1. Polymorphisms in MMP-14 and MMP-2 genes and ovarian cancer survival
- Author
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Angela A.G. van Tilborg, William J. Brands, Brenda M. Pijlman, Dorry Boll, M. Caroline Vos, Toin H. van Kuppevelt, Hans van der Putten, Leon F.A.G. Massuger, Anneke A. M. van der Wurff, and Dennis van Hamont
- Subjects
0301 basic medicine ,Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Genotype ,Polymorphism, Single Nucleotide ,Disease-Free Survival ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,Gene Frequency ,Internal medicine ,Genetics ,medicine ,Matrix Metalloproteinase 14 ,Coding region ,Humans ,Genetic Predisposition to Disease ,Allele frequency ,Ovarian Neoplasms ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,business.industry ,Hazard ratio ,Promoter ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,Bonferroni correction ,Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] ,030220 oncology & carcinogenesis ,symbols ,Immunohistochemistry ,Matrix Metalloproteinase 2 ,Female ,business ,Ovarian cancer - Abstract
BACKGROUND Functional polymorphisms in matrix metalloproteinases can increase or decrease the risk of cancer. This study focused on ovarian cancer and investigated how polymorphisms in the coding region of MMP-14 and the promoter region of MMP-2 are related to clinical characteristics including survival. METHODS In 144 patients with ovarian tumours from a Caucasian population, polymorphisms of MMP-14 (+7096 and +6767) and MMP-2 (-735 and -1306) were analysed. These results were then correlated to the immunohistochemical expression of MMP-14 and MMP-2 and clinical characteristics. RESULTS In these patients, the MMP-14 +7096 polymorphism showed only TT genotype, in sharp contrast to the described MAF (minimal allele frequency) C of 27%. The MMP-14 +6767 G>A polymorphism was found to have a hazard ratio of 2.09 (CI 1.00-4.35, p 0.046) for recurrence-free survival in advanced-stage patients. However, this significance disappeared after Bonferroni correction for multiple testing. No other correlations between MMP-14 and MMP-2 polymorphisms, immunohistochemistry and clinical characteristics were found, except between the MMP-2 -1306 polymorphism and differentiation grade, with a Spearman correlation coefficient of -0.19, p 0.064. CONCLUSIONS In ovarian cancer, the MMP-14 +6767 G>A polymorphism in the coding region seems to improve recurrence-free survival with a hazard ratio of 2.09 (CI 1.00-4.35, p 0.046). However, as this significance disappeared after correction for multiple testing, there is a need for further research on the functional effect of this change in the MMP-14 gene with larger patient sample sizes.
- Published
- 2019