Genes Relevant to Tissue Response to Cancer Therapy Display Diurnal Variation in mRNA Expression in Human Oral Mucosa.

BACKGROUND: To address a critical gap for application of cancer chronotherapy of when would be the best time(s) for treating an individual cancer patient, we conducted a pilot study to characterize diurnal variations of gene expression in oral mucosal tissue, which is vulnerable to damage from cancer therapies. METHODS: We conducted RNA-seq assay on individual oral mucosal samples collected from 11 healthy volunteers every 4 hours (6 time points). Using a cosine-based method, we estimated the individual and average values of peak-time and amplitude for each gene. Correlations between gene expression peak-times and age was examined, adjusting for individual's sleep timing. RESULTS: Among candidate gene pathways that are relevant to treatment response, 7 of 16 genes (PER3, CIART, TEF, PER1, PER2, CRY2, ARNTL) involved in circadian regulation and 1 of 118 genes (WEE1) involved in cell cycle regulation achieved p-value ≤ 0.1 and relative amplitude>0.1. The average peak times were approximately 10:15 for PER3, CIART and TEF, 10:45 for PER1, 13:00 for WEE1, PER2 and CRY2, and 19:30 for ARNTL. Ranges in peak times across individuals differed by gene (e.g., 8 hours for PER1; 16.7 hours for WEE1). Older people had later peak times for PER1 (r = 0.77, p = 0.03) and PER3 (r = 0.69, p-value = 0.06). CONCLUSION: In oral mucosa, expression of some genes relevant to treatment response displayed diurnal variation. These genes may be candidates for development of biomarkers for optimizing individual timing of cancer therapy using non-invasively collected oral mucosa.

Habitual recreational physical activity is associated with significantly improved survival in cancer patients: evidence from the Roswell Park Data Bank and BioRepository.

PURPOSE: The association of recreational physical activity (RPA) with mortality is well established only for breast and colon cancers and few studies have evaluated relationships for exercising before and after diagnosis, across multiple disease sites. We examined the joint associations of pre- and post- diagnosis RPA with mortality in a cohort of 5,807 patients enrolled in the Data Bank and BioRepository at Roswell Park. METHODS: Patients were classified into one of four activity categories (habitually active, increased activity after diagnosis, decreased activity after diagnosis, habitually inactive). Cox proportional hazards models were used to estimate the associations of activity status with mortality. RESULTS: In comparison to patients who were habitually inactive, habitually active patients experienced a 39% decreased hazard of all-cause mortality (HR = 0.61, 95% CI 0.54-0.69) and a 36% decreased hazard of cancer-specific mortality (HR = 0.64, 95% CI 0.56-0.73). Previously inactive patients who began exercising after diagnosis experienced a 28% decreased hazard of all-cause (HR = 0.72, 95% CI 0.59-0.89) and cancer-specific mortality (HR = 0.72, 95% CI 0.57-0.91) in comparison to patients who remained inactive. Patients engaging in 3-4 sessions/week experienced the greatest survival advantages, but 1-2 sessions/week also yielded significant survival advantages in comparison to inactivity. CONCLUSION: Low-to-moderate frequency pre- and post-diagnosis RPA was associated with significantly decreased mortality in patients diagnosed with a variety of malignancies. These observations solidify the clinical and public health importance of the message that some regular activity is better than inactivity, which is particularly encouraging, given that cancer survivors can be overwhelmed by current daily physical activity recommendations.

Associations between Serum 25-Hydroxyvitamin D Levels and Health-Related Quality-of-Life Measures in Patients with Breast Cancer: A Longitudinal Study.

BACKGROUND: Recent evidence suggests that vitamin D might lower breast cancer mortality. There is also growing interest in vitamin D's potential association with health-related quality-of-life (HRQoL). Associations between circulating 25-hydroxyvitamin D (25OHD) concentrations and HRQoL were examined prospectively among breast cancer survivors at the time of diagnosis and 1 year later. METHODS: 504 women with incident early-stage breast cancer at Roswell Park Comprehensive Cancer Center were included, and 372 patients provided assessments 1 year later. At each timepoint, participants provided blood samples and completed the SF-36 Health Survey, and surveys on perceived stress, depression, and fatigue. Season-adjusted serum 25OHD concentrations were analyzed in relation to HRQoL measures using multivariable logistic regression models. RESULTS: Approximately 32% of participants had deficient vitamin D levels at diagnosis, which decreased to 25% at 1 year. Concurrently, although SF-36 physical health summary scores were lower at 1 year, mental health summary scores improved, and levels of depression and perceived stress were lower. In comparison with women with sufficient 25OHD levels (>30 ng/mL) at diagnosis, those who were deficient (<20 ng/mL) had significantly worse HRQoL at diagnosis and 1 year later. Vitamin D deficiency 1 year post-diagnosis was also associated with worse HRQoL, particularly among breast cancer survivors who took vitamin D supplements. CONCLUSIONS: Breast cancer survivors with vitamin D deficiency were more likely to report lower HRQoL than those with sufficient levels at the time of diagnosis and 1 year post-diagnosis. IMPACT: Our results indicate a potential benefit of vitamin D supplementation for improving breast cancer survivorship.

Parenting Stress during Late Adolescence in Mothers of Individuals with ADHD with and without ODD.

Although children with ADHD continue to experience impairment well into adolescence, research exploring the experiences of their parents during late adolescence is lacking. Thus, we examined changes in parenting stress and family conflict in mothers of adolescents with ADHD during the transition to early adulthood. We also explored predictors of these changes in addition to investigating differences in these trajectories due to comorbid ODD. Forty-nine mothers of adolescents with ADHD only and thirty-seven mothers of adolescents with ADHD/ODD reported on parenting stress and perceptions of family conflict at baseline (mean age = 16.88) and at 3-month, 9-month, and 15-month follow up assessments. Growth curve modeling indicated that both groups of mothers reported relative declines in parenting stress and family conflict across time. However, the mothers of adolescents with ADHD/ODD persistently reported more stress and conflict. Furthermore, decreases in family conflict were more predictive of reduced parenting stress in families of adolescents only diagnosed with ADHD. Our findings suggest that comorbid ODD is associated with parenting stress during late adolescence. Thus, interventions should focus on further reducing this stress as adolescents with ADHD/ODD transition to adulthood.

A school-based parenting program for children with attention-deficit/hyperactivity disorder: Impact on paternal caregivers.

Engaging male caregivers within school settings is a major need within the educational field. Paternal engagement may be particularly important for children with attention-deficit/hyperactivity disorder (ADHD). Children with ADHD have increased risk for a number of poor educational outcomes, which may be attenuated by the benefits of positive male caregiver involvement. The Coaching Our Acting Out Children: Heightening Essential Skills (COACHES) program has been illustrated to be an effective approach for engaging, retaining, and improving the parenting of male caregivers of children with ADHD in clinical settings. The present study reports on the efficacy of the COACHES in Schools program, an adaptation intended for deployment in elementary school settings. Sixty-one male caregivers were randomly assigned to COACHES in Schools or a waitlist control. Results indicated that male caregivers in COACHES in Schools used significantly more praise and less negative talk in a parent-child activity relative to male caregivers in the waitlist control at post-treatment and one-month follow-up. Distal outcomes related to child behavior at home and at school were not significantly different. Implications of the results for future studies and continued efforts to engage male caregivers within school settings are discussed.

Interpersonal Problems of Young Adults With and Without Attention-Deficit/Hyperactivity Disorder.

Objective:Interpersonal functioning is a core area of impairment for young adults with Attention-Deficit/Hyperactivity Disorder (ADHD), yet the assessment of their interpersonal problems has not been approached using a comprehensive model of interpersonal behaviors. Method: Interpersonal problems of young adults with ADHD (n = 24) were compared to non-ADHD peers (n = 26) by self- and collateral-report using the Inventory of Interpersonal Problems-Circumplex-Item Response Theory (IIP-C-IRT). Results: Both self- and collateral-reports yielded significantly higher scores across interpersonal problem domains, except for self-reported Hostile-Dominant (HD) interpersonal problems. Discrepancy scores between self- and collateral-report supported larger differences in the ADHD versus non-ADHD groups for HD problems. Large correlations between collateral-reported family relationship impairments and HD problems were found only for the ADHD group. Conclusion: Young adults with ADHD have higher levels of interpersonal problems relative to their non-ADHD peers, but also appear to underreport HD interpersonal problems relative to non-ADHD peers, suggesting the presence of a bias. (J. of Att. Dis. XXXX; XX[X] XX-XX).

Clinical and Lifestyle-Related Prognostic Indicators among Esophageal Adenocarcinoma Patients Receiving Treatment at a Comprehensive Cancer Center.

PURPOSE: The incidence of esophageal adenocarcinoma (EAC) has risen substantially in recent decades, while the average 5-year survival remains only ~20%. Disease stage and treatment are the strongest prognostic factors. The role of lifestyle factors in relation to survival remains uncertain, with a handful of studies to date investigating associations with obesity, smoking, physical activity, diet, or medications. METHODS: This study included patients diagnosed with primary adenocarcinoma of the esophagus, gastroesophageal junction, or cardia (N = 371) at Roswell Park Comprehensive Cancer Center between 2003 and 2019. Leveraging extensive data abstracted from electronic medical records, epidemiologic questionnaires, and a tumor registry, we analyzed clinical, behavioral, and environmental exposures and evaluated stage-specific associations with survival. Survival distributions were visualized using Kaplan-Meier curves. Cox proportional hazards regression models adjusted for age, sex, stage, treatment, and comorbidities were used to estimate the association between each exposure and all-cause or cancer-specific mortality. RESULTS: Among patients presenting with localized/regional tumors (stages I-III), current smoking was associated with increased overall mortality risk (HR = 2.5 [1.42-4.53], p = 0.002), while current physical activity was linked to reduced risk (HR = 0.58 [0.35-0.96], p = 0.035). Among patients with stage IV disease, individuals reporting pre-diagnostic use of statins (HR = 0.62 [0.42-0.92], p = 0.018) or NSAIDs (HR = 0.61 [0.42-0.91], p = 0.016) had improved overall survival. Exploratory analyses suggested that high pre-diagnostic dietary consumption of broccoli, carrots, and fiber correlated with prolonged overall survival in patients with localized/regional disease. CONCLUSION: Our data suggest that lifestyle exposures may be differentially associated with EAC survival based on disease stage. Future investigation of larger, diverse patient cohorts is essential to validate these findings. Our results may help inform the development of lifestyle-based interventions to improve EAC prognosis and quality of life.