AN ANALYTICAL METHOD FOR ASSESSING PATTERNS OF FAMILIAL AGGREGATION IN CASE-CONTROL STUDIES

This paper describes an analytical method that is used to assess patterns of disease aggregation within family based on family history information collected in case-control studies. In such a study, cases and controls are thought of as probands whose relatives are identified, and relatives' phenotypes and other covariates such as age, sex, and genealogical relationship with the probands are recorded. By modeling the dependence of relatives' phenotypes on case-control status and other covariates, this method yields adjusted odds ratios that quantify familial aggregation. The estimated standard errors are obtained for statistical inference since the method acknowledges the potential correlations between relatives' phenotypes by using the estimating equations technique. In population-based case-control studies, the estimates and statistical inferences are generalizable to the general population. To illustrate this method, we analyzed a case-control study of colorectal cancer involving 5,190 relatives of 792 cases and 4,478 relatives of 680 population-based controls conducted in Hawaii. Although detailed results will be presented elsewhere, the colorectal cancer was found to aggregate within family with an odds ratio of 2.74 (95% confidence interval (CI): 1.78-4.21). Among parents, the odds ratio for familial aggregation was 2.38 (95% CI: 1.25-4.54). The corresponding value for siblings was 3.09 (95% CI: 1.87-5.11). It was also found that the odds ratio increases from about 2.00 for relatives of the probands who were 50 years or older to 7.66 and 12.84 for relatives of the probands who were between 40 and 50 years and under 40 years, respectively, suggesting that the familial aggregation of colorectal cancer decreases as probands' age increases.