Activities and polymorphisms of MMP-2 and MMP-9, smoking, diabetes and risk of prostate cancer
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ORIGINAL ARTICLE
Activities and polymorphisms of MMP‑2 and MMP‑9, smoking, diabetes and risk of prostate cancer Amir Kiani1 · Marjan Kamankesh2 · Asad Vaisi‑Raygani2 · Mahmoud‑Reza Moradi1 · Maryam Tanhapour2 · Zohreh Rahimi3 · Saeed Elahi‑Rad1 · Fariborz Bahrehmand3 · Mahdieh Aliyari2 · Faranak Aghaz2 · Hadi Mozafari2 · Nayebali Rezvani2 · Lida Haghnazari2 · Tayebeh Pourmotabbed4 Received: 6 April 2020 / Accepted: 31 October 2020 © Springer Nature B.V. 2020
Abstract 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. Keywords Matrix metalloproteinase (MMP) · Tissue inhibitors of metalloproteinases (TIMPs) · Prostate cancer · Diabetes · Prostate-specific antigen and testosterone
Introduction Prostate cancer (PCa) is the second most prevalent cancer among males [1, 2]. While some types of prostate cancer grow slowly and may need minimal or even no treatment, other types are aggressive and can spread quickly. The most common sites of metastasis are liver, bladder, bones, lungs, brain and lymph nodes [3]. Although the specific mechanisms facilitating the invasive behaviors of PCa are unclear, tumor cell invasion and metastasis are known to be * Asad Vaisi‑Raygani [email protected] * Tayebeh Pourmotabbed [email protected]; [email protected] Extended author information available on the last page of the article
mediated, at least in
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