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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.
RESUMO
Objectives: Second-hand smoke (SHS) exposure causes >600,000 deaths annually worldwide, however, information regarding SHS exposure in Lao People's Democratic Republic (Lao PRD) is limited; we report SHS exposure prevalence at home, inside workplaces, and indoor public spaces in Lao PDR. Methods: Data were from the 2015 Lao National Adult Tobacco Survey, a nationally representative sample of 7,562 participants aged ≥15 years recruited through a stratified 2-stage cluster sampling approach. Results: 88.3% (83.9% of non-smokers) reported SHS exposure at home and 63.0% (54.0% of non-smokers) at workplaces. Among non-smokers, women had greater exposure at home than men (86.6 vs. 77.0%). Lower education levels were associated with exposure at home or the workplace. 99.2% reported SHS exposure at any public place; specifically for restaurants/food stores 57.7%, government offices 56.2%, public transport 31.6%, and health care facilities 11.7%. Conclusion: SHS exposure at home and workplace in Lao PDR is among the highest in South-East Asia. Comprehensive smoke-free policies at government-owned workplaces and facilities, stricter enforcement of these smoke-free policies, and strategies to encourage smoke-free environments at homes and in public places are urgently needed.
