EPIDEMIOLOGIC AND GENETIC FOLLOW-UP-STUDY OF 544 MINNESOTA BREAST-CANCER FAMILIES - DESIGN AND METHODS

In 1944, a case-control family study was initiated at the Dight Instit ute for Human Genetics at the University of Minnesota to study the inf luences of childbearing, breastfeeding, and hereditary susceptibility on the occurrence and age-of-onset of breast cancer. Index cases (prob ands) were women ascertained at the Tumor Clinic of the University of Minnesota Hospital. Medical history and life style information were ob tained on probands and relatives, and all cancers were histologically verified. A total of 544 families were studied, with probands diagnose d between 1931 and 1952. All of the records and pathology slides have been maintained from the original study; for most probands this includ es the original tissue blocks. We are conducting a historical cohort s tudy of selected first- and second-degree female relatives (sisters, d aughters, nieces, granddaughters) of the probands and a group of contr ol women identified as the spouses of all male first- and second-degre e relatives (brothers, sons, grandsons, and nephews). The subsequent d evelopment of breast cancer is being determined to quantify the absolu te risk associated with a positive family history. Current disease sta tus is ascertained with mammography, and stromal density is measured u sing digital imaging. Segregation analysis will be applied to examine how non-genetic factors such as diet, exogenous hormone use, and body fat distribution influence risk in women at high risk because of famil y history. A subset of families are being selected for molecular analy sis of the BRCA1 gene or for linkage analyses to identify putative sus ceptibility loci other than BRCA1. Documented cancer histories were kn own for at least three generations, and the current study extends the pedigrees up to four or five generations for every family, allowing a detailed description of familial risk. This cohort study of breast can cer families is likely to be important in both quantity and quality of data and will serve as a major genetic epidemiologic resource, being free of selection bias and having relevant non-genetic exposure determ ined in at least four generations. (C) 1995 Wiley-Liss, Inc.