Journal Article

Functional haplotypes in the promoter of <i>matrix metalloproteinase-2</i> and lung cancer susceptibility

Yifeng Zhou, Chunyuan Yu, Xiaoping Miao, Yonggang Wang, Wen Tan, Tong Sun, Xuemei Zhang, Ping Xiong and Dongxin Lin

in Carcinogenesis

Volume 26, issue 6, pages 1117-1121
Published in print June 2005 | ISSN: 0143-3334
Published online February 2005 | e-ISSN: 1460-2180 | DOI:
Functional haplotypes in the promoter of matrix metalloproteinase-2 and lung cancer susceptibility

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Matrix metalloproteinase-2 (MMP-2) plays important roles in cancer initiation and progression. Our previous studies revealed that the −1306C→T and −735C→T polymorphisms in MMP2 promoter significantly influence transcriptional activity and their genotypes and haplotypes are associated with susceptibility to several cancers. This case–control study examined the contribution of these two polymorphisms to the risk of developing lung cancer. MMP2 genotypes and haplotypes were determined in 770 cases and 777 controls and the associations with risk of lung cancer were estimated by logistic regression. We observed a 2-fold [odds ratio (OR), 2.12; 95% confidence interval (CI), 1.64–2.72] or 1.6-fold (OR, 1.57; 95% CI, 1.27–1.95) excess risk of developing lung cancer for the −1306CC or −735CC genotype carriers compared with non-carriers, respectively. A greater risk of lung cancer was associated with the C−1306–C−735 haplotype (OR, 5.01; 95% CI, 2.57–9.78) compared with the T−1306–T−735 haplotype, suggesting a synergic effect of these two polymorphisms. Furthermore, a greater than additive joint effect of the polymorphisms and smoking increased an even higher risk of lung cancer. The OR for smokers with the C−1306–C−735 haplotype was 6.24 (95% CI, 4.51–8.64), which was significantly higher than that (OR, 4.10; 95% CI, 2.89–5.81) of smokers with the T−1306 or T−735-containing haplotypes (P < 0.001). These results are consistent with our previous findings and further support the hypothesis that gain-of-function of MMP2 resulting from genetic polymorphisms plays an important role in human carcinogenesis.

Keywords: CI, confidence interval; MMP-2, matrix metalloproteinase-2; OR, odds ratio; SCC, squamous cell carcinoma; SNP, single nucleotide polymorphism.

Journal Article.  4209 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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