GENETIC-FACTORS IN THE PATHOGENESIS OF BREAST-CANCER - THEIR ROLE ANDRELATIVE IMPORTANCE

Aggregation of breast cancer in families is an established risk factor associated with increased incidence of the disease, which is a leadin g 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 express ion: 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 availab le to implicate three additional genes that fit this category: AT, ESR and HRAS1. An area of active interest is genetically mediated variati on in the metabolism of estrogens, a process controlled by several gen es, each with more modest effects. The interaction of genes and enviro nmental factors in breast cancer pathogenesis is of considerable publi c health importance.