Carcinogenesis Advance Access originally published online on November 25, 2005
Carcinogenesis 2006 27(5):1024-1029; doi:10.1093/carcin/bgi283
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Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cancer
1 Department of Environmental Health, 2 Department of Biostatistics, Harvard School of Public Health, 3 Thoracic Surgery Unit, Department of Surgery, 4 Department of Hematology-Oncology, and 5 Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
* To whom correspondence should be addressed at: Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. Tel: +1 617 432 3323; Fax: +1 617 432 6981; Email: dchristi{at}hsph.harvard.edu
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.
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