Matrix metalloproteinase 1 gene polymorphism as a prognostic predictor of invasive cervical cancer

Objectives. Whereas human papillomavirus (HPV) infection is the major determinant of cervical carcinogenesis, host genetic factors may confer individual susceptibility and prognosis. Matrix metalloproteinase 1 (MMP-1) is an important modulator of carcinogenesis. A guanine insertion (2G) polymorphism at nucleotide -1607 of the MMP-1 gene promoter creates an Ets-1-binding site, which increases transcription activity. The present study investigates the association between MMP-1 polymorphism and cervical neoplasia, and their prognostic significance. Methods. In this study, the MMP-1 polymorphism was assessed in 135 high-grade squamous intraepithelial lesions (HSILs) and 197 invasive squamous cell carcinomas (SCCs), and in age-matched controls, by capillary electrophoresis. The association of clinicopathological factors and HPV status with MMP-1 genotypes was tested. Result. Frequencies of the 2G allele in HSIL and SCC were 64% and 65%, respectively, which did not differ significantly from control values (66% and 64%, respectively). The 2G allele was associated with advanced stages of disease (P = 0.03), whereas the G allele was more common in patients with regional lymph node metastases (P = 0.02). The survival time in patients with the heterozygous genotype G/2G (median, 55.3 months) was significantly longer than those with either the G/G (50.3 months) or 2G/2G genotype (43.9 months) (P = 0.02). No significant correlation between HPV status and MMP-1 genotype was identified. Conclusions. The genetic polymorphisms of MMP-1 are not associated with the risk of HSIL and SCC, but with the invasiveness and prognosis of SCC. The heterozygous genotype of MMP-1 can be used as a prognostic marker in patients with invasive cervical cancer. (C) 2004 Elsevier Inc. All rights reserved.