Jennifer Girschik

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.

Validation of self-reported sleep against actigraphy

Background Self-report remains the most practical and cost-effective method for epidemiologic sleep studies involving large population-based samples. Several validated questionnaires have been developed to assess sleep, but these tools are lengthy to administer and may be impractical for epidemiologic studies. We examined whether a 3-item sleep questionnaire, similar to those typically used in epidemiologic studies, closely corresponded with objective measures of sleep as assessed using actigraphy monitoring. Methods Eligible participants were Western Australian women aged 18 to 80 years. Participants completed a sleep questionnaire, wore a wrist actigraph for 7 nights, and completed a brief daily sleep log. Objective actigraphy measurements for 56 participants were summarized by mean and mode and compared with the subjective reports, using weighted kappa and delta. Results Data collected from the questionnaire showed poor agreement with objectively measured sleep, with kappas ranging from −0.19 to 0.14. Conclusions Our results indicate that sleep questions typically used in epidemiologic studies do not closely correspond with objective measures of sleep as assessed using actigraphy. The findings have implications for studies that have used such sleep questions. A means of appropriately measuring sleep as a risk factor in epidemiologic studies remains to be determined.

OccIDEAS: Retrospective Occupational Exposure Assessment in Community-Based Studies Made Easier

Assessing occupational exposure in retrospective community-based case-control studies is difficult as measured exposure data are very seldom available. The expert assessment method is considered the most accurate way to attribute exposure but it is a time consuming and expensive process and may be seen as subjective, nonreproducible, and nontransparent. In this paper, we describe these problems and outline our solutions as operationalized in a web-based software application (OccIDEAS). The novel aspects of OccIDEAS are combining all steps in the assessment into one software package; enmeshing the process of assessment into the development of questionnaires; selecting the exposure(s) of interest; specifying rules for exposure assignment; allowing manual or automatic assessments; ensuring that circumstances in which exposure is possible for an individual are highlighted for review; providing reports to ensure consistency of assessment. Development of this application has the potential to make high-quality occupational assessment more efficient and accessible for epidemiological studies.

Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study

Background:Patients with chronic lymphocytic leukaemia (CLL) are known to have increased risks of second cancer. The incidence of second cancers after CLL has not been reported in detail for Australia, a country with particularly high levels of ultraviolet radiation (UVR).Methods:The study cohort comprised of all people diagnosed with a primary CLL between 1983 and 2005 in Australia. Standardised incidence ratios (SIRs) and standardised mortality ratios (SMRs) were calculated using Australian population rates.Results:Overall, the risk of any second incident cancer was more than double that of the general population (SIR=2.17, 95% confidence interval (CI)=2.07, 2.27) and remained elevated for at least 9 years after CLL. Risks were increased for many cancers, particularly melanoma (SIR=7.74, 95% CI=6.85, 8.72). The risk of melanoma increased at younger ages, but was constant across >9 years of follow-up. Chronic lymphocytic leukaemia patients also had an increased risk of death because of melanoma (SMR=4.79, 95% CI=3.83, 5.90) and non-melanoma skin cancer (NMSC; SMR=17.0, 95% CI=14.4, 19.8), suggesting that these skin cancers may be more aggressive in CLL patients.Conclusion:We speculate that a shared risk factor, such as general immune suppression, modulated by UVR exposure may explain the increased risk of melanoma and NMSC in CLL patients.

The MTHFR C677T and ΔDNMT3B C-149T polymorphisms confer different risks for right- and left-sided colorectal cancer.

Etiological risk factors for proximal (right‐sided) colon cancers may be different to those of distal colon and rectal (left‐sided) cancers if these tumors develop along distinct pathways. The CpG Island Methylator Phenotype (CIMP+) occurs in approximately 15% of colorectal cancers (CRC) and predominantly in the proximal colon. CIMP+ tumors have frequent methylation of gene promoter regions and increased tissue folate levels. The aim here was to determine whether polymorphisms in 2 genes involved in cellular methyl group metabolism were associated with different risks for right‐ and left‐sided CRC. This population‐based case–control study involved 859 incident cases of CRC and 973 sex and age‐matched controls. Information on dietary folate and alcohol intake was obtained from food frequency questionnaires and information on the anatomical site of tumors from pathology reports. DNA was collected using FTA cards and genotyping performed for the MTHFR C677T and ΔDNMT3B C‐149T polymorphisms. The MTHFR 677 T allele was associated with increased risk for proximal colon cancer (adjusted odds ratio, AOR = 1.29) but decreased risk for distal cancers (AOR = 0.87). The increased risk for proximal cancers was especially pronounced in older individuals (AOR = 1.49) and those with a low folate diet (AOR = 1.67) or high alcohol consumption (AOR = 1.90). The ΔDNMT3B‐149 TT genotype was protective against proximal colon cancers (AOR = 0.65), but showed no association with the risk of distal colon and rectal cancers (AOR = 1.02). Epidemiological studies on dietary and genetic risk factors for CRC should take into account these may confer different risks for right‐ and left‐sided tumors.

Merkel cell carcinoma in Western Australia: a population-based study of incidence and survival.

Background  Merkel cell carcinoma (MCC) is an uncommon but aggressive cutaneous skin cancer. Even with the appropriate treatment, MCC is prone to recurrence, and metastases are common. Exposure to ultraviolet radiation has been suggested as contributing towards the development of MCC. MCC has not been extensively investigated in Australia, even though Australia has the highest incidence of sun‐related cancers in the world.

The Association Between Different Night Shiftwork Factors and Breast Cancer: a Case–Control Study

Background:Research on the possible association between shiftwork and breast cancer is complicated because there are many different shiftwork factors, which might be involved including: light at night, phase shift, sleep disruption and changes in lifestyle factors while on shiftwork (diet, physical activity, alcohol intake and low sun exposure).Methods:We conducted a population-based case–control study in Western Australia from 2009 to 2011 with 1205 incident breast cancer cases and 1789 frequency age-matched controls. A self-administered questionnaire was used to collect demographic, reproductive, and lifestyle factors and lifetime occupational history and a telephone interview was used to obtain further details about the shiftwork factors listed above.Results:A small increase in risk was suggested for those ever doing the graveyard shift (work between midnight and 0500 hours) and breast cancer (odds ratio (OR)=1.16, 95% confidence interval (CI)=0.97–1.39). For phase shift, we found a 22% increase in breast cancer risk (OR=1.22, 95% CI=1.01–1.47) with a statistically significant dose–response relationship (P=0.04). For the other shiftwork factors, risks were marginally elevated and not statistically significant.Conclusion:We found some evidence that some of the factors involved in shiftwork may be associated with breast cancer but the ORs were low and there were inconsistencies in duration and dose–response relationships.

Deaths from non-melanoma skin cancer in Western Australia

ObjectivesNon-melanoma skin cancer (NMSC) is common, slow growing, and rarely metastasizes. However, there are still nearly 400 deaths from NMSC in Australia annually. We aimed to investigate the accuracy of NMSC death coding and to describe the characteristics of these deaths and the potential for prevention.MethodsHistology reports for all deaths coded as NMSC (ICD-10 C44.0-C44.9) by the Western Australian Cancer Registry for the years 1996–2005 were reviewed for type of cancer, body site (primary tumor and metastases), and level of available documentation.ResultsOf 368 deaths recorded as being due to NMSC only 3 were found to be miscoded. An additional 53 deaths contained inadequate information to confirm NMSC as the cause of death. Of the confirmed cases, 219 were due to squamous cell carcinoma, 53 to Merkel cell carcinomas, and 40 to other skin cancers. Cases were mainly males and were elderly. Most of the primary squamous and Merkel cell carcinomas were in areas of maximum sun exposure (face, ears, and hands, and scalp in males).ConclusionsMisclassification of NMSC deaths in WA was minimal. The majority of NMSC deaths were due to squamous cell carcinomas; had primary sites associated with significant sun exposure; and occurred in older men.

Beliefs and perceptions about the causes of breast cancer: a case-control study

BackgroundAttributions of causality are common for many diseases, including breast cancer. The risk of developing breast cancer can be reduced by modifications to lifestyle and behaviours to minimise exposure to specific risk factors, such as obesity. However, these modifications will only occur if women believe that certain behaviours/lifestyle factors have an impact on the development of breast cancer.MethodThe Breast Cancer, Environment and Employment Study is a case-control study of breast cancer conducted in Western Australia between 2009 and 2011. As part of the study 1109 women with breast cancer and 1633 women without the disease completed a Risk Perception Questionnaire in which they were asked in an open-ended question for specific cause/s to the development of breast cancer in themselves or in others. The study identified specific causal beliefs, and assessed differences in the beliefs between women with and without breast cancer.ResultsThe most common attributions in women without breast cancer were to familial or inherited factors (77.6%), followed by lifestyle factors, such as poor diet and smoking (47.1%), and environmental factors, such as food additives (45.4%). The most common attributions in women with breast cancer were to mental or emotional factors (46.3%), especially stress, followed by lifestyle factors (38.6%) and physiological factors (37.5%), particularly relating to hormonal history.ConclusionsWhile the majority of participants in this study provided one or more causal attributions for breast cancer, many of the reported risk factors do not correspond to those generally accepted by the scientific community. These misperceptions could be having a significant impact on the success of prevention and early detection programs that seek to minimise the pain and suffering caused by this disease. In particular, women who have no family history of the disease may not work to minimise their exposure to the modifiable risk factors.

The collective impact of rare diseases in Western Australia: an estimate using a population-based cohort

Purpose:It has been argued that rare diseases should be recognized as a public health priority. However, there is a shortage of epidemiological data describing the true burden of rare diseases. This study investigated hospital service use to provide a better understanding of the collective health and economic impacts of rare diseases.Methods:Novel methodology was developed using a carefully constructed set of diagnostic codes, a selection of rare disease cohorts from hospital administrative data, and advanced data-linkage technologies. Outcomes included health-service use and hospital admission costs.Results:In 2010, cohort members who were alive represented approximately 2.0% of the Western Australian population. The cohort accounted for 4.6% of people discharged from hospital and 9.9% of hospital discharges, and it had a greater average length of stay than the general population. The total cost of hospital discharges for the cohort represented 10.5% of 2010 state inpatient hospital costs.Conclusions:This population-based cohort study provides strong new evidence of a marked disparity between the proportion of the population with rare diseases and their combined health-system costs. The methodology will inform future rare-disease studies, and the evidence will guide government strategies for managing the service needs of people living with rare diseases.Genet Med advance online publication 22 September 2016