Background Rotating night shift work imposes circadian strain and is linked to the risk of several chronic diseases. Purpose To examine associations between rotating night shift work and all-cause; ...cardiovascular disease (CVD); and cancer mortality in a prospective cohort study of 74,862 registered U.S. nurses from the Nurses’ Health Study. Methods Lifetime rotating night shift work (defined as ≥3 nights/month) information was collected in 1988. During 22 years (1988–2010) of follow-up, 14,181 deaths were documented, including 3,062 CVD and 5,413 cancer deaths. Cox proportional hazards models estimated multivariable-adjusted hazard ratios (HRs) and 95% CIs. Results All-cause and CVD mortality were significantly increased among women with ≥5 years of rotating night shift work, compared to women who never worked night shifts. Specifically, for women with 6–14 and ≥15 years of rotating night shift work, the HRs were 1.11 (95% CI=1.06, 1.17) and 1.11 (95% CI=1.05, 1.18) for all-cause mortality and 1.19 (95% CI=1.07, 1.33) and 1.23 (95% CI=1.09, 1.38) for CVD mortality. There was no significant association between rotating night shift work and all-cancer mortality (HR≥15years =1.08, 95% CI=0.98, 1.19) or mortality of any individual cancer, with the exception of lung cancer (HR≥15years =1.25, 95% CI=1.04, 1.51). Conclusions Women working rotating night shifts for ≥5 years have a modest increase in all-cause and CVD mortality; those working ≥15 years of rotating night shift work have a modest increase in lung cancer mortality. These results add to prior evidence of a potentially detrimental effect of rotating night shift work on health and longevity.
Circadian disruption is a probable human carcinogen. From the eastern to western border of a time zone, social time is equal, whereas solar time is progressively delayed, producing increased ...discrepancies between individuals' social and biological circadian time. Accordingly, western time zone residents experience greater circadian disruption and may be at an increased risk of cancer.
We examined associations between the position in a time zone and age-standardized county-level incidence rates for total cancers combined and 23 specific cancers by gender using the data of the Surveillance, Epidemiology, and End Results Program (2000-2012), including four million cancer diagnoses in white residents of 607 counties in 11 U.S. states. Log-linear regression was conducted, adjusting for latitude, poverty, cigarette smoking, and state. Bonferroni-corrected
values were used as the significance criteria.
Risk increased from east to west within a time zone for total and for many specific cancers, including chronic lymphocytic leukemia (both genders) and cancers of the stomach, liver, prostate, and non-Hodgkin lymphoma in men and cancers of the esophagus, colorectum, lung, breast, and corpus uteri in women.
Risk increased from the east to the west in a time zone for total and many specific cancers, in accord with the circadian disruption hypothesis. Replications in analytic epidemiologic studies are warranted.
Our findings suggest that circadian disruption may not be a rare phenomenon affecting only shift workers, but is widespread in the general population with broader implications for public health than generally appreciated.
.
Very few studies have examined sleep duration in relation to cancer incidence with the exception of breast cancer.
We assessed the associations between sleep duration and incidences of total and 18 ...site-specific cancers in the NIH-AARP Health and Diet Study cohort, with 173,327 men and 123,858 women aged 51-72 years at baseline. Self-reported sleep duration categories were assessed via questionnaire. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), using 7-8 hours/night as the reference.
We observed a significantly increased risk of stomach cancer among male short sleepers (multivariable HR5-6 vs. 7-8 hours = 1.29; 95%CI: 1.05, 1.59; Ptrend = 0.03). We also observed suggestive associations in either short or long sleepers, which did not reach overall significance (Ptrend >0.05), including increased risks in male short sleepers for cancers of head and neck (HR<5vs.7-8 hours = 1.39; 95%CI:1.00-1.95), bladder (HR5-6vs.7-8 hours = 1.10; 95%CI:1.00-1.20), thyroid (HR<5 vs. 7-8 hours = 2.30; 95%CI:1.06, 5.02), Non-Hodgkin Lymphoma (NHL) (HR5-6vs.7-8 hours = 1.17; 95%CI:1.02-1.33), and myeloma (HR<5vs.7-8 hours = 2.06; 95%CI:1.20-3.51). In women, the suggestive associations include a decreased total cancer risk (HR<5vs.7-8 hours = 0.9; 95%CI:0.83-0.99) and breast cancer risk (HR<5vs.7-8 hours = 0.84; 95%CI:0.71-0.98) among short sleepers. A decreased ovarian cancer risk (HR≥ 9 vs. 7-8 hours = 0.50; 95%CI:0.26-0.97) and an increased NHL risk (HR≥ 9 vs. 7-8 hours = 1.45; 95%CI:1.00-2.11) were observed among long sleepers.
In an older population, we observed an increased stomach cancer risk in male short sleepers and suggestive associations with short or long sleep duration for many cancer risks in both genders.
Abstract
Tobacco use, hypertension, hyperglycemia, overweight, and inactivity are leading causes of overall and cardiovascular disease (CVD) mortality worldwide, yet the relevant metabolic ...alterations responsible are largely unknown. We conducted a serum metabolomic analysis of 620 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985–2013). During 28 years of follow-up, there were 435 deaths (197 CVD and 107 cancer). The analysis included 406 known metabolites measured with ultra-high-performance liquid chromatography/mass spectrometry–gas chromatography/mass spectrometry. We used Cox regression to estimate mortality hazard ratios for a 1-standard-deviation difference in metabolite signals. The strongest associations with overall mortality were N-acetylvaline (hazard ratio (HR) = 1.28; P < 4.1 × 10−5, below Bonferroni statistical threshold) and dimethylglycine, 7-methylguanine, C-glycosyltryptophan, taurocholate, and N-acetyltryptophan (1.23 ≤ HR ≤ 1.32; 5 × 10−5 ≤ P ≤ 1 × 10−4). C-Glycosyltryptophan, 7-methylguanine, and 4-androsten-3β,17β-diol disulfate were statistically significantly associated with CVD mortality (1.49 ≤ HR ≤ 1.62, P < 4.1 × 10−5). No metabolite was associated with cancer mortality, at a false discovery rate of <0.1. Individuals with a 1-standard-deviation higher metabolite risk score had increased all-cause and CVD mortality in the test set (HR = 1.4, P = 0.05; HR = 1.8, P = 0.003, respectively). The several serum metabolites and their composite risk score independently associated with all-cause and CVD mortality may provide potential leads regarding the molecular basis of mortality.
The contribution of common genetic variation to one or more established smoking behaviors was investigated in a joint analysis of two genome wide association studies (GWAS) performed as part of the ...Cancer Genetic Markers of Susceptibility (CGEMS) project in 2,329 men from the Prostate, Lung, Colon and Ovarian (PLCO) Trial, and 2,282 women from the Nurses' Health Study (NHS). We analyzed seven measures of smoking behavior, four continuous (cigarettes per day CPD, age at initiation of smoking, duration of smoking, and pack years), and three binary (ever versus never smoking, < or = 10 versus > 10 cigarettes per day CPDBI, and current versus former smoking). Association testing for each single nucleotide polymorphism (SNP) was conducted by study and adjusted for age, cohabitation/marital status, education, site, and principal components of population substructure. None of the SNPs achieved genome-wide significance (p<10(-7)) in any combined analysis pooling evidence for association across the two studies; we observed between two and seven SNPs with p<10(-5) for each of the seven measures. In the chr15q25.1 region spanning the nicotinic receptors CHRNA3 and CHRNA5, we identified multiple SNPs associated with CPD (p<10(-3)), including rs1051730, which has been associated with nicotine dependence, smoking intensity and lung cancer risk. In parallel, we selected 11,199 SNPs drawn from 359 a priori candidate genes and performed individual-gene and gene-group analyses. After adjusting for multiple tests conducted within each gene, we identified between two and five genes associated with each measure of smoking behavior. Besides CHRNA3 and CHRNA5, MAOA was associated with CPDBI (gene-level p<5.4x10(-5)), our analysis provides independent replication of the association between the chr15q25.1 region and smoking intensity and data for multiple other loci associated with smoking behavior that merit further follow-up.
Patients with head and neck cancer (HNC) undergoing radiation therapy (RT) often experience sleep disturbances that may contribute to oral mucositis (OM) and quality of life (QOL).
Patients with HNC ...treated with RT at a single institution were examined. Sleep questionnaires were given on the first day of RT to assess for insomnia and obstructive sleep apnea (OSA). Patient-reported QOL and oral mucositis were assessed during RT. Associations between insomnia and OSA with QOL were assessed using the Mann-Whitney U test. Linear mixed models assessed associations with OM.
Among 87 patients, 34 patients (39%) had subthreshold or greater insomnia and 47 patients (54%) screened positive for OSA. Upon RT completion, patients with subthreshold or greater insomnia had worse physical function (
= 0.005), fatigue (
= 0.01), insomnia (
< 0.001), and sticky saliva (
= 0.002). Patients screening positive for OSA had worse physical function (
= 0.01), sticky saliva (
= 0.02), fatigue (
= 0.007), insomnia (
= 0.009), and pain (
= 0.005). Upon linear mixed model evaluation, subthreshold or greater insomnia (
= 0.01) and positive OSA screen (
= 0.002) were associated with worse OM.
Insomnia and OSA are highly prevalent in patients with HNC undergoing RT. These sleep disturbances are associated with worse QOL and OM during treatment.
Body mass is inversely related to breast cancer risk among premenopausal women. Leptin, an essential cytokine regulating food intake, energy expenditure, glucose, and fat metabolism may be part of ...the mechanistic pathway. We investigated 50 tagging and candidate SNPs in the leptin (
LEP
) and leptin receptor (
LEPR
) genes for associations with premenopausal breast cancer incidence using 405 cases and 810 controls nested within the Nurses’ Health Study II. We also examined associations between these SNPs and circulating leptin (among 910 women) and breast cancer grade (among 267 patients). Permutation tests were performed to adjust for multiple testing. We did not detect a significant association between SNPs in the
LEP
or
LEPR
gene and either breast cancer incidence or plasma leptin levels. Among cases, 14 SNPs of the
LEPR
gene were significantly associated with cancer grade, and rs1137101 (Q223R) survived multiple testing adjustment (adjusted
P
= 0.04). The G carriers of rs1137101 were more likely to have poorly differentiated than well-differentiated cancers. Our data suggest that common genetic variation in the
LEP
or
LEPR
gene has no strong association with premenopausal breast cancer risk. The
LEPR
gene might be associated with breast cancer grade.
Patient-reported quality of life (QoL) metrics, frailty status, and physical functioning are emerging concepts in head and neck cancer (HNC) with implications on both treatment decision-making and ...prognosis. The impact of treatment-related functional decline on QoL and frailty has not been well-characterized in HNC and was the focus of this investigation.
Patients who underwent radiation therapy for HNC from 2018 to 2020 were evaluated as a prospective observational cohort. Functional decline, QoL, and the frailty phenotype were measured via the Short Physical Performance Battery (SPPB), European Organization for Research and Treatment of Cancer (EORTC) qlq-C30, and Fried Frailty index, respectively.
A total of 106 HNC patients were included, 75 of which received concurrent chemoradiation therapy (CCRT) and 31 received radiation alone, both with and without surgery. There was a decrease in SPPB overall (
< 0.001) from the beginning to the end of treatment in the CCRT group but not the radiation group (
= 0.43). Change in overall SPPB points following treatment correlated with the decline in physical QoL for both groups (
< 0.05) as well as transition frail status in the CCRT group (
< 0.001) with a trend in the radiation group (
= 0.08).
Change in SPPB correlates with QoL and transition to frailty status in patients undergoing definitive CCRT for HNC with similar trends in those receiving radiation alone. Decline in SPPB could potentially be useful in identification of those who may benefit from rehabilitation in future studies.
The DNA repair pathways help to maintain genomic integrity and therefore genetic variation in the pathways could affect the propensity to develop cancer. Selected germline single nucleotide ...polymorphisms (SNPs) in the pathways have been associated with esophageal cancer and gastric cancer (GC) but few studies have comprehensively examined the pathway genes. We aimed to investigate associations between DNA repair pathway genes and risk of esophageal squamous cell carcinoma (ESCC) and GC, using data from a genome-wide association study in a Han Chinese population where ESCC and GC are the predominant cancers. In sum, 1942 ESCC cases, 1758 GC cases and 2111 controls from the Shanxi Upper Gastrointestinal Cancer Genetics Project (discovery set) and the Linxian Nutrition Intervention Trials (replication set) were genotyped for 1675 SNPs in 170 DNA repair-related genes. Logistic regression models were applied to evaluate SNP-level associations. Gene- and pathway-level associations were determined using the resampling-based adaptive rank-truncated product approach. The DNA repair pathways overall were significantly associated with risk of ESCC (P = 6.37 × 10(-4)), but not with GC (P = 0.20). The most significant gene in ESCC was CHEK2 (P = 2.00 × 10(-6)) and in GC was CLK2 (P = 3.02 × 10(-4)). We observed several other genes significantly associated with either ESCC (SMUG1, TDG, TP53, GTF2H3, FEN1, POLQ, HEL308, RAD54B, MPG, FANCE and BRCA1) or GC risk (MRE11A, RAD54L and POLE) (P < 0.05). We provide evidence for an association between specific genes in the DNA repair pathways and the risk of ESCC and GC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.
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