Genetic factors in the etiology of breast cancer

Abstract

Human breast cancer appears to be a heterogeneous disease whose causes are at present unknown. A variety of interrelated genetic, environmental, sociobiologic and physiological factors appear to be associated with increased risk of breast cancer, but no single factor or combination of variables presently known are sufficient to explain the etiology of the disease. Evidence for a genetic role in susceptibility to breast cancer is based on findings from several lines of investigation including: 1) family history of breast cancer, especially bilaterality, 2) marked difference in rates between certain racial groups; 3) lack of major change in incidence of breast cancer over many years despite dramatic changes in other cancers; 4) concordance of breast cancer in monozygotic twins, and 5) concordance of laterality of breast cancer in closely related patients. Recognition of familiality and bilaterality has important clinical value in the identification of high-risk women for special screening and diagnostic studies. It is not known if a single gene or several genetic mutations are responsible for a specific predisposition to breast cancer. Possible genetic traits that control or influence physiological functions of the breast may be inherited by certain women. These genetic factors that increase or decrease the probability of neoplastic transformation may operate through their control over viral, hormonal or other stimuli and through their regulation of the response of the alveolar-ductal epithelium of the breast to these stimuli and to secreted extrinsic carcinogens. A working hypothesis has been developed that interrelates genetic-environmental interactions in breast cancer etiology and pathogenesis. In this model, the turnover rate of breast secretions is the primary determinant of the extent and duration of exposure of the breast epithelium to extrinsic and endogenous carcinogens. The model emphasizes interaction of genetic, physiological, endocrine and environmental factors in the epidemiology of breast cancer.