Genetische Risikofaktoren für das Ovarial- und Endometriumkarzinom bei Patientinnen mit Endometriose in einer deutschen Fall-Kontroll-Studie.

Background and aims: Currently, there does not exist any appropriate screening-programme for ovarian or endometrial cancer, partially caused by a low incidence of these diseases. One possibility to set about this problem is the definition of subpopulations with higher incidences on the basis of risk factors. Based on genome wide association studies, there could be identified several susceptibility loci with single nucleotide polymorphisms (SNPs) for each of the diseases on its own (endometriosis, ovarian and endometrial cancer). Whether there are overlapping genetic variations among patients with endometriosis and ovarian- and endometrial cancer, which would make a common molecular pathogenesis supposable, has not been researched sufficiently up to this date and is subject of this study. Methodes: In a hospital based, retrospective case control study, 59 single nucleotide polymorphisms, which were associated with ovarian cancer (21 SNPs), endometrial cancer (11 SNPs) or endometriosis (27 SNPs) in GWAS before, were genotyped using TaqMan® OpenArray™ analysis. The cases consisted of patients with endometriosis, and the controls were healthy individuals without endometriosis. A total of 869 women, 385 cases and 484 controls were analysed. Odds Ratios (OR) and P values were obtained using simple logistic regression models, as well as multiple logistic regression models with adjustment for clinical predictors. Results and observations: The test results show significant P values (p < 0.05) for six SNPs (rs10811661, rs10508881, rs12248560, rs7405776, rs757210, rs11651755) before correction for multiple testing. However, these values are insignificant after Bonferroni-Holm correction for multiple testing. In terms of endometriosis these SNPs have an OR < 1 that shows a decreasing risk. For rs11651755 in HNF1B there was found the lowest OR and lowest P value before and after correction for multiple testing (OR 0.67 (0.52;0.87), p < 0.01 respectively p = 0.13 after correction for multiple testing). Practical conclusions: The results of the conducted study can provide an indication of common genetic variations between endometriosis and ovarian cancer. As rs11651755 in HNF1B modified both, the risk of ovarian cancer and also the risk of endometriosis, HNF1B may be causally involved in a pathogenetic pathway leading from endometriosis to ovarian cancer. Concerning endometrial cancer, the results reflect the heterogeneous study situation.