Genetic factors in the pathogenesis of breast cancer: their role and relative importance.

Aggregation of breast cancer in families is an established risk factor associated with increased incidence of the disease, which is a leading cause of morbidity and mortality among women in this country. Three genes have now been identified that confer increased susceptibility in families with a clear hereditary (i.e., Mendelian) pattern of expression: BRCA1, BRCA2 and p53. However, a significant number of women have an identified family history of breast cancer without clear Mendelian patterns of disease. Such patterns are consistent with the effect of more common genes with lower associated risk. Some evidence is available to implicate three additional genes that fit this category: AT, ESR and HRAS1. An area of active interest is genetically mediated variation in the metabolism of estrogens, a process controlled by several genes, each with more modest effects. The interaction of genes and environmental factors in breast cancer pathogenesis is of considerable public health importance.