The Relationship between Matrix Metalloproteinase Gene Polymorphisms and Tumor Type, Tumor Size, and Metastasis in Women with Breast Cancer in Central Iran

Background: Matrix metalloproteinases-۲ and -۹ play important roles in the development of breast cancer by hydrolyzing the extracellular matrix. Since −۱۳۰۶C/T and −۱۵۶۲C/T polymorphisms are located at the promoter regions of the matrix metalloproteinase- ۲ and -۹ genes, respectively, C to T substitution may affect promoter activity and impact the rate of extracellular matrix degradation and cancerous cell proliferation. Therefore, we aimed to determine the genotype and allele frequencies of these polymorphisms in Iranian healthy women and women with breast cancer. We have also examined the correlation of genotypes with clinicopathological parameters such as tumor type, tumor size, and metastasis to lymph nodes.Methods: This case-control study enrolled ۲۰۰ women with breast cancer and ۲۰۰ age-matched healthy women. DNA was extracted, and we determined the genotype and allele frequencies of −۱۳۰۶C/T matrix metalloproteinase-۲ and −۱۵۶۲C/T matrix metalloproteinase-۹ polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method. Additionally, tumor size (۲۰ mm), tumor type (ductal/non-ductal), and metastasis (yes/no) were determined.Results: Genotype and allele frequencies of the −۱۳۰۶C/T matrix metalloproteinase- ۲ polymorphism showed no significant association with the occurrence of breast cancer. Genotype and allele distribution differed in the −۱۵۶۲C/T matrix metalloproteinase- ۹ polymorphism and indicated a ۴.۸۳-fold increase in the risk of breast cancer for T allele carriers. There was no likelihood of any interaction found between the two polymorphisms and susceptibility to breast cancer. In addition, the −۱۵۶۲C/T matrix metalloproteinase-۹ T allele showed an association with metastasis to lymph nodes but we observed no association between the −۱۳۰۶C/T matrix metalloproteinase- ۲ polymorphism and clinicopathological features.Conclusion: The ‒۱۵۶۲C/T matrix metalloproteinase-۹ polymorphism is involved in the pathogenesis of breast cancer in Iranian women. The T allele may increase the risk of disease.