title: Functional haplotypes in the promoter of matrix metalloproteinase-2 and lung cancer susceptibility.
abstract: 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.
authors.affiliation: Department of Etiology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Chunyuan
authors.initials: C
authors.lastname: Yu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Xiong
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012306:Risk; D012907:Smoking / Q000009:adverse effects
chemical_list: D020778:Matrix Metalloproteinase 2