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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 severalMMPpromoters 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 theMMP1promoter and the adenosine insertion polymorphism in theMMP3promoter, on risk of the development and lymphatic metastasis of non-small cell lung carcinoma (NSCLC). TheMMP1andMMP3SNPs 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 (allPvalues are above 0.05). However, stratification analysis showed that smoking individuals with theMMP3 5Aallele had a &gt;1.5-fold increased risk to develop NSCLC, compared with those harboring the6Ahomozygous [the age and gender adjusted odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.04–2.70]. In addition, the frequency of theMMP3 5Ahomozygote in NSCLC patients with lymphatic metastasis was significantly higher than that in lymph node negative ones (5.7 versus 0%,P= 0.04). Moreover, theMMP 1G/5Ahaplotype significantly increased the risk of lymphatic metastasis (OR = 3.36, 95% CI = 1.42–7.94), compared with the2G/6Ahaplotype. The present result suggested that theMMP3promoter polymorphism may modify susceptibility to NSCLC, and theMMP 1G/5Ahaplotype may predicate the risk of lymphatic metastasis of this tumor.

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