Association of matrix metalloproteinase-3 -1171(5A>6A) polymorphism with cancer risk: a meta-analysis of 41 studies.
OBJECTIVE
Evidence has shown that matrix metalloproteinases-3 (MMP3) is important for cancer progression. Recent studies about the association between the -1171(5A>6A) polymorphism in MMP3 promoter region and cancer risk have yielded conflicting results.


RESULTS
We performed a meta-analysis of 41 studies including 11112 cases and 11091 controls to determine whether the -1171(5A>6A) polymorphism of MMP3 was associated with cancer risk. We assessed the strength of association and performed sub-group analyses by cancer types, ethnicity, smoking status, genotyping method, source of controls and sample size. The pooled results revealed that no significant association of the -1171(5A>6A) polymorphism with overall cancer risk in any of four models. Further sub-group analysis revealed that individuals with the 6A allele had lower risk of gastrointestinal cancer in two models: heterozygote comparison (6A/5A vs. 5A/5A: OR=0.74, 95%CI: 0.60-0.91; I(2)=1.9%), and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.77, 95%CI: 0.64-0.94; I(2)=29.0%). Additionally, the associations were significant in Asian populations for three models: homozygote comparison (6A/6A vs. 5A/5A, OR=0.68, 95%CI: 0.52-0.90; I(2)=26.7%), heterozygote comparison (6A/5A vs. 5A/5A: OR=0.75, 95%CI: 0.58-0.98; I(2)=0.0%), and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.69, 95%CI: 0.54-0.88; I(2)=0.5%). It was noteworthy that we had a contrary finding in non-smokers: the variant 6A/6A homozygote might statistically increase cancer risk compared with 6A/5A+5A/5A genotype (OR=1.92, 95%CI: 1.25-2.96; I(2)=72.7%).


CONCLUSIONS
This meta-analysis suggests that the -1171(5A>6A) polymorphism in MMP3 promoter region is not associated with overall cancer risk, but it may contribute to decreased cancer risk in Asian population when compared with Caucasian population and significantly reduce the risk of gastrointestinal cancer.
The First Clinical College of Nanjing Medical University, Nanjing, China ; Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China ; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
Xin
X
Yang
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China ; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
Jing-Wen
JW
Hu
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China ; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
Man-Tang
MT
Qiu
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China ; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
Ming
M
Li
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China ; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
Rong
R
Yin
Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China ; Department of Scientific Research, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Nanjing, China.
Jie
J
Wang
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China ; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
Lin
L
Xu
Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China ; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
Qin
Q
Zhang
D016022:Case-Control Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk
C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3