Analysis of age of onset data from case-control family studies

Age of onset data from case-control family studies are frequently used to study the relationship between disease and environmental or genetic factors. Dependence of age of onset within family and case-control sampling designs must be taken into account in analyzing such data. In this paper, we propose a parametric likelihood approach to study the relationship between disease risk and covariates, allowing for any correlations in age of onset of disease between family members and to study the familial association in age of onset of disease due to genetic factors, after adjusting for other shared covariates within the family. The method provides a way to combine the information relating disease incidence to risk factors in relatives with the information contained in the case/control contrasts in order to obtain more precise estimates of the effects of the putative risk factors. A data set from a case-control family study of lung cancer is used to illustrate the method. The analysis indicated that history of smoking, passive smoking, and history of chronic obstructive pulmonary disease are positively associated with lung cancer risk, and that, after adjustment for these risk factors, there is little evidence of familial aggregation in lung cancer risk.