Mutagenesis Advance Access published online on October 20, 2009
Mutagenesis, doi:10.1093/mutage/gep041
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Polymorphisms in the promoter regions of matrix metalloproteinases 1 and 3 and cancer risk: a meta-analysis of 50 case–control studies
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, People's Republic of China 1Department of Biochemistry and Molecular Biology, West China Medical Center, Sichuan University, Chengdu 610041, People's Republic of China
Matrix metalloproteinase (MMP) 1 and MMP3 are enzymes that degrade the extracellular matrix and have been implicated to play an important role in cancer development. Many studies have been carried out on the association between polymorphisms of MMP1 –1607 1G>2G and MMP3 –1171 5A>6A and cancer risk. However, results from these studies remain inconclusive. Here, we performed a meta-analysis of >38 000 subjects to better assess the purported associations. For MMP1, –1607 2G/2G genotype carriers were found to have an increased risk of colorectal cancer [2G/2G versus 2G/1G + 1G/1G, odds ratio (OR) = 1.48, 95% confidence interval (CI) (1.26–1.74), Pheterogeneity = 0.066, I2 = 49.3%], head and neck cancer [2G/2G versus 2G/1G + 1G/1G, OR = 1.61, 95% CI (1.26–2.07), Pheterogeneity = 0.002, I2 = 64.7%] and renal cancer [2G/2G versus 2G/1G + 1G/1G, OR = 1.82, 95% CI (1.38–2.39), Pheterogeneity = 0.589, I2 = 0.0%] risk. For MMP3, no association was found between –1171 5A>6A polymorphism and cancer risk in the overall group [6A versus 5A, OR = 1.00, 95% CI (0.95–1.05), Pheterogeneity = 0.124, I2 = 24.9%] and individual cancer subgroups, but stratified analysis by smoking status showed that this polymorphism had different effects on smokers and non-smokers under recessive genetic model. In summary, our study suggests that MMP1 –1607 2G may be associated with an increased cancer risk for certain types of cancers, MMP3 –1171 5A>6A may not be a major risk factor for cancer, but it may be modified by certain environmental factors. Future studies with larger sample sizes are warranted to further evaluate these associations in more detail.
* To whom correspondence should be addressed. Tel: +86 216 564 3404; Fax: +86 216 564 3404; Email: longyu{at}fudan.edu.cn
These authors contributed equally to this work.
Received on June 24, 2009; revised on August 26, 2009; accepted on September 14, 2009.