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Carcinogenesis Advance Access published online on November 25, 2005
Carcinogenesis, doi:10.1093/carcin/bgi283
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received September 13, 2005
Revised October 26, 2005
Accepted November 20, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

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

Li Su 1 {dagger}, Wei Zhou 1 {dagger}, Kofi Asomaning 1, Xihong Lin 2, John C. Wain 3, Thomas J. Lynch 4, Geoffrey Liu 5, and David C. Christiani 6 *

1 Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts
2 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
3 Thoracic Surgery Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
4 Department of Hematology-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
5 Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts; Department of Hematology-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
6 Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts; Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

* To whom correspondence should be addressed.
David C. Christiani, E-mail: dchristi{at}hsph.harvard.edu


  Abstract

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 of subjects with 5+ variant alleles vs. zero variant allele of 1.31 (95% confidence interval, 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.

{dagger}Contributed equally to this work.
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