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.

基质金属蛋白酶（MMPs）是一组锌依赖性酶，参与肿瘤细胞的侵袭和转移。MMP-2和-9基因多态性在不同恶性肿瘤中的作用已成为众多研究的主题。本研究试图发现患有糖尿病或吸烟习惯的患者中MMP-2和MMP-9 SNP与前列腺癌（PCa）之间存在任何正相关。选择112例PCa患者和150例年龄和性别相匹配的无关健康对照者进行本病例对照研究。PCR-RFLP检测到MMP-2 -1575G / A和MMP-9 -1562 C / T多态性，血清金属蛋白酶抑制剂（TIMP-1和TIMP-2），睾丸激素，前列腺特异性抗原（PSA），游离分别通过ELISA和酶法检测前列腺特异性抗原（fPSA）和fPSA / PSA水平。MMP-2和MMP-9活性通过明胶酶谱法测定。协变量被认为是年龄，吸烟状况以及可能的糖尿病史（DM）。PCa DM患者（DM）（-74.3％，p = 0.003）和吸烟习惯（-154.3 MMP-2 A / A + A / G和-1562 MMP-9 C / T + T / T基因型的频率更高） 72.5％，p = 0.005）。这些基因型与吸烟者（3.52倍）和有DM史（4.34倍）的个体患前列腺癌的风险增加相关。在PCa患者中，TIMP（TIMP -1和TIMP-2）与BMI的水平之间存在显着正相关，在健康对照者中，睾丸激素水平与MMP-9活性之间也存在显着正相关。首次，