Background & objective: Matrix metalloproteinases (MMPs) might be involved in invasion and metastasis of tumors by degrading extracellular matrix (ECM) and basement membrane (BM). The 5A or 6A single nucleotide polymorphism (SNP) at the -1 171 bp site of promoter region of MMP-3 may modify the transcription and local expression of MMP-3. This study was to investigate correlation of the MMP-3 SNP with genetic susceptibility and lymph node metastasis of non-small cell lung cancer (NSCLC).
Methods: Genotypes of the MMP-3 SNP of 173 NSCLC patients and 350 healthy controls were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results: Distributions of the MMP-3 genotypes in both NSCLC patients and healthy controls were accorded with Hardy-Weinberg equilibrium (P>0.05). Frequencies of the 6A/6A, 5A/6A, and 5A/5A genotypes were 65.3%, 30.6%, and 4.1% in NSCLC patients, and 67.7%, 30.0%, and 2.3% in healthy controls, whereas frequencies of the 6A and 5A alleles were 79.3% and 20.7% in NSCLC patients, and 82.7% and 17.3% in healthy controls. The overall genotype and allelotype distributions among NSCLC patients and healthy controls were similar (P>0.05). However, stratified analysis found that frequency of the 5A allele was significantly higher in smoking patients than in healthy smokers (21.0% vs. 12.9%, P=0.03). Therefore, smokers with the 5A/6A or 5A/5A genotype have higher risk of developing NSCLC [age and sex adjusted odds ratio (OR) =2.07, 95% confidence interval (CI) =1.13-3.78]. When stratified by pathologic types, no significant difference in MMP-3 genotype or allelotype distribution between adenocarcinoma patients, squamous carcinoma patients and healthy controls was shown. When further stratified by lymphatic metastasis status, frequencies of the 5A allele and the 5A/5A genotype were significantly higher in NSCLC patients with lymphatic metastasis than in NSCLC patients without lymphatic metastasis (22.8% vs. 11.8%, P=0.02u 8.6% vs. 0%, P=0.02). Thus, NSCLC patients with the 5A/5A genotype have higher risk of lymphatic metastasis than NSCLC patients with the 6A/6A genotype (OR=12.38, 95% CI=0.76-202.13).
Conclusions: The 5A allele of MMP-3 might be associated with the increased susceptibility to NSCLC among smokers. The 5A homozygote might increase the risk of lymphatic metastasis in NSCLC patients.