Abstract

Background: Lung cancer is the most common cancer with 2,206,771 new cases in 2020 in worldwide. MMP9 is a member of matrix metalloproteinase family that is also known as gelatinase B or IV type collagenase (92KD). MMP9 through degrading of Extracellular Matrix (ECM) and releasing of growth factors has fundamental role in the tumorigenesis process. The C -1562 T SNP in the MMP9 promoter increases MMP9 expression and susceptibility to lung cancer. Then, the aim of this present case-control study was to investigate whether genetic variations of the MMP9 gene may constitute markers for lung cancer risk in males and in positive family history people in Iran. Methods: This is a case-control study including 120 lung cancer patients and 100 healthy controls. Polymorphism in the C -1562 T region was genotyped by PCR-RFLP assay. Odds Ratio (ORs) and 95% Confidence Intervals (CIs) were estimated by chi-square test from comparison of genotypes between lung cancer patients and healthy controls, using SPSS version 26.0. T-test and Image J software was also used. Results: The distribution of C-1562T genotype was significantly associated with the risk of lung cancer (Odds Ratio [OR] = 2.56, 95% Confidence Interval [CI] = 0.06-23.82). The further stratification analyses shown that males and patients with positive family history may increase risk of lung cancer. Conclusion: Our results indicated that the MMP9 C -1562 T polymorphism affects risk of lung cancer. In addition, men with T allele (OR = 3.94, CI = 1.47-10`.55) and patients with TT genotype and family history (OR = 2.18, CI = 1.03-4.59) exposure to higher risk of lung cancer.

Highlights

  • Carcinogenesis is a complex process in which cells undergo genetic and epigenetic changes

  • Our results indicated that the MMP9 C -1562 T polymorphism affects risk of lung cancer

  • We examined the C -1562 T polymorphism of MMP9 gene promoter by PCR-RFLP in lung cancer patients and controls (Figure 5) and verified digestion PCR-RFLP products by Image J software (Figure 7)

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Summary

Introduction

Carcinogenesis is a complex process in which cells undergo genetic and epigenetic changes. Matrix metalloproteinases are multifunctional proteases that proteolyze Extracellular Matrix (ECM) components with subsequent release of bioactive components and proteins [2,3]. They play an important role in chemokine processing They change the mode of activity of other proteases. MMP9 through degrading of Extracellular Matrix (ECM) and releasing of growth factors has fundamental role in the tumorigenesis process. The aim of this present case-control study was to investigate whether genetic variations of the MMP9 gene may constitute markers for lung cancer risk in males and in positive family history people in Iran

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