Objective: Polymorphisms of death receptor 4 (DR4) might impair the apoptotic signal transduction and lead to dysregulation of the homeostasis between cell survival and cell death, promoting tumor development and progression.
Methods: We performed an analysis of known DR4 polymorphisms, namely G442A, C626G, and A1322G, in germ line DNA of 97 ovarian cancer patients and controls as well as in established ovarian cancer cell lines.
Results: Patient and matched control populations were not differing significantly in case of G442A (P = 0.736) and C626G alterations (P = 0.699). For the A1322G transversion, we generated population data for the first time and could find a rate of 19% heterozygotes and 3% homozygotes. Again, we could not detect any significant difference between patients and controls (P = 0.326).
Conclusion: To summarize, alterations of the DR4 gene do not lead to clinically relevant ovarian cancer predisposition and are therefore most unlikely to contribute to familial ovarian cancer.