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Open Access Research article

Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma

Astrid Lièvre1, Jacqueline Milet23, Jérôme Carayol2, Delphine Le Corre1, Chantal Milan4, Alexandre Pariente5, Bernard Nalet6, Jacques Lafon7, Jean Faivre4, Claire Bonithon-Kopp4, Sylviane Olschwang8, Catherine Bonaiti-Pellié23, Pierre Laurent-Puig1* and members of the ANGH group

Author Affiliations

1 INSERM U775 et Université René Descartes, Paris, France

2 INSERM, U535, Villejuif, France

3 Université Paris-Sud, IFR69, Villejuif, France

4 INSERM E106, Faculté de Médecine, Dijon, France

5 Centre Hospitalier, Pau, France

6 Centre Hospitalier, Montélimar, France

7 Centre Hospitalier, Aix-en-Provence, France

8 INSERM U599, Institut Paoli Calmettes, Marseille, France

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BMC Cancer 2006, 6:270  doi:10.1186/1471-2407-6-270

Published: 24 November 2006

Abstract

Background

Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls.

Methods

Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression.

Results

No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95%CI: 1.20–2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95%CI: 1.08–3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression.

Conclusion

These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis.