Promoter polymorphisms in matrix metallopeptidase 1 and risk of cutaneous melanoma

Abstract

Matrix metallopeptidase 1 (MMP1) is one of the interstitial collagens in the extracellular matrix metalloproteinase family and involved in tumour behaviours. However, there is no report on the role of genetic variation in MMP1 in risk of cutaneous melanoma (CM). We investigated the association between genotypes and haplotypes of seven reported MMP1 promoter polymorphisms [-1607G ins/del (2G/1G), -839G>A, -755T>G, -519A>G, -422A>T, -340A>G and -320T>C, genotyped by the TaqMan assay] and CM risk in 872 patients and 873 cancer-free controls. These seven polymorphisms were not in linkage disequilibrium among each other (r(2)<0.63). Compared to their common homozygous genotypes, the variant -519GG was associated with significantly decreased CM risk [adjusted odds ratio (OR)=0.71, 95% confidence interval (CI)=0.52-0.99], whereas variants -422TT and -320CC were associated with significantly increased CM risk (OR=1.50, 95% CI=1.11-2.03 and OR=1.72, 95% CI=1.05-2.81, respectively) after adjustment for age, sex, family history and sun-exposure-related risk factors. The number of risk alleles of these three polymorphisms was associated with CM risk in a dose-response manner (P(trend)=0.0002). In the stratification analysis, we found that the associations of these polymorphisms with CM risk were modified by some of the risk factors. Furthermore, the haplotypes Gdel-A-G-A-T-G-T and G-G-G-A-T-A-T were associated with significantly increased CM risk (ORs=1.56 and 2.13, 95% CIs=1.02-2.38 and 1.22-3.70, respectively). These findings suggest that MMP1 promoter polymorphisms may individually or jointly play roles in the development of CM.

Fig. 1

Linkage disequilibrium (LD) for the seven SNPs of MMP1 in r² values.