Mutations in Breast Cancer Exome Sequences Predict Susceptibility to Infections and Converge on the Same Signaling Pathways

Abstract

Many mutations in breast cancer exome sequences alter susceptibility to infections. An exhaustive analysis of all the mutations in exomes from 103 breast cancer cases found that more than 1,000 genes have a published association with some kind of infection, including all known tumor viruses. Altered susceptibility to infection was identified as a common thread connecting breast cancer mutations in genes traditionally classified as coding for diverse functions, including cell immunity, cell architectural barriers, stromal interactions, cell adhesion, DNA damage responses, translation, cell cycle control, metabolism, homeostasis, transport, and neurosensing. Infections and mutations can both contribute to cancer because they deregulate the same pathways. In many cases, infections make a contribution to cancer that is either known or biologically plausible. Interventions may be possible to prevent occult infections from cooperating with mutations to cause further cancer, metastasis, or other complications. The emerging list of infection–gene mutation associations is readily scalable to routine testing of large human data sets.