The contribution of inherited genotype to breast cancer

Abstract

The etiology of breast cancer is complex, and is likely to involve the actions of genes at multiple levels along the multistage carcinogenesis process. These inherited genotypes include those that affect the propensity to be exposed to breast carcinogens, and those associated with breast tumorigenesis directly. In addition, inherited genotypes may influence response to breast cancer chemoprevention and treatment. Studies relating inherited genotypes with breast cancer incidence and mortality should consider a broader spectrum of genes and their potential roles in multistage carcinogenesis than have been typically evaluated to date. Understanding the role of inherited genotype at different stages of carcinogenesis could improve our understanding of cancer biology, may identify specific exposures or events that correlate with carcinogenesis, or target relevant biochemical pathways for the development of preventive or therapeutic interventions.

Figure 1

Role of inherited susceptibility genotypes along the continuum of multistage carcinogenesis to determine exposure (G_E), disease risk (G_D), efficacy and response to chemoprevention (GP) or treatment (G_T), and natural history or disease outcome (G_O). B denotes biomarkers of exposure (B_exposure), internal dose (B_{internal dose}), effective dose (B_{effective dose}), or early effect (B_{early effect}) as defined by Schulte and Perera [12].