Cytokine Gene Variations are Associated with Levels of Exercise in Women Prior to Breast Cancer SurgeryBy Nadia Haas Background - Over 90% of women with breast cancer undergo surgery. Although the benefits of exercise prior to and following surgery have been demonstrated, many breast cancer patients exercise below the recommended level. Genetic variation may account for 30-70% of a persons regular level of exercise. Genes associated with exercise include ones involved inflammatory and anti-inflammatory processes. Purpose - The purposes of this study is, in a sample of women evaluated prior to breast cancer surgery were to: evaluate for differences in demographic and clinical characteristics between patients who did (n=78) and those who did not (n=120) exercise on a regular basis and evaluate for associations between exercise group membership and cytokine gene variations. Methods - This study draws its data from a larger longitudinal study on lymphedema and neuropathic pain in women follow breast cancer surgery. Patients completed enrollment questionnaires, and levels of exercise, demographic and clinical characteristics were obtained. Genotype data was obtained DNA isolated from peripheral blood. Three exercise groups were created using guidelines from Healthy People 2020: patients who did not exercise (NoEX, n=120), patients who exercised less than 150 minutes/week (LessEX, n=134), and patients who exercised for the recommended 150 minutes/week (RecEX, n=78). Differences in demographic and clinical characteristics between the NoEX and RecEx groups. Genetic variations of pro-inflammatory, anti-inflammatory and transcriptional regulators were tested for associations with membership in the NoEX and RecEx groups. Results - As compared to the RecEX group, patients in the NoEX group had fewer years of education, were less likely to be White or Asia/Pacific Islander, more like to be Hispanic or of mixed ethnic background, and more likely to report a lower annual household income. Clinically, as compared to the RecEX group, patients in the NoEX group had a higher Body Mass Index (BMI), a lower KPS score, a higher SCQ score, were more likely to self-report a diagnosis of high blood pressure, and were more likely to have received neoadjuvant chemotherapy. In the final multivariate regression models, variations in two SNPs were associated with RecEX or NoEX group membership: IFNGR1 rs9376268 (p-value = 0.021) and NFKB1 rs4648135 (p-value = 0.006). Both loci are in high linkage with missense SNPs located in putative regulatory regions. Conclusions - This study is the first to identify non-modifiable demographic risk factors and modifiable clinical characteristics associated with lack of exercise in patients prior to breast cancer surgery. This exploratory candidate gene study is also the first to identify variations in a cytokine gene and a regulatory gene that are associated with lack of exercise in patients prior to breast cancer surgery. Given the anti-inflammatory effects of exercise can protect against the development of chronic conditions and improve overall health, our findings on the association between exercise and cytokine gene variations may explain some of the beneficial effects of exercise found in studies of patients with and survivors of breast cancer. In addition, given that exercise improves the quality of life of patients with breast cancer, clinicians can use the characteristics identified in this study (e.g. higher BMI, co-morbidities) to identify high risk patients. Furthermore, clinicians should identify barriers to regular exercise and counsel patients on the benefits of regular exercise during and following cancer treatment.