Complex Segregation Analysis of Pedigrees from the Gilda Radner Familial Ovarian Cancer Registry Reveals Evidence for Mendelian Dominant Inheritance

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.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.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

The twenty-first century role of Piver-Rutledge type III radical hysterectomy and FIGO stage IA, IB1, and IB2 cervical cancer in the era of robotic surgery: a personal perspective

Type III radical hysterectomy reported in 1974 by Piver, Rutledge, and Smith is considered worldwide by many as the standard surgical therapy for invasive cervical carcinoma stage IB and IIA. With the increasing number of robotic surgeries being performed for early stage cervical cancer worldwide, the purpose of the paper is to present our personal perspective of the 21st century role of Piver-Rutledge type III radical hysterectomy for stage IB cervical cancer in the era of robotic surgery using the da Vinci robot

Distributions of numbers of nuclear families and inheritance vector bit in the 1919 pedigrees.

<p>Distributions of numbers of nuclear families and inheritance vector bit in the 1919 pedigrees.</p