Influence of single nucleotide polymorphisms in the MMP1 promoter region on cutaneous melanoma progression

摘要

Recently, we reported on the associations of seven single nucleotide polymorphisms (SNPs) in the promoter region of MMP1 gene with susceptibility to cutaneous melanoma (CM). Considering the reported correlation between MMP1 expression and melanoma progression, we hypothesized that these promoter SNPs might affect CM progression and prognosis. In this study, we examined the associations of seven SNPs with overall survival, as well as six clinicopathological factors in 754 patients with CM. After adjustment for 11 covariates, we observed significant associations of the SNP - 422A >T (rs475007) with ulceration status (P = 0.012), primary tumor thickness (P = 0.040), and anatomic site (P= 0.030). We also observed significant associations of the SNP - 755T >G (rs498186) with ulceration status (P =0.038) and anatomic site (P = 0.003). Two SNPs, - 839G> A and - 519A >G, were marginally associated with primary tumor thickness, ulceration status, and anatomic site. Furthermore, the frequency of haplotype 2G-G-G-A-A-G-T was higher in patients with ulceration (odds ratio = 2.18, 95% confidence interval: 1.08-4.40, P = 0.030) compared with those without ulceration. However, we did not find significant associations of these SNPs with overall survival and other clinical factors. As primary tumor thickness and ulceration status are two important indicators of tumor progression and have significant associations with melanoma prognosis, our results suggested that these promoter SNPs in MMP1 might have potential effects on melanoma progression and prognosis by influencing related clinical factors. Melanoma Res 22:169-175