Matrix metalloproteinase 1, 3, and 9 polymorphisms and esophageal squamous cell carcinoma risk.
BACKGROUND
Matrix metalloproteinases (MMPs) are multifunctional zinc-dependent proteinases that play a fundamental role in the pathogenesis of tumors. We have analyzed the association between 3 single-nucleotide polymorphisms (SNPs; MMP1 -1607 1G/2G, MMP3 -1612 5A/6A, and MMP9 -1562 C/T) and the risk of esophageal squamous cell carcinoma (ESCC).


METHODS
We investigated these 3 SNPs in 132 patients and 132 controls using polymerase chain reaction-restriction fragment length polymorphism methods. The MMP1 and MMP3 genes are located on the same chromosome. Haplotype analysis was performed to study the combined effect of the linked MMP polymorphisms on ESCC risk.


RESULTS
The MMP1 and MMP9 promoter polymorphisms were not associated with ESCC risk, while the MMP3 -1612 5A/6A polymorphism was significantly associated with susceptibility to ESCC. Patients carrying the 5A allele had a significantly higher risk for developing ESCC compared with individuals carrying the 6A allele (OR=1.93; 95% CI 1.34-2.77; p<0.01). The 2G-5A and 1G-5A haplotypes were associated with a significantly increased risk of ESCC as compared with the 2G-6A haplotype (OR=2.04, 95% CI 1.37-3.04 and OR=3.65, 95% CI 1.26-10.55, respectively).


CONCLUSIONS
These findings implicate this MMP3 polymorphism as a contributor to ESCC susceptibility.
School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China (mainland).
Xuan
X
Guan
Primary Care Center, Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (mainland).
Xiang
X
Wang
Nursing Department, Leshan Vocational, Leshan, Sichuan, China (mainland).
Hao
H
Luo
Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China (mainland).
Jing
J
Wu
School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China (mainland).
Xiao
X
Zhang
Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China (mainland).
Jin
J
Wu
D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1