ANALYSIS OF SWEDISH MALE BREAST-CANCER FAMILY DATA - A SIMPLE WAY TO INCORPORATE A COMMON SIBLING EFFECT

Based on a population-based cohort study, Olsson et al. [1993] found s ignificant evidence for elevated incidence of breast and ovarian cance rs among female first-degree relatives of men with breast cancer. Usin g an extension of logistic regressive models we investigate whether, a fter allowing for multifactorial familial correlations, single locus s egregation could be the cause of the elevated incidence in these famil ies. The legit for a given sib in the class D logistic regressive mode l depends on the order in which affected sibs occur in a sibship. That makes the model less appropriate for the situation where a polygenic component or a common sibling environment may be present, as well as b eing computationally cumbersome. In this paper, we propose to use the proportion of siblings in a sibship who are affected to quantify a sib ling correlation. That not only relaxes the interchangeability problem but also makes the model computationally efficient. We then use this modified class D logistic regressive model for our segregation analysi s. Using the proportion of siblings in a sibship who are affected as a covariate resulted in a significantly higher likelihoods in all the m odels we investigated. We found evidence for a dominant Mendelian gene leading to early age of onset of breast and/or ovarian cancer. This c ould either be a germline mutation of BRCA2 or a mutation in a gene di fferent from BRCA2. (C) 1998 Wiley-Liss, Inc.