Variations in COMT and NTRK2 Influence Symptom Burden in Women Undergoing Breast Cancer Treatment

Abstract

Women with breast cancer frequently report distressing symptoms during and after treatment that can significantly erode quality of life (QOL). Symptom burden among women with breast cancer is of complex etiology and is likely influenced by disease, treatment, and environmental factors as well as individual genetic differences. The purpose of the present study was to examine the relationships between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1 (NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-methyltransferase (COMT) and patient symptom burden of QOL, pain, fatigue, anxiety, depression, and sleep disturbance before, during, and after treatment for breast cancer in a subset of participants (N = 51) in a randomized clinical trial of a novel symptom-management modality for women with breast cancer undergoing chemotherapy. Patients were recruited at the time of initial breast cancer diagnosis and completed all survey measures at the time of recruitment, after the initiation of treatment (surgery and/or chemotherapy), and then following treatment conclusion. Multiple linear regression analyses revealed significant associations between NTRK2 and COMT single nucleotide polymorphism (SNP) genotype and symptom burden. Two COMT variants were associated with the specific symptoms of anxiety and QOL measures prior to the initiation of chemotherapy as well as pain interference and severity during and after treatment. Genotype at the NTRK2 SNP rs1212171 was associated with both sleep disturbance and fatigue. These findings, while exploratory, indicate that the genotypes of NTRK2 and COMT may contribute to relative risk for symptom burden during and shortly after the period of chemotherapy in women with early stage breast cancer.

Precision health: Advancing symptom and self-management science

“…Nurse scientists focus on understanding the biological underpinnings of symptoms that are inherently self-reported subjective phenomena and the extent to which they reflect or predict biological risk or vulnerability to changes in health. Several nurse scientists are conducting research that integrates precision health to better understand symptom burden, to predict or prevent disease, and to optimize individual treatment and quality of life improvement (Cashion, Gill, Hawes, Henderson, & Saligan, 2016; Cashion & Grady, 2015; Lyon et al, 2016; Tantoy et al, 2017; Young et al, 2017). For example, an intramural program of research at NINR is examining the underpinnings of symptom distress mechanisms in digestive disorders, specifically the biobehavioral relationships between inflammation and symptoms (Henderson, 2013).…”

Identification of Key Genes and Pathways in Breast Cancer Based on Bioinformatic Analysis

“…However, in the present study, those observations were not statistically significant. Another bioinformatic analysis found MELK were related to worse OS in BC (Young et al, 2017). CLU might be a predictive factor for recurrence in <T2 stage BC (Yom et al, 2009).…”

The construction and analysis of ceRNA networks in invasive breast cancer: a study based on The Cancer Genome Atlas

“…NTRK2 , a direct target of miR-200c, codes for proteins expressed in mesenchymal or neuron-derived cells and may contribute to the relative risk for symptom burden during and shortly after the period of chemotherapy in women with early-stage breast cancer 41–43. Li et al,44 using the gene microarray analysis, found that miR-105/93-3p activates Wnt/β-catenin signaling by the downregulation of SFRP1 , thereby promoting stem cells, chemoresistance, and TNBC cell metastasis.…”