, MMP-3, and MMP-7 SNPs and endometrial cancer risk.

The matrix metalloproteinases (MMP) function as regulators of the dynamic tissue remodeling that occurs in the endometrial lining of the uterus during the normal human menstrual cycle; dysregulation of the MMPs is thought to contribute to the development of both endometriosis and endometrial cancer (1). MMP-1 expression was found to be significantly higher in endometriotic lesions than in surrounding endometrium (2, 3), whereas MMP-3 levels have been reported to be both lower (4) and higher (5) in women with endometriosis compared with women without. MMP-7 expression was found to be significantly higher in endometrial hyperplasia and adenocarcinomas than normal endometrium (6) and, further, was associated with higher grade endometrial tumors (7), and both myometrial (6) and lymph node invasion (8). These three MMP genes are located on the negative strand of chromosome 11, and functional polymorphisms that influence their respective transcription levels have been identified for each (9-12). However, previous studies on MMP SNPs and endometrial cancer are sparse; two studies were found to have evaluated a single MMP-1 single nucleotide polymorphism (SNP) and results were inconsistent. Therefore, this comprehensive study of individual genetic variation across MMP-1, MMP-3, and MMP-7 was undertaken to evaluate associations with endometrial cancer susceptibility.