Examination of heterogeneity in 200 Danish breast cancer pedigrees.

Abstract

The clinical impression of the expression of breast cancer includes the notion of etiological heterogeneity. The incidence of breast cancer rises in postmenopausal women and is very rare among males. The roles of putative genetic susceptibility factors, changing estrogen levels, and possible environmental agents are not clearly defined as they relate to the differential incidences. Williams and Anderson (1984) proposed that a dominant major gene influences the risk for breast cancer in the set of Danish pedigrees ascertained by Jacobsen and analyzed in the present investigation. Williams and Anderson evaluated the internal consistency of their conclusions by evaluating heterogeneity within pedigrees that were partitioned into sibships based on relation to the proband; they found no evidence of heterogeneity. In contrast, Elston and Bailey-Wilson (this volume) carried out a test of consistency of a dominant major gene model with the entire Jacobsen data set and found support for the notion of heterogeneity. An alternative to the search for heterogeneity within lineages, as done by Williams and Anderson, is to seek heterogeneity between families, based on clinically relevant data.