Matrix metalloproteinase family gene polymorphisms and lung cancer susceptibility: an updated meta-analysis

Abstract

Background: Many studies have investigated the association between matrix metalloproteinase polymorphisms and lung cancer susceptibility. However, the results are still controversial. To clarify these associations, we conducted a meta-analysis. Methods: A systematic search of studies was conducted in PubMed, Embase, and China National Knowledge Infrastructure. Overall and subgroup analysis stratified by ethnicity was conducted. OR with 95% CI was used to assess the strength of the association. Furthermore, false-positive report probability (FPRP) tests were also performed for associations obtained in this meta-analysis. Results: Twenty-four studies, including 10,099 cases and 9,395 controls, were analyzed. Nine polymorphisms were reported. For MMP1 -1607 1G/2G and MMP7 -181 A/G, increased lung cancer risk was found in Asians. For MMP2 -1306 C/T and MMP2 -735 C/T, decreased lung cancer risk was found in both "diverse populations" and Asians. For MMP9 -1562, C/T decreased lung cancer risk was found in both "diverse populations" and Caucasians. For MMP13 -77A/G, the A/G genotype decreased lung cancer risk in Asians. However, only associations between MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -735 C/T, and MMP7 -181 A/G and lung cancer risk were considered noteworthy according to FPRP tests. There was no association between MMP3 -1171 5A/6A, MMP9 R279Q, and MMP12 -82A/G and lung cancer risk.

MMP2 gene polymorphism and tumor susceptibility study

“…In contrast it was a protective factor for nasopharyngeal and laryngeal cancers (ENT), esophageal cancer, gastric cancer, head and neck cancer and lung cancer. This result is in general agreement with previously published studies [12][13][14] [15][16]. In a subgroup analysis for different ethnic groups, we found that the rs243865 variant was associated with reduced cancer risk in East Asian populations and was instead a risk factor in South Asian populations.…”

“…The results of a meta-analysis including 29 eligible studies showed that the rs243865 C/T genotype was associated with reduced cancer risk [9]. Another meta-analysis based on 24 studies published several years later prompted that the rs243865 C/T and rs2285053 C/T variants may reduce the risk of lung cancer [10].…”

The multifaceted roles of matrix metalloproteinases in lung cancer

“…( 34 , 127 , 139 , 145 )( Table 4 ). In addition, subgroup analyses by ethnicity identified significant association with LC risk in Asians, while ethnicity among Caucasian had no relationship with LC susceptibility ( 34 ) ( Table 4 ), the results are consistent with the conclusion in another meta-analysis conducting on 24 studies with 10,099 LC cases and 9,395 controls ( 136 ). Possibly, genotypes varied between ethnic populations, therefore, there are differences of susceptibility to LC among various between ethnic populations.…”

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

“…The role of specific MMPs and ADAMs in breast [6,72,73], lung [74][75][76][77], prostate [78][79][80], and colorecta [81] cancer progression, invasion, and metastasis has been studied extensively [18,49,82]. MPs carry a multifaceted role in cancer and they can act as a pro-tumorigenic, anti-tumorigenic, or null factor [6], making it difficult to draw a general conclusion on the role of all MPs without considering all the parameters involved in the model of study such as the individual genomic profile, proteomic profile, and experimental conditions.…”