Background. The FANCD2 gene plays an important role in the homologous DNA repair pathway (HR), also called Fanconi anemia pathway (FA), however little is known of its role in ovarian cancer development and prognosis. We aimed to analyse mutations and polymorphisms in the FANCD2 gene in ovarian cancer patients. Additionally we evaluated p.Pro714Leu polymorphic variants of the FANCD2 gene with respect to their clinical importance.

Methods. We genotyped 198 ovarian cancer patients from central Poland with the use of PCR-SSCP and direct sequ­encing methods. Analysis was performed on part of the coding sequence of FANCD2 gene (exons 8–13, 19 and 23), with the fosforylation and monoubiquitatin sites of FANCD2 protein. The prognostic/predictive significance of p.Pro714Leu polymorphic variants was determined in a group of 111 ovarian cancer patients (FIGO stage II–IV) for which complete clinical data were available. The analysis was performed with the use of univariate and multivariate statistical methods for ovarian cancer patients treated with chemotherapy.

Results. We found two novel, unpublished mutations of (c.990-24 T> G (0.5%) and c.1129 A> C, p.Lys351Gln (0.5%)) within the analysed sequence of the FANCD2 gene. The presence of four previously described polymorphic variants was also confirmed: rs17032283 (5.5%), rs9809061 (17.5%), rs3864017 (16.5%), rs55856815 (5.5%).

Statistical analysis revealed no relationship between the p.Pro714Leu polymorphism and response to chemotherapy (CR and PS), the risk of death (OS) and the risk of recurrence (DFS) in any of the analysed group of patients.

Conclusions. Our results show novel substitution identified in single ovarian cancer patients for the first time. However the low incidence of mutations (1%) in the analysed sequence suggests that FANCD2 alterations are not the primary mechanism for disrupting the function of the encoded FANCD2 protein in ovarian cancer patients. Furthermore we found that the p.Pro714Leu polymorphic variants were not associated with clinical endpoints in any of analysed groups.