Design and analysis issues in a population-based, case-control-family study of the genetic epidemiology of breast cancer and the Co-operative Family Registry for Breast Cancer Studies (CFRBCS). J Natl Cancer Inst Monogr

ogy ” of cancer have used nonsystematically sampled kin-dreds with numerous cases of cancer across multiple genera-tions. From the epidemiologic viewpoint, it is difficult to extrapolate findings to the population because of the ad hoc ascertainment of these atypical, ill-defined families. Since 1992, we have been conducting a population-based, case– control–family study of breast cancer. Methods: Families are identified through a single, population-sampled proband, who is either affected or unaffected, making adjustment for ascertainment straightforward. Administered question-naires and blood samples are sought from cases, controls, and specified sets of relatives. From 1996 through 1999, a further 1200 case families have been recruited as part of the Co-operative Family Registry for Breast Cancer Studies (CFRBCS). Issues relevant to the study design and analysi