Graduation Year

2018

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Nursing

Major Professor

Cecile A. Lengacher, Ph.D.

Committee Member

Jong Y. Park, Ph.D.

Committee Member

Kevin E. Kip, Ph.D.

Committee Member

Carmen S. Rodriguez, Ph.D.

Keywords

breast cancer, fatigue, genetics, MBSR, pain

Abstract

Breast cancer survivors (BCS) account for the largest group of cancer survivors living in the United States and they often experience lingering physical symptoms that may affect quality of life, with fatigue and pain the most commonly reported. This genetic research study was conducted within a parent R01 study, with the purpose of exploring associations between genetic variants and fatigue and pain symptoms and the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR(BC)) program. The aims of this study were to: 1) identify specific genotypes involved in fatigue and pain symptoms, and 2) explore whether single nucleotide polymorphism (SNP) rs1800795 in gene IL6, SNP rs16944 in gene IL1B, and SNP rs4680 in gene COMT, moderate the effects of the MBSR(BC) intervention on fatigue and/or pain symptoms.

As part of a larger R01 trial, one-hundred-fifty-eight participants were randomized to either a six-week MBSR(BC) intervention or Usual Care (UC). Data were collected at baseline, six-week, and 12-weeks on subjective measures of pain, fatigue, along with demographic and clinical history information. In addition, DNA was collected for genotyping among the 158 participants using the PCR analysis method. For Aim 1, one-way linear trend analysis of variances (ANOVAs) were implemented to explore associations between the SNPs in genes with subjective symptom measures of pain and fatigue. For Aim 2, comparison of mean scores along with linear mixed model (LMM) analyses were used to explore if the patient’s SNPs moderated the effects of the MBSR(BC) intervention on fatigue and pain symptoms.

Results found the mean age of the total sample was 58.4 years and 89% were White, non-Hispanic. Although participants were randomized 1:1 to either the MBSR(BC) or UC groups, chi square analyses found that there was a significant difference for time since treatment, with the UC group being closer to treatment end (< 1 year) than the MBSR(BC) group (p < .05). No other statistically significant differences between groups for baseline demographic or clinical characteristics were found. For Aim 1, one-way linear trend ANOVAs among fatigue and pain scores and the three SNPs (COMT rs4680, IL1B rs16944, IL6 1800795) included as part of this study, fatigue and/or pain, resulted in no statistically significant associations (p > .05). Linear Mixed Model (LMM) analyses, implemented to assess the between-group interactions between pain and/or fatigue symptom, time, and SNP, resulted in no statistically significant findings for SNP rs4680 in COMT and SNP rs16944 in IL1B, however significant findings were found for the interaction between assignment (MBSR(BC) versus UC) and genotype for SNP rs1800795 in IL6. Second, a comparison of means suggests that participants in the MBSR(BC) group who had CG genotype for SNP rs1800795 in IL6 benefited more from the intervention than those with CC or GG genotypes for fatigue severity, fatigue interference, pain severity, and pain interference, with small to large effect sizes ranging from d = 0.38 to d = 0.72. Although this genetic study was exploratory in nature, the results suggests that the effects of the MBSR(BC) program may be moderated by SNPs in genes that are involved in cytokine production, which means that BCS with specific genotypes experience a greater improvement in symptoms than those with other genotypes. The results of this study also suggest that further research is needed, with larger sample sizes, to assess the genetic moderation of symptoms experienced by BCS.

Download

Included in

Nursing Commons

Share

COinS