MMP7 and MMP8 genetic polymorphisms in bladder cancer patients

Abstract

IntroductionBreakdown of the extracellular matrix by matrix metalloproteinases (MMPs), as we know, is one of mechanisms involved and required in tumor invasion. MMP7 is a negative prognostic factor of various malignances, while MMP8 exhibits an inhibitory effect on tumorigenesis and metastasis. We evaluated the potential association of functional polymorphisms in the promoter of the MMP7 (rs11568818) and MMP8 (rs11225395) genes and bladder cancer (BCa) risk.Materials and methodsThe study included 241 BCa cases and 199 healthy population controls that were collected at the First Department of Urology, Medical University (Łódź, Poland) and at the Nofer Institute of Occupational Medicine (Łódź, Poland). Genomic DNA samples were isolated from venous blood and genetic polymorphisms were analyzed by real–time polymerase chain reaction using TaqMan fluorescent probes. Associations between genotype and allele status were estimated by logistic regression models adjusted for classic risk factors (e.g. age, gender and cigarette smoking).ResultsMMP7 and MMP8 genotypes were distributed similarly in BCa patients and in controls and at least one variant allele was not associated with BCa cancer risk (OR, 0.91; 95% CI, 0.60–1.39; p = 0.662 for MMP7 and OR, 0.96; 95% CI, 0.63–1.46; p = 0.836 for MMP8). We observed higher prevalence of MMP7 GG genotypes among BCa patients than in controls (OR, 1.54; 95% CI, 0.93–2.55; p = 0.093). Additionally, genetic polymorphisms in the MMP7 and MMP8 were not associated with the tumor grade or stage.ConclusionsOur results suggest that genetic variations in two genes encoding members of the MMP7 and MMP8 are not associated with a risk of BCa in the Caucasian population.

Functional polymorphisms in the matrix metalloproteinase genes and their association with bladder cancer risk and recurrence: A mini‐review

“…also reported an association between genetic polymorphisms in the MMP2 ( rs2285053 ), MMP7 ( rs11568818 ) and MMP8 genes ( rs11225395 ), and no association of genetic polymorphism in the MMP3 gene ( rs520540 ) with BC risk . Our study confirmed no association of genetic polymorphisms in the MMP2 ( rs243865 ), MMP7 ( rs11568818 ), MMP8 ( rs11225395 ), MMP9 ( rs3918242 ) and MMP12 genes ( rs2276109 ) with BC risk in Caucasian population …”

“…and Wieczorek et al . showed that MMP1 ( rs1799750 ) is significantly associated with BC risk, namely the 2G2G genotype with OR 2.79 (95% CI 1.53–5.60), 2 G2G genotype with OR 3.04 (95% CI 1.71–5.39) and 2G1G + 1G1G genotype with OR 0.62 (95% CI 0.39–0.98), respectively …”

Analysis of the Association of Matrix Metalloproteinase-1 Gene Promoter (rs1799750) Polymorphism and Risk of Ovarian Cancer

“…17Y19 It has been demonstrated that polymorphisms of some MMPs were strongly associated with a risk of cancer, such as prostate cancer, 20 breast cancer, 21,22 lung cancer, 23,24 and bladder cancer. 25,26 It has been reported that the matrix metalloproteinase-1 (MMP1) promoter j1607Ybase pair (bp) polymorphism was a negative prognostic parameter in patients with ovarian cancer. 27 The association between the MMP1 promoter j1607-bp polymorphism and ovarian cancer has been extensively investigated.…”

MMP1, 2, 3, 7, and 9 Gene Polymorphisms and Urinary Cancer Risk: A Meta-Analysis

“…We also found only one Chinese article in the WanFang database. As a result, 12 case-control articles were included in our meta-analysis: (Hirata et al, 2004;Zhong et al, 2005;Kader et al, 2006;Albayrak et al, 2007;Piccoli et al, 2007;Tasci et al, 2008;Tsuchiya et al, 2009;Srivastava et al, 2010aSrivastava et al, , 2010bWieczorek et al, 2013Wieczorek et al, , 2014Srivastava et al, 2013a) (Fig. 1).…”

“…A quantitative synthesis to accumulate data from different studies is needed to provide better evidence on these associations. Here, in this report, we performed a meta-analysis of 12 publications to estimate the effect of eight polymorphisms: MMP1 -1607 1G/2G (Hirata et al, 2004;Kader et al, 2006;Albayrak et al, 2007;Piccoli et al, 2007;Tasci et al, 2008;Tsuchiya et al, 2009;Srivastava et al, 2010a;Wieczorek et al, 2013), MMP2 -1306 C/T (Zhong et al, 2005;Kader et al, 2006;Srivastava et al, 2013a;Wieczorek et al, 2013), MMP3 (45E/K) G/A (Kader et al, 2006;Srivastava et al, 2010b), MMP7 -181 A/G (Srivastava et al, 2010a;Wieczorek et al, 2014), MMP9 -1562 C/T (Zhong et al, 2005;Kader et al, 2006;Wieczorek et al, 2013), MMP9 (279R/Q) A/G (Kader et al, 2006;Tasci et al, 2008;Srivastava et al, 2010b), and MMP9 (574R/P) T/C (Kader et al, 2006;Srivastava et al, 2010b), MMP9 (668Q/R) A/G (Kader et al, 2006;Srivastava et al, 2010b) on urinary cancer risk.…”