title: Complex segregation analysis of pedigrees from the Gilda Radner Familial Ovarian Cancer Registry reveals evidence for mendelian dominant inheritance.
abstract: BACKGROUND
  Familial component is estimated to account for about 10% of ovarian cancer. However, the mode of inheritance of ovarian cancer remains poorly understood. The goal of this study was to investigate the inheritance model that best fits the observed transmission pattern of ovarian cancer among 7669 members of 1919 pedigrees ascertained through probands from the Gilda Radner Familial Ovarian Cancer Registry at Roswell Park Cancer Institute, Buffalo, New York.
  
  
  RESULTS
  Using the Statistical Analysis for Genetic Epidemiology program, we carried out complex segregation analyses of ovarian cancer affection status by fitting different genetic hypothesis-based regressive multivariate logistic models. We evaluated the likelihood of sporadic, major gene, environmental, general, and six types of Mendelian models. Under each hypothesized model, we also estimated the susceptibility allele frequency, transmission probabilities for the susceptibility allele, baseline susceptibility and estimates of familial association. Comparisons between models were carried out using either maximum likelihood ratio test in the case of hierarchical models, or Akaike information criterion for non-nested models. When assessed against sporadic model without familial association, the model with both parent-offspring and sib-sib residual association could not be rejected. Likewise, the Mendelian dominant model that included familial residual association provided the best-fitting for the inheritance of ovarian cancer. The estimated disease allele frequency in the dominant model was 0.21.
  
  
  CONCLUSIONS
  This report provides support for a genetic role in susceptibility to ovarian cancer with a major autosomal dominant component. This model does not preclude the possibility of polygenic inheritance of combined effects of multiple low penetrance susceptibility alleles segregating dominantly.
authors.affiliation: Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Bamidele O
authors.initials: BO
authors.lastname: Tayo
authors.forename: Richard A
authors.initials: RA
authors.lastname: DiCioccio
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liang
authors.forename: Maurizio
authors.initials: M
authors.lastname: Trevisan
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cooper
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.forename: Lara
authors.initials: L
authors.lastname: Sucheston
authors.forename: Steven M
authors.initials: SM
authors.lastname: Piver
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
mesh_terms: D000483:Alleles; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D008962:Models, Theoretical; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D012042:Registries