Inflammation contributes to breast cancer development through its effects on cell damage. This damage is usually dealt with by key genes involved in apoptosis and autophagy pathways.
We tested 206 ...single nucleotide polymorphisms (SNPs) in 54 genes related to inflammation, apoptosis and autophagy in a population-based breast cancer study of women of European (658 cases and 795 controls) and East Asian (262 cases and 127 controls) descent. Logistic regression was used to estimate odds ratios for breast cancer risk, and case-only analysis to compare breast cancer subtypes (defined by ER/PR/HER2 status), with adjustment for confounders. We assessed statistical interactions between the SNPs and lifestyle factors (smoking status, physical activity and body mass index).
Although no SNP was associated with breast cancer risk among women of European descent, we found evidence for an association among East Asians for rs1800925 (IL-13) and breast cancer risk (OR = 2.08; 95% CI: 1.32-3.28; p = 0.000779), which remained statistically significant after multiple testing correction (padj = 0.0350). This association was replicated in a meta-analysis of 4305 cases and 4194 controls in the Shanghai Breast Cancer Genetics Study (OR 1.12, 95% CI: 1.03-1.21, p = 0.011). Further, we found evidence of an interaction between rs7874234 (TSC1) and physical activity among women of East Asian descent.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectiveTo estimate the association between occupational polycyclic aromatic hydrocarbon (PAH) exposure and female breast cancer.MethodsLifetime work histories for 1130 cases and 1169 controls from ...British Columbia and Ontario (Canada) were assessed for PAH exposure using a job-exposure matrix based on compliance measurements obtained during US Occupational Safety and Health Administration workplace safety inspections.ResultsExposure to any level of PAHs was associated with an increased risk of breast cancer (OR=1.32, 95% CI: 1.10 to 1.59), as was duration at high PAH exposure (for >7.4 years: OR=1.45, 95% CI: 1.10 to 1.91; ptrend=0.01), compared with women who were never exposed. Increased risk of breast cancer was most strongly associated with prolonged duration at high occupational PAH exposure among women with a family history of breast cancer (for >7.4 years: OR=2.79, 95% CI: 1.25 to 6.24; ptrend<0.01).ConclusionsOur study suggests that prolonged occupational exposure to PAH may increase breast cancer risk, especially among women with a family history of breast cancer.
Relatively few population-based studies have explored the relationship and potential mechanisms between exposure to shift work and hypertension. The study objectives for this study were to determine ...1) if history of shift work was associated with increased rates of hypertension among working adults, and 2) if sleep quality mediated this relationship.
We conducted a population-based cohort study using data from Ontario respondents (aged 35-69 y) in the 2000-2001 Canadian Community Health Survey, which was linked to administrative health data housed at the Institute for Clinical Evaluative Sciences. Our sample included survey participants who were employed with no previous diagnosis of hypertension (n = 7420). During a 12-year follow-up window, we determined the time of hypertension diagnosis based on a previously validated algorithm; and explored the mediating effect of sleep quality using marginal structural effect models.
The study sample included 2079 shift workers and 5341 day workers. Shift workers reported less refreshing sleep, more trouble sleeping, and poorer sleep quality overall compared with day workers. In 12 years of follow-up, 31.3% of workers developed hypertension. History of shift work was associated with higher hypertension rates in both men (hazard ratio HR 1.21, 95% confidence interval CI 1.02-1.44) and women (HR 1.26, 95% CI 1.03-1.55). There was no evidence that these associations were mediated by past sleep quality.
History of shift work schedules is associated with increased rates of hypertension. Shift work disrupts sleep, but further longitudinal studies are needed to determine if sleep quality mediates the association between shift work and hypertension.
Il existe relativement peu d’études en population explorant le lien entre le travail par quarts et l’hypertension, ainsi que les mécanismes en cause. Notre étude avait pour but de déterminer si les antécédents de travail par quarts sont associés à une augmentation du risque d’hypertension chez les travailleurs adultes, et si la qualité du sommeil influe sur cette relation.
Nous avons mené une étude de cohorte en population à partir des réponses d’Ontariens de 35 à 69 ans obtenues dans l’Enquête sur la santé dans les collectivités canadiennes de 2000-2001, qui ont été couplées aux données administratives en santé de l’Institute for Clinical Evaluative Sciences. Notre échantillon comprenait les répondants qui occupaient un emploi et n’avaient jamais reçu de diagnostic d’hypertension (n = 7420). Pendant une période de suivi de 12 ans, nous avons déterminé le moment du diagnostic d’hypertension à l’aide d’un algorithme validé antérieurement et étudié l’effet de la qualité du sommeil au moyen de modèles structurels marginaux.
L’échantillon étudié comprenait 2 079 sujets travaillant par quarts et 5 341 sujets travaillant de jour. Les travailleurs par quarts ont rapporté avoir un sommeil moins réparateur, éprouver plus de difficulté à dormir et avoir un sommeil globalement de moins bonne qualité que les travailleurs de jour. Sur la période de suivi de 12 ans, 31,3 % des travailleurs ont développé une hypertension. Des antécédents de travail par quarts ont été associés à une fréquence plus élevée d’hypertension chez les hommes (rapport des risques instantanés RRI de 1,21; intervalle de confiance IC à 95 % : 1,02 à 1,44) et chez les femmes (RRI de 1,26; IC à 95 % : 1,03 à 1,55). Rien n’indique que la qualité du sommeil influait sur cette corrélation.
Des antécédents de travail par quarts sont associés à un risque accru d’hypertension. On sait que le travail par quarts perturbe le sommeil, mais d’autres études longitudinales sont nécessaires pour déterminer si la qualité du sommeil influe sur l’association entre le travail par quarts et l’hypertension.
Shift work has been identified as a risk factor for several cancer sites in recent years, with melatonin as a potential intermediate on the proposed causal pathway. This study examined the influence ...of nighttime light exposure on melatonin levels among 123 rotating shift nurses.
Nurses working a rotating shift schedule (two 12-hour days, two 12-hour nights, and five days off) were recruited and participated on a day and night shift in both the summer and winter seasons. Over each 48-hour study period, nurses wore a light data logger and provided two urine and four saliva samples.
Saliva measurements showed that the pattern of melatonin production did not differ between day and night shifts. Mean light exposure was significantly higher (P < 0.0001) when nurses were working at night, although peak melatonin levels (P = 0.65) and the daily change in melatonin levels (P = 0.80) were similar across day/night shifts. Multivariate analysis did not show an association between light exposure and melatonin levels when data from both shifts was combined; however, when data from the night shift was considered alone, a statistically significant inverse relationship between light and change in melatonin was observed (P = 0.04).
These results show that light exposure does not seem to be strongly related to reduced melatonin production among nurses on this rapidly rotating shift schedule.
Future research considering more extreme shift patterns or brighter lighting conditions could further clarify the relationship between light exposure and melatonin production in observational settings.
ObjectivesMechanisms 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.MethodsFemale 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.ResultsAmong 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.ConclusionsIn 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.
The purpose of this study is to elucidate the multiple pathways linking shift work exposure to cardiometabolic risk (CMR) through the intermediates of circadian disruption, sleep disturbances, and ...stress. A cross-sectional study was conducted at Kingston Health Sciences Center that included female hospital workers, 160 who worked a day-only schedule and 168 who worked rotating days and nights. Participants completed questionnaires, a clinical exam, and wore accelerometers to collect sleep data for 8 days. Participants also collected urine samples at each void during a 24-h collection period, on the day shift for day-only workers and the night shift for rotating shift workers, for cortisol and melatonin measures. We adapted and tested a conceptual model proposed by Knutsson and Boggild for circadian disruption, sleep, and stress mechanistic pathways linking shift work to CMR using structural equation modeling techniques. Status as a rotating shift worker was associated with increased circadian disruption of cortisol and melatonin production compared to day-only workers (P < .001). Increased circadian disruption was associated with an increased CMR (P = .01). Rotating shift work was associated with sleep disturbances (P = .002) and increased job stress (P < .001), but neither was associated with CMR. We conclude that rotating shift work is associated indirectly with increased CMR. This association is mediated by circadian disruption as indicated by attenuated melatonin and cortisol, and flatter cortisol curves.
Shift work causing circadian disruption is classified as a "probable carcinogen" and may contribute to the pathogenesis of hormone-sensitive cancers. This study investigated shift work exposure in ...relation to epithelial ovarian cancer (EOC) risk.
In a population-based case-control study with 496 EOC cases and 906 controls, lifetime occupational histories were collected and used to calculate cumulative years of shift work exposure, average number of night shifts per month, and average number of consecutive night shifts per month. ORs and 95% confidence intervals (CI) for associations with EOC risk were estimated using logistic regression. Associations were also examined according to chronotype and menopausal status.
More than half of the cases (53.4%) and controls (51.7%) worked evening and/or night shifts. There was no clear pattern of increasing EOC risk with increasing years of shift work; the adjusted OR of EOC comparing the highest shift work category versus never working shift work was 1.20 (95% CI, 0.89-1.63). This association was more pronounced among those self-identified as having a "morning" chronotype (OR, 1.64; 95% CI, 1.01-2.65). Associations did not greatly differ by menopausal status.
These results do not strongly demonstrate a relationship between shift work and EOC risk.
This study collected detailed shift work information and examined shift work patterns according to shift times and schedules. The findings highlight that chronotype should be considered in studies of shift work as an exposure.
Based on the idea that electric light at night might account for a portion of the high and rising risk of breast cancer worldwide, it was predicted long ago that women working a non-day shift would ...be at higher risk compared with day-working women. This hypothesis has been extended more recently to prostate cancer. On the basis of limited human evidence and sufficient evidence in experimental animals, in 2007 the International Agency for Research on Cancer (IARC) classified ‘shift work that involves circadian disruption’ as a probable human carcinogen, group 2A. A limitation of the epidemiological studies carried out to date is in the definition of ‘shift work.’ IARC convened a workshop in April 2009 to consider how ‘shift work’ should be assessed and what domains of occupational history need to be quantified for more valid studies of shift work and cancer in the future. The working group identified several major domains of non-day shifts and shift schedules that should be captured in future studies: (1) shift system (start time of shift, number of hours per day, rotating or permanent, speed and direction of a rotating system, regular or irregular); (2) years on a particular non-day shift schedule (and cumulative exposure to the shift system over the subject's working life); and (3) shift intensity (time off between successive work days on the shift schedule). The group also recognised that for further domains to be identified, more research needs to be conducted on the impact of various shift schedules and routines on physiological and circadian rhythms of workers in real-world environments.
Objectives Long-term night work has been suggested as a risk factor for breast cancer; however, additional studies with more comprehensive methods of exposure assessment to capture the diversity of ...shift patterns are needed. As well, few previous studies have considered the role of hormone receptor subtype. Methods Relationships between night shift work and breast cancer were examined among 1134 breast cancer cases and 1179 controls, frequency-matched by age in Vancouver, British Columbia, and Kingston, Ontario. Self-reported lifetime occupational histories were assessed for night shift work, and hormone receptor status obtained from tumour pathology records. Results With approximately one-third of cases and controls ever employed in night shift work, associations with duration demonstrated no relationship between either 0–14 or 15–29 years, while an association was apparent for ≥30 years (OR=2.21, 95% CI 1.14 to 4.31). This association with long-term night shift work is robust to alternative definitions of prolonged shift work, with similar results for both health and non-health care workers. Conclusions Long-term night shift work in a diverse mix of occupations is associated with increased breast cancer risk and not limited to nurses, as in most previous studies.
Experimental and epidemiologic studies suggest that light at night (LAN) exposure disrupts circadian rhythm, and this disruption may increase breast cancer risk. We investigated the potential ...association between residential outdoor LAN and breast cancer risk. A population-based case–control study was conducted in Vancouver, British Columbia and Kingston, Ontario, Canada with incident breast cancer cases, and controls frequency matched by age in the same region. This analysis was restricted to 844 cases and 905 controls who provided lifetime residential histories. Using time-weighted average duration at each home 5–20 years prior to study entry, two measures of cumulative average outdoor LAN were calculated using two satellite data sources. Logistic regression was used to estimate the relationship between outdoor LAN and breast cancer risk, considering interactions for menopausal status and night shift work. We found no association between residential outdoor LAN and breast cancer for either measure of LAN OR comparing highest vs. lowest tertile (DNB) = 0.95, 95% CI 0.70–1.27. We also found no association when considering interactions for menopausal status and past/current night work status. These findings were robust to changes to years of residential data considered, residential mobility, and longer exposure windows. Our findings are consistent with studies reporting that outdoor LAN has a small effect or no effect on breast cancer risk.
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