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

• Published in: Molecular biology reports 2020-12, Vol.47 (12), p.9373-9383
• Main Authors: Kiani, Amir, Kamankesh, Marjan, Vaisi-Raygani, Asad, Moradi, Mahmoud-Reza, Tanhapour, Maryam, Rahimi, Zohreh, Elahi-Rad, Saeed, Bahrehmand, Fariborz, Aliyari, Mahdieh, Aghaz, Faranak, Mozafari, Hadi, Rezvani, Nayebali, Haghnazari, Lida, Pourmotabbed, Tayebeh
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Antigens; Biomedical and Life Sciences; Cigarette smoking; Diabetes; Diabetes mellitus; Enzyme-linked immunosorbent assay; Gelatin; Gelatinase A; Gelatinase B; Gene polymorphism; Histology; Life Sciences; Matrix metalloproteinase; Metastases; Morphology; Original Article; Prostate cancer; Prostate-specific antigen; Risk factors; Single-nucleotide polymorphism; Smoking; Testosterone; Tissue inhibitor of metalloproteinase 1; Tissue inhibitor of metalloproteinase 2
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-020-05968-5

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.