Investigating the relationship between melatonin patterns and methylation in circadian genes among day shift and night shift workers.

OBJECTIVES: Mechanisms underlying the carcinogenicity of night shift work remain uncertain. One compelling yet understudied cancer mechanism may involve altered DNA methylation in circadian genes due to melatonin secretion patterns. The objective of this study was to explore the relationship between melatonin secretion patterns and circadian gene methylation among day and night shift workers. METHODS: Female healthcare employees (n=38 day workers, n=36 night shift workers) for whom we had urinary 6-sulfatoxymelatonin secretion data from a previous study were recontacted. New blood samples were collected and used to measure methylation levels at 1150 CpG loci across 22 circadian genes using the Illumina Infinium MethylationEPIC beadchip. Linear regression was used to examine the association between melatonin (acrophase and mesor) and M values for each CpG site (false discovery rate, q=0.2), while testing for effect modification by shift work status. RESULTS: Among night shift workers, a higher mesor (24 hours of mean production of melatonin) was associated with increased methylation in the body of RORA (q=0.02) and decreased methylation in the putative promoter region of MTNR1A (q=0.03). Later acrophase (ie, time of peak concentration) was associated with increased methylation in the putative promoter region of MTNR1A (q=0.20) and decreased methylation in the body of PER3 (q=0.20). No associations were identified among day workers. CONCLUSIONS: In conclusion, patterns in melatonin secretion were associated with differential circadian gene methylation among night shift workers. Melatonin and alteration of DNA methylation in circadian genes may be one pathway towards increased cancer risk, although larger-scale studies examining multiple time points are needed.

Exploring the impact of night shift work on methylation of circadian genes.

Night shift work is associated with increased breast cancer risk, but the molecular mechanisms are not well-understood. The objective of this study was to explore the relationship between night shift work parameters (current status, duration/years, and intensity) and methylation in circadian genes as a potential mechanism underlying the carcinogenic effects of night shift work. A cross-sectional study was conducted among 74 female healthcare employees (n = 38 day workers, n = 36 night shift workers). The Illumina Infinium MethylationEPIC beadchip was applied to DNA extracted from blood samples to measure methylation using a candidate gene approach at 1150 CpG loci across 22 circadian genes. Linear regression models were used to examine the association between night shift work parameters and continuous methylation measurements (ß-values) for each CpG site. The false-discovery rate (q = 0.2) was used to account for multiple comparisons. Compared to day workers, current night shift workers demonstrated hypermethylation in the 5'UTR region of CSNK1E (q = 0.15). Individuals that worked night shifts for ≥10 years exhibited hypomethylation in the gene body of NR1D1 (q = 0.08) compared to those that worked <10 years. Hypermethylation in the gene body of ARNTL was also apparent in those who worked ≥3 consecutive night shifts a week (q = 0.18). These findings suggest that night shift work is associated with differential methylation in core circadian genes, including CSNK1E, NR1D1 and ARNTL. Future, larger-scale studies with long-term follow-up and detailed night shift work assessment are needed to confirm and expand on these findings.

A cross-sectional study of breast cancer biomarkers among shift working nurses.

Objectives In 2007, the International Agency for Research on Cancer classified long-term shift work as a probable carcinogen, with the strongest evidence for breast cancer. One proposed mechanism involves night-time light exposure and decreases in melatonin, a circadian rhythmic hormone. It is hypothesised that melatonin influences patterns of sex hormone production that in turn influence breast cancer risk. This study sought to investigate the relationships of shift work history, 6-sulfatoxymelatonin (aMTs-6, the primary melatonin metabolite) and sex hormone levels among shift working nurses. Design This is a cross-sectional biomarker study. Setting 94 premenopausal nurses who work a full-time rotating shift schedule at one Ontario hospital were recruited for this study; 82 completed follow-up. Primary and secondary outcome measures Study participants provided morning void urine and fasting blood samples for the assessment of aMTs-6 and sex hormone (oestradiol, oestrone, progesterone, prolactin) levels, respectively. These data were collected at two time points (summer and winter) such that relationships between melatonin and sex hormones could be assessed with respect to two time frames of interest (acute and cross-seasonal). Results An inverse relationship between aMTs-6 and oestradiol was suggested in the winter (ß=-0.18, p=0.04), but this result was not statistically significant in multivariate modelling that adjusted for age, body mass index and menstrual cycle. Likewise, while oestradiol, oestrone and progesterone levels increased with greater years of shift work history (all p<0.05), these associations were attenuated after confounder adjustment. Conclusions These results do not support the proposed relationship between melatonin and sex hormone levels as biomarkers on the pathway of shift work and breast cancer but emphasise the importance of adjusting for confounders in modelling.

Fatigue and physical activity in older adults with cancer: a systematic review of the literature.

Cancer is a disease predominantly affecting older adults. Cancer fatigue is the most common and often most distressing symptom associated with cancer and its treatment, often persisting months to years after treatment. Untreated cancer fatigue may lead to significant reductions in physical activity, physical functioning, and quality of life and may interfere with patients' adherence to cancer treatment. Physical activity has the strongest supporting evidence as an intervention to reduce cancer fatigue, maintain physical function, and optimize quality of life. This article reviews the literature related to fatigue and physical activity in older adults with cancer. Nine experimental and 10 observational studies that enrolled subjects 65 years or older were synthesized in the review and provided evidence that physical activity may be an effective intervention for cancer fatigue in older adults. The generalizability of the findings to older adults was limited by the poor representation of this age group in the studies. Few studies provided an analysis of age-related effects of physical activity on fatigue, physical function, and quality of life.

Understanding the supportive care needs of parents of children with cancer: an approach to local needs assessment.

The objective of this study was to conduct an assessment of supportive care needs from the perspective of parents of children diagnosed with cancer within an urban-rural region in Eastern Ontario, Canada. Guided by a conceptual framework for supportive care, the exploratory, mixed-method study used a standard needs survey and semistructured interviews. Fifteen parents completed (75% response rate) the survey, and 3 parents participated as key informants in the follow-up interview. Parents reported needs in all 6 of the need categories outlined within the Supportive Care Needs Framework. The proportion of parents expressing a need ranged from 23% to 39%. Dealing with the fear of their child's cancer spreading was frequently identified by parents. Emotional and informational needs were the 2 most frequently acknowledged categories of need. With further refinement, the use of the conceptual framework will provide a methodology for planning care based on the individual needs identified by parents of children with cancer.

Enhancing postoperative recovery of cardiac surgery patients: a randomized clinical trial of an advanced practice nursing intervention.

The purpose of this trial was to determine the effectiveness of advanced practice nursing support on cardiac surgery patients' during the first 5 weeks following hospital discharge. Patients ( N = 200) were randomly allocated to two groups: (a) an intervention group who received telephone calls from an advanced practice nurse (APN) familiar with their clinical condition and care needs, twice during the first week following discharge then weekly thereafter for 4 weeks, and (b) a usual care group. Measures of health-related quality of life (HRQL), symptom distress, satisfaction with recovery care, and unexpected health care contacts were obtained at 5 weeks following discharge. There were no significant group differences in HRQL, unexpected contacts with the health care system, or symptom distress. The provision of APN support via telephone followup after cardiac surgery is feasible. However, further randomized trials of single and multicomponent APN interventions are needed to prove effectiveness.

Measuring the symptom experience of seriously ill cancer and noncancer hospitalized patients near the end of life with the memorial symptom assessment scale.

The objectives of this study were twofold: (1) to explore and compare the symptom experience of seriously ill hospitalized cancer and noncancer patients near the end of life using the Memorial Symptom Assessment Scale (MSAS) and (2) to determine if the MSAS is a valid and useful measure of symptom distress for patients with noncancer conditions. This was a prospective cohort study of hospitalized patients with end-stage congestive heart disease, chronic pulmonary disease, cirrhosis, or metastatic cancer. Eligible patients were interviewed to ascertain symptom prevalence, severity and distress using the MSAS and levels of fatigue using the Piper Fatigue Scale (PFS). Sixty-six patients with metastatic cancer and 69 patients with end-stage disease were enrolled in the study. There was a significant difference in the prevalence of selected physical symptoms, but not psychological symptoms, between cancer and noncancer patients. There were no significant differences in symptom distress scores, a computed score of frequency, severity and distress, if the symptom was present. In both groups the principal components factor analysis with varimax rotation yielded one factor comprising psychological symptoms and a second factor comprising three subgroups of physical symptoms. Internal consistency was high for the psychological subscale (Cronbach alpha coefficients of 0.85 for the cancer group and 0.77 for the noncancer group) and for the physical subscale groupings, with coefficients ranging between 0.78 to 0.87. The symptom scores were significantly correlated with perceptions of fatigue. These findings show that both seriously ill cancer and noncancer patients experience symptom distress, and that the MSAS seems to be a reliable measure of symptom distress in noncancer patients, as well as with cancer patients.