Identification and prioritization of candidate genes for symptom variability in breast cancer survivors based on disease characteristics at the cellular level

Abstract

Research is beginning to suggest that the presence and/or severity of symptoms reported by breast cancer survivors may be associated with disease-related factors of cancer. In this article, we present a novel approach to the identification and prioritization of biologically plausible candidate genes to investigate relationships between genomic variation and symptom variability in breast cancer survivors. Cognitive dysfunction is utilized as a representative breast cancer survivor symptom to elucidate the conceptualization of and justification for our cellular, disease-based approach to address symptom variability in cancer survivors. Initial candidate gene identification was based on genes evaluated as part of multigene expression profiles for breast cancer, which are commonly used in the clinical setting to characterize the biology of cancer cells for the purpose of describing overall tumor aggressiveness, prognostication, and individualization of therapy. A list of genes evaluated within five multigene expression profiles for breast cancer was compiled. In order to prioritize candidate genes for investigation, genes used in each profile were compared for duplication. Twenty-one genes (BAG1, BCL2, BIRC5, CCNB1, CENPA, CMC2, DIAPH3, ERBB2, ESR1, GRB7, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2) are utilized in two or more profiles, including five genes (CCNB1, CENPA, MELK, MYBL2, and ORC6) used in three profiles. To ensure that the parsimonious 21 gene set is representative of the more global biological hallmarks of cancer, an Ingenuity Pathway Analysis was conducted. Evaluation of genes known to impact pathways involved with cancer development and progression provide a means to evaluate the overlap between the biological underpinnings of cancer and symptom development within the context of cancer.

Keywords:

• breast neoplasms
• biological markers
• genes
• signs and symptoms
• cognition

Acknowledgments

This project was supported by the Targeted Research and Academic Training for Nurses in Genomics (T32NR009759) training program and the Cognitive Function and Breast Cancer: Genomics and Disease Characteristics (F31NR014590) study. The authors acknowledge Dr Susan Cohen, PhD, FNP-BC, FAAN, and members of the University of Pittsburgh Cancer Survivorship Research Seminar for thoughtfully reviewing this manuscript. Portions of this project were presented at the International Society of Nurses in Genetics (ISONG) Silver Anniversary Conference in 2013.

Disclosure

The authors report no conflicts of interest in this work.