SEGREGATION ANALYSIS OF EPITHELIAL OVARIAN-CANCER IN FINLAND

Epithelial ovarian cancer is known to aggregate in families. The domin antly inherited ovarian cancer predisposing genes, BRCA1, BRCA2 and ge nes involved in the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, have recently been identified. However, in the majority of families with more than one case of ovarian cancer, dominant inheritan ce cannot be recognized. We investigated familiar clustering of epithe lial ovarian cancer in a population-based sample of 663 Finnish ovaria n cancer patients. A segregation analysis with the POINTER software wa s conducted on the 937 nuclear families from these 663 pedigrees. The major gene model was favoured, and the sporadic and multifactorial mod els were strongly rejected. In the studied population, the best fittin g model was a recessive mode of inheritance, and 8% of ovarian cancer patients were estimated to be homozygous for the deleterious genotype. This evidence for recessively inherited ovarian cancer predisposition should be interpreted cautiously, as the analysis is subject to certa in errors, which are discussed in the article. Results of this analysi s, however, strongly emphasize the role of genetic factors in all fami lial aggregation of epithelial ovarian cancer.