Polymorphisms in MMP-14 and MMP-2 genes and ovarian cancer survival

Article type: Research Article

Authors: Vos, M. Caroline^{a; *} | van Tilborg, Angela^b | Brands, William J.^c | Boll, Dorry^a | van Hamont, Dennis^d | van der Putten, Hans^e | Pijlman, Brenda^f | van der Wurff, Anneke A.M.^c | van Kuppevelt, Toin H.^g | Massuger, Leon F.A.G.^h

Affiliations: [a] Department of Obstetrics and Gynaecology, Elisabeth-Tweesteden Hospital, 5000 LC Tilburg, the Netherlands | [b] Department of Obstetrics and Gynaecology and Department of Pathology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, the Netherlands | [c] Department of Pathology, Elisabeth-Tweesteden Hospital, 5000 LC Tilburg, the Netherlands | [d] Department of Obstetrics and Gynaecology, Amphia Ziekenhuis, Breda, the Netherlands | [e] Department of Obstetrics and Gynaecology, Catharina Hospital, Eindhoven, the Netherlands | [f] Department of Obstetrics and Gynaecology, Jeroen Bosch Ziekenhuis, s-Hertogenbosch, the Netherlands | [g] Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, 6500 HB Nijmegen, the Netherlands | [h] Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, the Netherlands

Correspondence: [*] Corresponding author: M.C. Vos, Department of Obstetrics and Gynaecology, Elisabeth-Tweesteden Hospital, PO Box 90151, 5000 LC Tilburg, the Netherlands. E-mail: [email protected].

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.

Keywords: MMP-14, MMP-2, polymorphisms, ovarian cancer

DOI: 10.3233/CBM-181826

Journal: Cancer Biomarkers, vol. 25, no. 3, pp. 233-241, 2019