Activities and polymorphisms of MMP-2 and MMP-9, smoking, diabetes and risk of prostate cancer

• DOI: 10.1007/s11033-020-05968-5
• Publication Date: 2020-11-09T05:09:54Z
• Authors: Amir Kiani; Marjan Kamankesh; Asad Vaisi-Raygani; Mahmoud-Reza Moradi; Maryam Tanhapour; Zohreh Rahimi; Saeed Elahi-Rad; Fariborz Bahrehmand; Mahdieh Aliyari; Faranak Aghaz; Hadi Mozafari; Nayebali Rezvani; Lida Haghnazari; Tayebeh Pourmotabbed
• Keywords: Adult; Male; Tissue Inhibitor of Metalloproteinase-2; Polymorphism, Genetic; Tissue Inhibitor of Metalloproteinase-1; Genotype; Smoking; Prostatic Neoplasms; Comorbidity; Iran; Middle Aged; Prostate-Specific Antigen; 3. Good health; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Matrix Metalloproteinase 9; Risk Factors; Case-Control Studies; Diabetes Mellitus; Humans; Matrix Metalloproteinase 2; Testosterone

Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that are involved in tumor cell invasion and metastasis. The role of MMP-2 and -9 genetic polymorphism in different malignancies has been the subject of numerous studies. The present research has attempted to discover any positive correlation between MMP-2 and MMP-9 SNPs and prostate cancer (PCa) in patients with a history of either diabetes or smoking habits. 112 PCa-patients and 150 unrelated healthy-controls that matched for age and sex were selected for present case-control study. MMP-2 -1575G/A and MMP-9 -1562 C/T polymorphisms detected by PCR-RFLP, serum tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), testosterone, prostate-specific antigen (PSA), free-prostate-specific-antigen (fPSA), and fPSA/PSA levels were detected by ELISA and enzyme assay, respectively. MMP-2 and MMP-9 activities were measured by gelatin-zymography. Covariates were considered as age, status of cigarette smoking, and a possible history of diabetes mellitus (DM). The frequency of -1575 MMP-2 A/A + A/G and -1562 MMP-9 C/T + T/T genotypes were higher in PCa-patients with DM (74.3%,p = 0.003) and with smoking habits (72.5%,p = 0.005). These genotypes were associated with the increased risk of prostate cancer in smokers (3.52-folds) and in individuals with history of DM (4.34-folds). A significant positive association was found between level of TIMPs (TIMP -1 and TIMP-2) and BMI in PCa-patients and also between testosterone levels and MMP-9 activity in healthy control subjects. For the first time, this study demonstrated that activities of MMP-2 -1575G/A and MMP-9 -1562C/T variants in association with smoking and diabetes are considered significant risk factors for PCa.