Segregation analysis of epithelial ovarian cancer in Finland

• Published in: British journal of cancer Vol. 77; no. 9; pp. 1537 - 1541
• Main Authors: Auranen, A, Iselius, L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.1998; Nature Publishing Group
• Subjects: Adult; Age Distribution; Aged; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma - epidemiology; Carcinoma - genetics; Drug Resistance; Epidemiology; Female; Female genital diseases; Finland - epidemiology; Genes, BRCA1 - genetics; Genetic Markers - genetics; Gynecology. Andrology. Obstetrics; Humans; Male; Medical sciences; Middle Aged; Models, Genetic; Molecular Medicine; Oncology; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - genetics; Phenotype; Tumors; Europe; Finland; Human; Statistical analysis; Carcinoma; Family study; Malignant tumor; Hereditary; Female genital diseases; Genetic disease; Ovarian diseases; Segregation analysis; Ovary; Epidemiologic genetics; Predisposition; Recessive character; Public health
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.1998.252

Epithelial ovarian cancer is known to aggregate in families. The dominantly inherited ovarian cancer predisposing genes, BRCA1, BRCA2 and genes 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 inheritance cannot be recognized. We investigated familial clustering of epithelial ovarian cancer in a population-based sample of 663 Finnish ovarian cancer patients. A segregation analysis with the POINTER software was conducted on the 937 nuclear families from these 663 pedigrees. The major gene model was favoured, and the sporadic and multifactorial models were strongly rejected. In the studied population, the best fitting 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 certain errors, which are discussed in the article. Results of this analysis, however, strongly emphasize the role of genetic factors in all familial aggregation of epithelial ovarian cancer.