ISPO

Published in Cancer Detection and Prevention 1994; 18(3):171-178.

A Method for Estimating Cancer Risk in p53 Mutation Carriers

Christine Le Bihan, Catherine Bonaiti-Pellie, MD, PhD Unite de Recherches d'Epidemiologie Genetique U 155 INSERM, Paris, France

Address all correspondence and reprint requests to: C. Bonaiti- Pellie, U. 155 INSERM, Chateau de Longchamp, Bois de Boulogne, 75016 Paris, France

Address all correspondence and reprint requests to: C. Bonaiti- Pellie, U. 155 INSERM, Chateau de Longchamp, Bois de Boulogne, 75016 Paris, France

ABSTRACT: Germline mutations of the tumor-suppressor gene p53 have been described in families with multiple neoplasms as Li- Fraumeni syndrome families, or in subjects with second malignant tumor. In order to evaluate the increase in risk of cancer due to these mutations, a family study is being carried out. In families with a proband who developed a cancer before age 16, we select those with at least one cancer before age 45 among first- and second-degree relatives of the proband. All family members are screened for p53 germ-line mutations if the proband is a carrier of a mutation. We present here a method to estimate the probability that a carrier of a p53 germline mutation develops a given malignant tumor at a given age. This method uses the principle of maximum likelihood estimation. It takes into account the fact that individuals are related within a family, that some of them are not genotyped for p53, and that families have been selected on the criterion of existence of cancer. Simulated data allowed us to validate the method.

KEY WORDS: p53, risk of cancer, maximum likelihood.

http://www.cancerprev.org/Journal/Issues/18/3/19