High rates of APOBEC-signature mutations are found in many tumors, but factors affecting this mutation pattern are not well understood. Here, we explored the contribution of two common germline variants in the APOBEC3 region. A single nucleotide polymorphism, rs1014971, was associated with bladder cancer risk, increased APOBEC3B expression, and enrichment with APOBEC-signature mutations in bladder tumors. In contrast, a 30 Kb deletion that eliminates APOBEC3B and creates APOBEC3AB chimera, was not important in bladder cancer, while being associated with breast cancer risk and enrichment with APOBEC-signature mutations in breast tumors. In vitro, APOBEC3B was predominantly induced by treatment with a DNA-damaging drug in bladder cancer cell lines and APOBEC3A was induced as part of antiviral interferon-stimulated response in breast cancer cell lines. These findings suggest a tissue-specific role of environmental oncogenic triggers, particularly in individuals with germline APOBEC3 risk variants.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.