The interleukin-6 gene: a susceptibility factor that may contribute to racial and ethnic disparities in breast cancer mortality.

Breast cancer prognosis differs among racial and ethnic groups. Though the incidence of breast cancer is lower in African-Americans than in Caucasians, mortality is higher. While socioeconomic, psychosocial, and lifestyle issues are undoubtedly important in such disparities, genetic factors that differ among populations and that are involved in the molecular pathways regulating tumor development may also play roles. In this communication, I summarize recent investigations of the gene encoding the pro-inflammatory cytokine interleukin-6 (IL-6), and suggest that this gene is a susceptibility factor that determines racial and/or ethnic differences in breast cancer survival. Published studies of a G/C polymorphism at nucleotide -174 within the promoter region of the IL-6 gene are consistent with this suggestion. This polymorphism alters expression of the cytokine. In addition, allele and genotype frequencies at the -174 site differ dramatically among racial and ethnic groups. Finally, the variant genotypes are associated with alterations in breast cancer survival. In all, these observations argue for additional studies of the IL-6 gene polymorphism as a predisposing genetic factor that contributes to racial and ethnic differences in breast cancer prognosis.