Disease heterogeneity: does it impact our ability to detect dietary associations with breast cancer?

It is generally believed that breast cancer is a multistage process and that multiple and varying genetic events occur on the pathway to disease. We hypothesize that disease heterogeneity has an impact on our ability to identify risk factors. If a genetic alteration occurred in 50% of cases and a risk factor was associated only with that specific alteration, a risk estimate of 1.6 would be detected rather than the true risk estimate of 2.5 if analyses had been limited to those cases with the genetic alteration. Based on the literature we know that many genetic alterations occur in less than 50% of breast tumors. Thus, if environmental factors are related to some, but not all genetic alterations, we are decreasing our ability to identify potentially important risk factors. We therefore hypothesize that identification of dietary factors associated with breast cancer has been hampered by our inability to identify and capture the unique disease pathways which exist and contribute to the heterogeneity of common cancers such as breast cancer.