UCSF

Despite advancements in antiemetic prophylaxis, chemotherapy-induced nausea (CIN) continues to be a significant clinical problem. Between 30% to 60% of oncology patients experience CIN. While a number of demographic and clinical characteristics are established risk factors CIN, these phenotype risk factors do not explain all of the variance in the occurrence of CIN. The purposes of this dissertation research were to: perform a systematic review of the literature on the associations between single nucleotide polymorphisms (SNPs) in candidate genes and the occurrence of CIN; determine additional risk factors associated with the occurrence of CIN; and determine additional molecular mechanisms associated with the occurrence of CIN.

Sixteen studies evaluated for associations between genomic markers and the occurrence and/or severity of chemotherapy-induced nausea and vomiting (CINV). Candidate genes in the major mechanistic pathways for CINV (i.e., serotonin receptor pathway, drug transport pathway and/or drug metabolism) were evaluated for associations with the occurrence and severity of CINV. In brief, none of the SNPs in these mechanistic pathways were associated with CIN occurrence.

Demographic and clinical risk factors were evaluated for their associations with CIN occurrence. In addition, the impact of concurrent symptoms, stress associated with cancer and its treatment, as well as quality of life (QOL) outcomes on the occurrence of CIN were investigated in patients prior to their next dose of chemotherapy (CTX). Modifiable risk factors identified in this study include: having child-care responsibilities; poorer functional status; and higher levels of depression, sleep disturbance, evening fatigue, perceived stress, and intrusive thoughts and feelings. Patients who reported CIN experienced decrements in QOL outcomes.

Because findings regarding associations between mechanistically-based candidate genes and CIN occurrence were inconclusive, a hypothesis-generating study was undertaken to uncover novel mechanisms associated with CIN occurrence. Findings from this dissertation research suggest that a number of differentially expressed genes and perturbed pathways in the gut-brain axis are associated with the occurrence of CIN. CTX-induced changes in the GBA that may contribute to the occurrence of CIN include: mucosal inflammation and disruption of the gut microbiome. This dissertation concludes with implications for clinical practice and directions for future research.