Polymorphisms in the MMP1 and MMP3 promoter and non-small cell lung carcinoma in North China

Abstract

Matrix metalloproteinases (MMPs) are proteolytic enzymes that regulate various cell behaviors in cancer biology, via their basic function of degradation of proteins. Genetic variations in several MMP promoters may influence transcription and expression of MMPs. The aim of this study is to assess the effects of the two single nucleotide polymorphisms (SNPs), the guanine insertion polymorphism in the MMP1 promoter and the adenosine insertion polymorphism in the MMP3 promoter, on risk of the development and lymphatic metastasis of non-small cell lung carcinoma (NSCLC). The MMP1 and MMP3 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 243 NSCLC patients and 350 control subjects in North China. The overall genotype and allelotype distribution of both the variants in cancer patients and controls was not significantly different (all P values are above 0.05). However, stratification analysis showed that smoking individuals with the MMP3 5A allele had a >1.5-fold increased risk to develop NSCLC, compared with those harboring the 6A homozygous [the age and gender adjusted odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.04-2.70]. In addition, the frequency of the MMP3 5A homozygote in NSCLC patients with lymphatic metastasis was significantly higher than that in lymph node negative ones (5.7 versus 0%, P = 0.04). Moreover, the MMP 1G/5A haplotype significantly increased the risk of lymphatic metastasis (OR = 3.36, 95% CI = 1.42-7.94), compared with the 2G/6A haplotype. The present result suggested that the MMP3 promoter polymorphism may modify susceptibility to NSCLC, and the MMP 1G/5A haplotype may predicate the risk of lymphatic metastasis of this tumor. © Oxford University Press 2005; all rights reserved.