Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects

Introduction and objective. Chronic obstructive pulmonary disease (COPD) is often accompanied by lung cancer. Among the genes that may play a role in the occurrence of COPD and lung cancer are those encoding the proteolytic enzymes, such as matrix metalloproteinases (MMPs) and their tissue inhibitors. The objective of this study was to find MMPs-associated markers useful in the identification of COPD subjects with increased susceptibility to developing lung cancer. Materials and methods. We compared the frequency of single nucleotide polymorphisms in genes coding for matrix proteinases (MMP1, MMP2, MMP3, MMP9, MMP12) as well as tissue inhibitor of metalloproteinases (TIMP1) in two groups of subjects: COPD patients (54 subjects) and COPD patients diagnosed for lung cancer occurrence (53 subjects). The levels of the respective proteins in blood serum were also analyzed. Results. The frequencies of 2 genotypes, MMP3 rs3025058 and MMP3 rs678815, were significantly different between the studied groups. In both cases, more heterozygotes and less homozygotes (both types) were observed in the COPD group than in the COPD + cancer group. A significantly higher TIMP1 level in blood serum was observed in the COPD + cancer group than in the COPD group. There were no statistically significant differences in MMPs blood levels between the studied groups. In addition, no genotype-associated differences in TIMP1 or MMPs blood levels were observed. Conclusions. Homozygocity for MMP3 rs3025058 and rs678815 polymorphisrns is a potential marker of enhanced susceptibility to lung cancer development among COPD subjects.