Functional polymorphisms in the promoter regions of MMP2 and MMP3 are not associated with melanoma progression

Javier Cotignola¹ , Pampa Roy¹ , Ami Patel² , Nicole Ishill¹ , Shivang Shah¹ , Alan Houghton² , Daniel Coit³ , Allan Halpern² , Klaus Busam⁴ , Marianne Berwick⁵ and Irene Orlow¹

¹Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

²Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

³Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

⁴Pathology Department, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

⁵Division of Epidemiology, University of New Mexico, Albuquerque, NM, USA

author email corresponding author email

Journal of Negative Results in BioMedicine 2007, 6:9doi:10.1186/1477-5751-6-9


Published:	24 October 2007

Abstract

Background

The matrix metalloproteinases (MMPs) are enzymes that cleave various components of the extracellular matrix (ECM) and basement membranes. MMPs are expressed in melanocytes and their overexpression has been linked to tumor development, progression and metastasis. At the genetic level, the following functional promoter polymorphisms are known to modify the gene transcription: -1306 C/T and -735 C/T in the MMP2 gene, and -1171 5A/6A in the MMP3 gene. Functional polymorphisms in MMP genes' promoter regions may modulate the risk for melanoma progression.

Methods

We evaluated MMP2 and MMP3 germline polymorphisms in a group of 1002 melanoma patients using PCR-based methods, including fragment size analysis and melting temperature profiles. Two-sided Chi-Square, Cochran-Armitage tests for trend, Fisher's exact tests, and Kendall's Tau tests were performed to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known melanoma confounders such as age, sex, phenotypic index, moles, freckles, and race. Survival estimates were computed using the Kaplan-Meier method and differences in survival were assessed using the log rank test.

Results

All genotypes were in Hardy-Weinberg equilibrium. After adjustment for age, sex and phenotypic characteristics of melanoma risk, no significant associations were identified with the clinical, pathological, and epidemiological variables studied. The melting profile for MMP2 -735 C/T identified a new change in one sample. A new PCR-amplification followed by direct sequencing confirmed a heterozygote G to A substitution at position -729.

Conclusion

This study does not provide strong evidence for further investigation into the role of the MMP2 and MMP3 variants in melanoma progression.