EVALUATION OF POTENTIAL SOURCES OF BIAS IN A GENETIC EPIDEMIOLOGIC-STUDY OF BREAST-CANCER

Systematic errors, or bias? can arise at several stages of a study, in cluding selection of subjects, measurement of exposure and disease, an d data analysis. Little attention appears to have been paid to potenti al sources of bias in genetic epidemiologic studies, despite the fact that the study of units (families) and members (relatives) within thos e units produces unique opportunities for bias to be introduced. The a bility to evaluate whether selection bias has occurred is rare. In 194 4, a case-control family study of breast cancer was initiated at the D ight Institute for Human Genetics at the University of Minnesota. A fo llow-up study of these 544 families is currently being conducted on si sters, daughters, nieces, and granddaughters of the probands, and a co ntrol group of women who are spouses of male first- and second-degree relatives. Updated data are collected on females who are 18 years or o lder through telephone interviews and questionnaires. The availability of detailed family history information on these families at baseline provided an opportunity to evaluate several potential sources of bias. Analyses were performed to determine if families lost to follow-up di ffered from those who were successfully located or excluded (ineligibl e), and whether participation rates within a family differed by relati onship to proband, age, and family history of cancer. The latter parti cipation rates for individuals were examined with respect to a telepho ne interview, a mailed questionnaire, and screening mammography. There were no statistically significant differences in the cancer histories of families that were excluded, those that were lost to follow-up, an d those that participated. Within families, degree of relationship to the breast cancer proband was significantly associated with age-adjust ed participation rates on mailed questionnaires (P < 0.005) and mammog raphy (P < 0.005), but not telephone interviews (P = 0.29). After adju stment for age, marry-ins with a family history of breast cancer were not significantly more likely than many-ins without a family history t o undergo mammography (P = 0.11) or return mailed questionnaires (P = 0.74). Although non-participation is a potentially serious source of b ias to a genetic epidemiologic study and the effect of variable partic ipation rates should be explored when investigating the genetic compon ent of a disease, it does not appear to be a problem for this particul ar study. (C) 1997 Wiley-Liss, Inc.