Lin Fritschi

Leukemia Risk Associated With Low-Level Benzene Exposure

Background: Men who were part of an Australian petroleum industry cohort had previously been found to have an excess of lympho-hematopoietic cancer. Occupational benzene exposure is a possible cause of this excess. Methods: We conducted a case-control study of lympho-hematopoietic cancer nested within the existing cohort study to examine the role of benzene exposure. Cases identified between 1981 and 1999 (N = 79) were age-matched to 5 control subjects from the cohort. We estimated each subject’s benzene exposure using occupational histories, local site-specific information, and an algorithm using Australian petroleum industry monitoring data. Results: Matched analyses showed that the risk of leukemia was increased at cumulative exposures above 2 ppm-years and with intensity of exposure of highest exposed job over 0.8 ppm. Risk increased with higher exposures; for the 13 case-sets with greater than 8 ppm-years cumulative exposure, the odds ratio was 11.3 (95% confidence interval = 2.85-45.1). The risk of leukemia was not associated with start date or duration of employment. The association with type of workplace was explained by cumulative exposure. There is limited evidence that short-term high exposures carry more risk than the same amount of exposure spread over a longer period. The risks for acute nonlymphocytic leukemia and chronic lymphocytic leukemia were raised for the highest exposed workers. No association was found between non-Hodgkin lymphoma or multiple myeloma and benzene exposure, nor between tobacco or alcohol consumption and any of the cancers. Conclusions: We found an excess risk of leukemia associated with cumulative benzene exposures and benzene exposure intensities that were considerably lower than reported in previous studies. No evidence was found of a threshold cumulative exposure below which there was no risk.

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.

Physical Activity and Risks of Proximal and Distal Colon Cancers: A Systematic Review and Meta-analysis

BACKGROUND Although there is convincing epidemiological evidence that physical activity is associated with a reduced risk of colon cancer, it is unclear whether physical activity is differentially associated with the risks of proximal colon and distal colon cancers. We conducted a systematic review and meta-analysis to investigate this issue. METHODS MEDLINE and EMBASE were searched for English-language cohort and case-control studies that examined associations between physical activity and the risks of proximal colon and distal colon cancers. A random-effects meta-analysis was conducted to estimate the summary relative risks (RRs) for the associations between physical activity and the risks of the two cancers. All statistical tests were two-sided. RESULTS A total of 21 studies met the inclusion criteria. The summary relative risk of the main results from these studies indicated that the risk of proximal colon cancer was 27% lower among the most physically active people compared with the least active people (RR = 0.73, 95% confidence interval [CI] = 0.66 to 0.81). An almost identical result was found for distal colon cancer (RR = 0.74, 95% CI = 0.68 to 0.80). CONCLUSION The results of this systematic review and meta-analysis suggest that physical activity is associated with a reduced risk of both proximal colon and distal colon cancers, and that the magnitude of the association does not differ by subsite. Given this finding, future research on physical activity and colon cancer should focus on other aspects of the association that remain unclear, such as whether sedentary behavior and nonaerobic physical activity are associated with the risk of colon cancer.

Reliability of an expert rating procedure for retrospective assessment of occupational exposures in community-based case-control studies

The most daunting problem in community-based studies of occupational cancer is retrospective exposure assessment. To avoid the error involved in using job title as the exposure variable or self-report of exposure, our team developed an approach based on expert judgment applied to job descriptions obtained by interviewers. A population-based case-control study of cancer and occupation was carried out in Montreal between 1979 and 1986, and over 4,000 job histories were assessed by our team of experts. The job histories of these subjects were evaluated, by consensus, by a team of chemist/hygienists for evidence of exposure to a list of 294 workplace chemicals. In order to evaluate the reliability of this exposure assessment procedure, four years after the rating was completed, we selected 50 job histories at random and had two members of the expert team carry out the same type of coding, blind to the original ratings for these jobs. For 25 job histories, comprising 94 distinct jobs, the pair worked as a consensus panel; for the other 25, comprising 92 distinct jobs, they worked independently. Statistical comparisons were made between the new ratings and the old. Among those rated by consensus, the marginal distribution of exposure prevalence was almost identical between old and new. The weighted kappa for agreement was 0.80. Among items for which both ratings agreed that there had been exposure, there was good agreement on the frequency, concentration, and route of contact. When the two raters worked independently, the levels of agreement between them and between each of them and the original rating was good (kappas around 0.70), though not as high as when they worked together. It is concluded that high levels of reliability are attainable for retrospective exposure assessment by experts.

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.

Comparison of occupational exposure using three different methods: hygiene panel, job exposure matrix (JEM), and self reports.

This study was undertaken to compare the agreement of occupational exposure assessment by a panel of occupational hygienists with a job exposure matrix and self-reported exposures in a community-based case-control study. We also investigated the intra-rater reliability and degree of attenuation of the hypothetical odds ratio of the panel in retrospective chemical exposure assessment. A panel of three occupational hygienists was recruited to assess exposure to chemicals for 5,620 jobs. The agreement between the panel, a job exposure matrix (FINJEM), and the self-reported exposures was then assessed. A further 172 jobs were resubmitted to the panel to assess intra-rater reliability. The kappa for intra-rater reliability ranged from 0.60-0.71. The agreement between the panel and FINJEM ranged from 0.07 to 0.46 (for similar exposures), and agreement between the panel and among the self-reports ranged from 0.00 to 0.48. Agreement between hygienists when rating exposure to the same chemical ranged from 0.48 to 0.57. Based on these findings, the degree of exposure misclassification by the panel where the true odds ratio was 2 would result in the observed odds ratio ranging between 1.70 and 1.88. The results indicated good intra-rater reliability for the hygiene panel. However, the agreement among the panel, FINJEM, and self-reported exposures was found to be only poor to fair. The attenuation of the odds ratios due to exposure misclassification by the panel was variable and dependent upon the exposure.

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.

Non-cancer mortality among people diagnosed with cancer (Australia).

ObjectiveTo investigate whether people diagnosed with cancer have an increased risk of death from non-cancer causes compared to the general population.MethodsThe non-cancer mortality of people diagnosed with cancer in Queensland (Australia) between 1982 and 2002 who had not died before 1 January 1993 was compared to the mortality of the total Queensland population, matching by age group and sex, and reporting by standardised mortality ratios.ResultsCompared to the non-cancer mortality in the general population, cancer patients (all cancers combined) were nearly 50% more likely to die of non-cancer causes (SMR = 149.9, 95% CI = [147–153]). This varied by cancer site. Overall melanoma patients had significantly lower non-cancer mortality, female breast cancer patients had similar non-cancer mortality to the general population, while increased non-cancer mortality risks were observed for people diagnosed with cervical cancer, colorectal cancer, prostate cancer, non-Hodgkin lymphoma and lung cancer.ConclusionsAlthough cancer-specific death rates underestimate the mortality directly associated with a diagnosis of cancer, quantifying the degree of underestimation is difficult due to various competing explanations. There remains an important role for future research in understanding the causes of morbidity among cancer survivors, particularly those looking at both co-morbid illnesses and reductions in quality of life.

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.

Malignant pleural and peritoneal mesotheliomas in former miners and millers of crocidolite at Wittenoom, Western Australia

Aims: To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2000, and to compare this with earlier predictions. Methods: A group of 6493 men and 415 women who had worked at the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2000. Results: The cumulative number of mesotheliomas up to 2000 was 235 in men (202 pleural, 33 peritoneal) and seven (all pleural) in women. There had been 231 deaths with mesothelioma (9% of known deaths). Conclusions: The number of deaths in men with mesothelioma between 1987 and 2000 was at the low end of the predictions made earlier based on the number of cases to 1986. If this trend continues, it is predicted that about another 110 deaths with mesothelioma will occur in men by 2020.