Dataset Information

Association of matrix metalloproteinase-3 -1171(5A>6A) polymorphism with cancer risk: a meta-analysis of 41 studies.

ABSTRACT:

Background and 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.

Methodology/principal findings

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%).

Conclusion

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.

SUBMITTER: Yang X

PROVIDER: S-EPMC3906197 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Association of matrix metalloproteinase-3 -1171(5A>6A) polymorphism with cancer risk: a meta-analysis of 41 studies.

Yang Xin X Hu Jing-Wen JW Qiu Man-Tang MT Li Ming M Yin Rong R Wang Jie J Xu Lin L Zhang Qin Q

PloS one 20140129 1

<h4>Background and objective</h4>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.<h4>Methodology/principal findings</h4>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 asses ...[more]

PMID: 24489939

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Project description:Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Background Remarkable progress has been made in understanding the genetic basis of dilated cardiomyopathy (DCM). Rare variants in >30 genes, some also involved in other cardiomyopathies, muscular dystrophy, or syndromic disease, perturb a diverse set of important myocardial proteins to produce a final DCM phenotype. Research objective The purpose of the present study was to determine the association between matrix metalloproteinase -3 (MMP-3) gene polymorphism - 1171 5A/6A (rs35068180) with myocardial dilation of ischemic and idiopathic origin. Materials and methods We studied 221 patients with with myocardial dilation of ischemic and idiopathic origin. Their average age was 55.30 ± 9.69 years. The group of patients with with myocardial dilation of ischemic origin consisted of 111 people, including 99 men (89.2%) and 12 women (10.8%). The average age of the subjects with myocardial dilation of ischemic origin was 51.73 ± 9.74 years, the age of the male subgroup was 51.00 ± 8.96 years, and the age of the female subgroup was 57.75 ± 3.71 years. A total of 110 patients with myocardial dilation of idiopathic origin were included in the study. There were 100 male patients (91.5%) and 10 female patients (8.5%). The average age of the studied patients with myocardial dilation of idiopathic origin was 58.68 ± 8.38 years, in men it was 58.29 ± 8.46 years, in women - 62.90 ± 6.29 years. The control group of subjects (121 persons) was represented by healthy people without diseases of the cardiovascular system. The average age of control subjects was 53.6 ± 4.8 years. We examined all patients in the main group using routine laboratory and instrumental methods, as well as coronary angiography. If myocarditis was suspected, we did an MRI of the heart. All patients underwent PCR to determine - 1171 5A/6A (rs35068180) polymorphism of the MMR gene. Results Patients with cardiomyopathies in the general group, regardless of the etiology of the disease, demonstrated statistically significant differences compared with the control group subjects. 6A allele (65.8% versus 59.3%, p = 0.044) and 6A / 6A genotype (42.1% versus 32.6%, p = 0.099) were significantly more frequent in patients with cardiomyopathies than in the control group. In addition, despite various etiological factors, the participation of the MMP-3 protein in the pathogenesis of these cardiomyopathies, probably, has a general tendency. Conclusion We have proved the predominance of the MMP-3 gene A allele in the cardiomyopathies group without taking into account the etiological factors of the disease development. In connection with a decrease in the activity of the transcription process in case of homozygous 6A allele, the level of stromelysin in arterial walls also decreases. This contributes to the activation of type 1 procollagenase, extracellular matrix deposition and cardiac muscle remodeling.

Project description:ContextThe exact factors that determine the biological behavior of odontogenic lesions have not been thoroughly established yet. The influence of the matrix metalloproteinases (MMPs) on the clinical behavior of these lesions was recently brought to light.AimsWe did a pioneer study to investigate the association of MMP9 (rs3918242 [-1562 C/T] and rs17576) and MMP2 (rs243865 [-1306 C/T] and rs865094) gene polymorphisms and aggressiveness of ameloblastomas, keratocystic odontogenic tumors (KCOT) and dentigerous cysts (DC).Settings and designA case-control study conducted in the Department of Oral Pathology and Microbiology, Government Dental College, Trivandrum and Human Molecular Genetics Laboratory, Rajiv Gandhi Institute of Biotechnology and Poojappura, Trivandrum, Kerala.Subjects and methodsDNA from the blood samples of histopathologically proven ameloblastoma (n = 15), KCOT (n = 11) and DC (n = 13) patients were extracted using standard protocols. Primers were designed based on the functionality and relevance for polymerase chain reaction (PCR). PCR products were analyzed by PCR-restriction fragment length polymorphism and sequencing.Statistical analysis usedChi-square analysis was done to assess the association of gene polymorphisms among the cases and controls.ResultsAmeloblastomas showed a higher frequency of mutant allele (T = 0.43; P = 0.05) of MMP9 rs3918242 (-1562C/T) compared to the control population. All the cases showed a statistically significant difference in the distribution of genotype (P = 0.046) and allele (P = 0.03; odds ratio [OR] = 2.06 [1.08-3.95]) frequency of MMP2 rs2438659 (-1306C/T). KCOT samples also showed a significant association in distribution of both genotype (P = 0.01) and allele (P = 0.01 with an OR at 3.42 [1.31-8.92]) frequency, on comparison with control population.ConclusionsMMP2 rs243865 polymorphism has a plausible role in increasing the aggressiveness of ameloblastomas and KCOT compared to that of the control population. Furthermore, MMP9 rs3918242 polymorphism may contribute to the aggressive behavior of ameloblastomas.

Dataset Information

Association of matrix metalloproteinase-3 -1171(5A>6A) polymorphism with cancer risk: a meta-analysis of 41 studies.

Background and objective

Methodology/principal findings

Conclusion

Publications

Association of matrix metalloproteinase-3 -1171(5A>6A) polymorphism with cancer risk: a meta-analysis of 41 studies.

Similar Datasets

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