Physical activity and telomere length in early stage breast cancer survivors.

INTRODUCTION: Telomere length (TL) is a biomarker of accumulated cellular damage and human aging. Evidence in healthy populations suggests that TL is impacted by a host of psychosocial and lifestyle factors, including physical activity. This is the first study to evaluate the relationship between self-reported physical activity and telomere length in early stage breast cancer survivors. METHODS: A cross-sectional sample of 392 postmenopausal women with stage I-III breast cancer at an outpatient oncology clinic of a large university hospital completed questionnaires and provided a blood sample. TL was determined using terminal restriction fragment length analysis of genomic DNA isolated from peripheral blood mononuclear cells. Physical activity was dichotomized into two groups (none versus moderate to vigorous) using the International Physical Activity Questionnaire. Multivariate linear and logistic regression analyses were performed to identify factors associated with mean TL and physical activity. RESULTS: Among participants, 66 (17%) did not participate in any physical activity. In multivariate model adjusted for age, compared to those who participated in moderate to vigorous physical activity, women who participated in no physical activity had significantly shorter TL (adjusted coefficient ß=-0.22; 95% confidence interval (CI), -0.41 to -0.03; P=.03). Non-white race, lower education and depressive symptoms were associated with lack of self-reported physical activity (P<0.05 for all) but not TL. CONCLUSION: Lack of physical activity is associated with shortened TL, warranting prospective investigation of the potential role of physical activity on cellular aging in breast cancer survivors.

Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors.

INTRODUCTION: Aromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synthesis, may be associated with the occurrence of AIAA. METHODS: We performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving adjuvant aromatase inhibitor (AI) therapy. Patient-reported AIAA was the primary outcome. DNA was genotyped for candidate CYP19A1 polymorphisms. Serum estrogen levels were evaluated by radioimmunoassay. Multivariate analyses were performed to examine associations between AIAA and genetic variants controlling for possible confounders. RESULTS: Among 390 Caucasian participants, 50.8% reported AIAA. Women carrying at least one 8-repeat allele had lower odds of AIAA (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.21 to 0.79, P = 0.008) after adjusting for demographic and clinical covariates. Estradiol and estrone were detectable in 47% and 86% of subjects on AIs, respectively. Although these post-AI levels were associated with multiple genotypes, they were not associated with AIAA. In multivariate analyses, women with more recent transition into menopause (less than five years) were significantly more likely to report AIAA than those greater than ten years post-menopause (AOR 3.31, 95% CI 1.72 to 6.39, P < 0.001). CONCLUSIONS: Functional polymorphism in CYP19A1 and time since menopause are associated with patient-reported AIAA, supporting the hypothesis that the host hormonal environment contributes to the pathophysiology of AAIA. Prospective investigation is needed to further delineate relationships between host genetics, changing estrogen levels and AIAA.

A nested case-controlled comparison of telomere length and psychological functioning in breast cancer survivors with and without insomnia symptoms.

The ability to achieve sufficient restorative sleep is important in the maintenance of physical and mental health; however, disturbed sleep and insomnia symptoms are a common experience among women with breast cancer. In non-cancer populations, insufficient sleep quantity and quality has been associated with shortened telomere length (TL), a measure of accumulated cellular damage and human aging. This feasibility study compared TL in women previously diagnosed with breast cancer with clinically significant insomnia symptoms (n=70) to an age- and body mass index (BMI)-matched comparison group (n=70) of breast cancer survivors. Women with significant insomnia symptoms had higher levels of unemployment compared to women without insomnia. TL was positively skewed and shorter in the insomnia group (Median=6.000, S=1.000, standard error [SE]=0.287) than the control group (Median=6.195, S=-0.269, SE=0.287); however, this was not significant (p=0.29). Women with insomnia also reported significantly higher levels of depression (p<0.001), anxiety (p<0.001), and fatigue (p<0.001). This study provides the first measure of effect size and variability of TL in women with breast cancer and highlights the need for larger sample sizes to investigate the impact of insomnia and co-morbid symptom distress on cellular aging.