Limitations of evaluating risks of all cancers combined in etiological epidemiology research

Abstract

The International Agency for Research on Cancer (IARC) was the first public health agency to conclude that an agent – in this case, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) – could be carcinogenic based on associations with all cancers combined, even though there were no consistent associations with any particular cancer type. Most types of cancer each represent an etiologically distinct disease. Epidemiology associations with all cancers combined may be false-positive findings, which lack biological meaning and do not adequately consider confounders, or could mask true associations with specific and/or rare cancer types. We propose that, if investigators report results of etiological analyses with all cancers or groups of etiologically distinct cancers (or other diseases), they consider the heterogenous nature of cancer and that their observations are hypothesis-generating statistical associations without an immediate mechanistic inference.