Journal Article

Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cancer

Li Su, Wei Zhou, Kofi Asomaning, Xihong Lin, John C. Wain, Thomas J. Lynch, Geoffrey Liu and David C. Christiani

in Carcinogenesis

Volume 27, issue 5, pages 1024-1029
Published in print May 2006 | ISSN: 0143-3334
Published online November 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi283
Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cancer

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The MMPs (matrix metalloproteinases) are a family of secreted zinc metalloproteases that degrade the collagens of the extracellular matrix important in tissue remodeling and repair during development and inflammation. We investigated the associations between polymorphisms of MMP-1 (-1607 1G/2G, rs1799750), MMP-3 (-1171 5A/6A, rs3025058), and MMP-12 (-82AG, rs2276109, and 1082A/G, rs652438) and the risk of lung cancer in 2014 Caucasian lung cancer patients and 1323 healthy controls. The results were analyzed using logistic regression models, adjusting for covariates. The four polymorphisms were in Hardy-Weinberg disequilibrium. Except for the 1G-1082A, the other linkage disequilibrium tests between the four MMP polymorphisms were statistically significant (P < 0.001). There was no overall association between individual MMP polymorphism and the risk of lung cancer. The MMP polymorphisms jointly were associated with a non-statistically significant higher risk of lung cancer, with the adjusted odds ratio (AOR) of subjects with 5+ variant alleles versus zero variant allele of 1.31 [95% confidence interval (CI), 0.92–1.88]. Stronger associations were observed in never-smokers and males, with the corresponding AORs of 2.44 (95%CI, 1.10–5.43, Ptrend = 0.04) in never smokers and 1.35 (95%CI, 0.79–2.30, Ptrend = 0.04) in men. In haplotype analysis, the 1G-6A-82A-1082G haplotype was associated with higher risk of lung cancer among never smokers, with the AOR of 3.65 (95%CI, 1.62–8.20) when compared with the most common 1G-5A-82A-1082A haplotype. In conclusion, the combined MMP genotypes and associated haplotypes may be associated with higher risk of lung cancer, particularly among never smokers and men.

Keywords: AOR, adjusted odds ratio; CI, confidence interval; MMP, matrix metalloproteinases

Journal Article.  4548 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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