Gene Polymorphisms Of Matrix Metalloproteinase-2,7: Study Of Their Effect Upon The Occurrence And Lymph Node Metastasis Of Cervical Cancer In Shanxi

Purpose: Investigating possible interaction between gene polymorphisms of MMP-2,7 and their effect on the occurrence and lymph metastasis of cervical cancer in Shanxi province of China.Methods: A retrospective case-control study design was applied for the present study. The case group included 212 paraffin embedded the early cervical tissue samples (48 cases with lymph metastasis and 164 cases without metastasis) and 225 peripheral blood samples (39 cases with lymph metastasis and 186 cases without metastasis) from patients with the early stage of cervical cancer. The control group consisted of 172 normal paraffin embedded cervical tissue samples and 170 of peripheral blood samples from healthy women. Both groups of samples were collected from Shanxi province. Using genomic DNA as templates, we employed polymerase chain reaction- restriction fragment length polymorphism (PCR- RFLP) to analyze the genotype distribution and allele frequency of MMP-2-735C/T and MMP-7 -181A/G ;used Tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) to analyze the genotype distribution and allele frequency of MMP-2 -1306C/T. Chi-square test ( 2 test) was used for statistical comparison of genotype distribution and allele frequency between the case group and the control group as well as between the group with metastasis and the group without metastasis. Odds ratio (OR) and 95% confidence interval (CI) indicated relative risk.The effect modified model was used to evaluate the gene-gene interaction of gene polymorphisms of MMP-2 -735C/T,-1306C/T and MMP-7-181A/G .Results: 1. MMP-2-735C/T gene polymorphisms include three genotypes: CC,CT and TT.â‘ For MMP-2-735 CC,CT, TT distribution and C, T allele frequency in peripheral blood samples, there is no statistical significance (P>0.05) between the case group and the control group as well as between the group with lymph metastasis and the group without metastasis.â‘¡For MMP-2-735 genotype distribution in tissue samples, there is also no statistical significance (P>0.05) between the case group and the control group as well as between the group with lymph metastasis and the group without metastasis. But for MMP-2-735 allele frequency Genotype ,there is statistical significance (P<0.05) between the case group and the control group;Compared to T allele, C allele increase the risk of cervical cancer for 1.542 folds. 2.For MMP-2 -1306C/T gene polymorphisms;â‘ Including genotype distribution and allele frequency in peripheral blood samples, there is statistical significance (P<0.05) between the case group and the control group. The risk of genotype CC and C allele for cervical cancer is 2.239 and 1.563, respectively. Compared to genotype (T/T+C/T), genotype CC increase the risk of lymph node metastasis for 2 folds (OR=2.388 , 95% CI=1.101-5.182).â‘¡In tissue samples, there is also statistical significance (P<0.05) between the case group and the control group as well as between the group with lymph metastasis and the group without metastasis. The risk of genotype CC and C allele for cervical cancer is 2.543 and 1.593, respectively. Compared to genotype (T/T+C/T), genotype CC increase the risk of lymph node metastasis for 2.568 folds. 3. MMP-7 -181A/G gene polymorphisms include three genotypes: AA,AG and GG.â‘ For MMP-7 -181 AA,AG, GG distribution and A, G allele frequency in peripheral blood samples, there is statistical significance (P<0.05) between the case group and the control group as well as between the group with lymph metastasis and the group without metastasis. The risk of genotype GG and G allele for cervical cancer is 3.283 and 1.480, respectively. Compared to genotype AA, genotype GG increase the risk of lymph node metastasis for 3.936 folds.â‘¡In tissue samples, there is also statistical significance (P<0.05) between the case group and the control group as well as between the group with lymph metastasis and the group without metastasis. The risk of genotype AG,GG and G allele for cervical cancer is 1.582,3.574 and 1.692, respectively. Compared to genotype AA, genotype GG increase the risk of lymph node metastasis for 4.629 folds. 4. There is interaction between gene polymorphisms of MMP-2 -735C/T,-1306C/T and MMP-7-181A/G in the occurrence of cervical cancer by using effect modified model, respectively.Conclusions: (1) In tissue samples, People with C allele at MMP-2 -735C/T site may have a higher risk for the occurrence of cervical cancer. (2) In both peripheral blood and tissue samples,People with genotype CC and C allele at MMP-2 -1306 C/T site may have a higher risk for the occurrence and lymph metastasis of cervical cancer. (3) In peripheral blood samples, People with genotype GG and G allele at MMP-7-181 A/G site may have a higher risk for the occurrence of cervical cancer;But in tissue samples, genotype AG,GG and G allele could enhance the occurrence of cervical cancer;People with genotype GG may have a higher risk for the lymph metastasis of cervical cancer. (4) In cervical cancer tissue, genotype MMP-2-1306CC and MMP-7-181 GG may induced the metastasis of cancer cells by changing the micro-environment. (5) The SNP sites of MMP-2-735C/T and MMP-2-1306C/T may be in cooperation with MMP-7-181A/G polymorphism to promote the incidence of cervical cancer ,respectively.Taken together, the study points out MMP-2 -735C/T,-1306 C/T and MMP-7-181 A/G gene polymorphisms could be used for screening population with high risk of occurrence and metastasis of cervical cancer, which will provide clues for prediction, primary prevention and therapy of cervical cancer.