Kristan J. Aronson

Considerations of circadian impact for defining 'shift work' in cancer studies : IARC Working Group Report.

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 subjects 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.

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.

Hypotheses for mechanisms linking shiftwork and cancer.

Shift work has been associated with various adverse health outcomes. In particular, there has been a recent flourish in investigating potential cancer risk associated with working night shifts and other shift schedules. Epidemiologic studies have revealed generally weak associations due to several methodological challenges such as lack of standard classifications of shift or night work. The field also has been hindered by a lack of clarity about the possible mechanisms by which shiftwork could have an effect on cancer risk. One possible mechanism is reduced production of melatonin caused by exposure to light at night. Although there is a growing body of evidence that provides some support for this mechanism, several other mechanisms also make sense from a biological point of view. Further, the relatively weak magnitude of the associations between light at night and melatonin level suggests that multiple factors may be operating along the pathway between shift work and adverse health consequences (including cancer risk). Here we propose four additional mechanisms that should be considered for a comprehensive investigation of these potential pathways. These are: phase shift; sleep disruption; lifestyle factors (such as poor quality diets, less physical activity and higher BMI); and lower vitamin D. Consideration of all these mechanisms is necessary in order to design effective preventative workplace strategies. In developed countries, approximately 20% of the population undertake shiftwork and, while we are unlikely to be able to eliminate shiftwork from current work practices, there are aspects of shiftwork that can be modified and there may be facets of individual susceptibility that we may be able to identify and target for prevention.

Organochlorines and breast cancer risk by receptor status, tumor size, and grade (Canada)

AbstractObjective: We evaluated the association between organochlorines and breast cancer subtype defined by the tumor characteristics: estrogen receptor status, progesterone receptor status, tumor size, and grade. Methods: A case–control study was conducted from 1995 to 1997 in Kingston and Toronto, Canada. Breast adipose tissue, taken from 217 cases and 213 biopsy controls frequency-matched on age, was analysed for 14 polychlorinated biphenyl (PCB) congeners and 10 pesticides. Results: Adjusting for age, geometric means of several organochlorines differed by estrogen receptor status and tumor grade (p < 0.05). Odds ratios (ORs) for each organochlorine relative to the common control group for breast cancers of differing subtype were compared using polytomous logistic regression. Although the ORs did not differ significantly by subtype, the ORs of PCBs and p, p′-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) were higher with risk of estrogen receptor-negative breast cancer than estrogen receptor-positive breast cancer. One of the most extreme differences was with DDE, where the OR for the association with risk of estrogen receptor-negative breast cancer was 2.4 (95% confidence interval (CI) 1.0–5.4) in the uppermost tertile relative to the lowest, whereas the corresponding OR for risk of estrogen receptor-positive breast cancer was 1.1 (95% CI 0.6–1.9). PCBs also tended to be more strongly positively associated with risk of larger and higher-grade tumors. Conclusions: The association between organochlorines and breast cancer risk did not significantly differ by subtype, but many PCBs were more strongly associated with tumors of poor prognosis.

Review of the Etiology of Breast Cancer with Special Attention to Organochlorines as Potential Endocrine Disruptors

Breast cancer is the most frequently diagnosed cancer among Canadian women, accounting for about 30% of all new cancer cases each year. Although the incidence of breast cancer has increased over the past 50 years, the cause of this rise is unknown. Risk factors for breast cancer may be classified into four broad categories: (1) genetic/familial, (2) reproductive/hormonal, (3) lifestyle, and (4) environmental. Established risk factors for breast cancer include older age, later age at first full-term pregnancy, no full-term pregnancies, postmenopausal obesity, and genetic factors. However, these known risk factors cannot account for the majority of cases. In the early 1990s, it was suggested that exposure to some environmental chemicals such as organochlorine compounds may play a causal role in the etiology of breast cancer through estrogen-related pathways. The relationship between organochlorines and breast cancer risk has been studied extensively in the past decade and more, and at this point there is no clear evidence to support a causal role of most organochlorine pesticides in the etiology of human breast cancer, but more evidence is needed to assess risk associated with polychlorinated biphenyls (PCBs). Future studies need to consider the combined effects of exposures, concentrate on vulnerable groups such as those with higher levels of exposure, only consider exposures occurring during the most etiologically relevant time periods, and more thoroughly consider gene–environment interactions.

Increased risk of breast cancer associated with long-term shift work in Canada

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.

Dietary patterns and risk of prostate cancer in Ontario, Canada

Dietary patterns reflect combinations of dietary exposures, and here we examine these in relation to prostate cancer risk. In a case‐control study, 80 incident primary prostate cancer cases and 334 urology clinic controls were enrolled from 1997 through 1999 in Kingston, Ontario, Canada. Food‐frequency questionnaires were completed prior to diagnosis and assessed intake in the 1‐year period 2–3 years prior to enrollment. Among controls, dietary intake was used in principal components analyses to identify patterns that were then evaluated with all subjects in relation to prostate cancer risk using unconditional logistic regression, controlling for age. Four dietary patterns were identified: Healthy Living, Traditional Western, Processed and Beverages. Increased prostate cancer risk is apparent in relation to the Processed pattern, composed of processed meats, red meats, organ meats, refined grains, white bread, onions and tomatoes, vegetable oil and juice, soft drinks and bottled water. The OR for the highest tertile compared to baseline is 2.75 (95% CI 1.40–5.39), with a dose–response pattern (trend test p < 0.0035). Our results suggest that a dietary pattern including refined grain products, processed meats and red and organ meats contributes to increased prostate cancer risk. Since dietary information was collected before subjects knew their diagnosis, recall bias was avoided.

LIGHT INTENSITY EXPOSURE, SLEEP DURATION, PHYSICAL ACTIVITY, AND BIOMARKERS OF MELATONIN AMONG ROTATING SHIFT NURSES

Long-term, night shiftwork has been identified as a potential carcinogenic risk factor. It is hypothesized that increased light at night exposure during shiftwork reduces melatonin production, which is associated with increased cancer risk. Sleep duration has been hypothesized to influence both melatonin levels and cancer risk, and it has been suggested that sleep duration could be used as a proxy for melatonin production. Finally, physical activity has been shown to reduce cancer risk, and laboratory studies indicate it may influence melatonin levels. A cross-sectional study of light exposure, sleep duration, physical activity, and melatonin levels was conducted among 61 female rotating shift nurses (work schedule: two 12 h days, two 12 h nights, five days off). Light intensity was measured using a light-intensity data logger, and sleep duration and physical activity were self-reported in a study diary and questionnaire. Melatonin concentrations were measured from urine and saliva samples. The characteristics of nurses working day and night shifts were similar. Light intensity was significantly higher during sleep for those working at night (p< 0.0001), while urinary melatonin levels following sleep were significantly higher among those working days (p = 0.0003). Mean sleep duration for nurses working during the day (8.27 h) was significantly longer than for those working at night (4.78 h, p< 0.0001). An inverse association (p = 0.002) between light exposure and urinary melatonin levels was observed; however, this was not significant when stratified by shift group. There was no significant correlation between sleep duration and melatonin, and no consistent relationship between physical activity and melatonin. Analysis of salivary melatonin levels indicated that the circadian rhythms of night workers were not altered, meaning peak melatonin production occurred at night. This study indicates that two nights of rotating shift work may not change the timing of melatonin production to the day among those working at night. Additionally, in this study, sleep duration was not correlated with urinary melatonin levels, suggesting it may not be a good proxy for melatonin production. (Author correspondence: anne.grundy@queensu.ca)

Incidence and mortality from breast cancer in the mama program for breast screening in Finland, 1973–1986

Background. A cohort of women enrolled in the Mama breast self‐examination‐(BSE) containing breast screening program in Finland from 1973 through 1975 (with BSE used for screening and mammography for diagnosis) was studied.

Oncogenic human papillomavirus infection and cervical lesions in aboriginal women of Nunavut, Canada

Background The high rate of cervical cancer among aboriginal women of northern Canada has prompted the search for more aggressive methods to augment Papanicolaou (Pap) screening in this population. Nearly all cervical cancers result from oncogenic human papillomavirus (HPV) infections. This has generated interest for incorporating HPV testing into the current screening program. Goals To determine the prevalence of oncogenic HPVs in Nunavut, and to assess the association between HPV and squamous intraepithelial lesions (SIL). Study Design A cross-sectional study was conducted on the Pap-screened populations in 19 communities of Nunavut, Canada. Liquid-based cytology was used to screen for SIL. HPV testing was performed using the Hybrid Capture II assay. Correlates of HPV infection and SIL were assessed by logistic regression with control for potential confounders. Results In 1290 women ages 13 to 79 years, the prevalence rate was 26% for oncogenic HPV and 6.9% for SIL. The odds ratio for the association between HPV and SIL was 37.9 (95% CI, 17.7–80.8) after multivariate adjustment. This association increased markedly with increasing viral load. More than 90% of the women with squamous intraepithelial lesions had positive test results for HPV. More than 75% of the women who had positive test results for HPV but negative test results for SIL were younger than 30 years. Conclusion The results of this study form the basis for further evaluation of the role that liquid-based cytology and HPV testing plays and will contribute to the strategy for cervical cancer prevention in Nunavut.