Physical Activity, Step Counts, and Grip Strength in the Chinese Children and Families Cohort Study.

OBJECTIVES: This paper describes the development of a physical activity questionnaire (PAQ) designed for Chinese adolescents and their mothers in urban and rural settings, and reports on results of the PAQ, pedometry, and hand grip dynamometry from the Chinese Children and Families Cohort Study pilot investigation (CFCS). METHODS: As part of a pilot investigation to evaluate the feasibility to follow-up and obtain detailed nutrition, dietary, physical activity, and ultraviolet radiation (UVR) data from CFCS participants, data were collected in 2013 for 93 adolescent/mother pairs from a rural (n = 41) and an urban site (n = 52) in two provinces. Respondents were asked to wear a pedometer for seven days (Omron HJ-151), use a Takei Digital Grip Strength Dynamometer on (each hand; three trials; two separate days), and complete a 39 item, eight domain PAQ covering the past year. Self-reported physical activity (PA) was linked to metabolic equivalent of task (MET) scores in kcal/kg/hr and used to calculate METs for different domains of PA and intensity categories. RESULTS: Compliance was high (95%) in this measurement protocol administered by health staff during a series of data collection efforts at home and local clinics or health centers. Step counts were highly variable, averaging between 5000 and 10000 per day with somewhat higher step counts in rural adolescent boys. Maximum grip strength (Kgs) was greater in children (Mean = 36.5, SE = 0.8) than mothers (Mean = 28.8, SE = 0.8) and similar in the urban (Mean = 29.6, SE = 0.6) compared to the rural (Mean = 29.6, SE = 0.5) communities overall. Grip strength, step counts, and measures of time spent in different activities or activity intensities were uncorrelated. CONCLUSION: Device and question-based measurement of PA and strength were readily accepted in these Chinese urban and rural populations. The PAQ on physical activity in the past year produced some plausible population averages, but individual responses suggested recall challenges. If data about specific activities are required, future studies should explore use of standardized survey questions concerning such fewer specific activities or instruments examining shorter time periods such as one, three, or seven day recalls.

Epidemiological Studies of Low-Dose Ionizing Radiation and Cancer: Summary Bias Assessment and Meta-Analysis.

BACKGROUND: Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases. METHODS: Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006-2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia. RESULTS: Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P = .001), also after exclusion of 5 positive studies with potential positive bias (P = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers. CONCLUSIONS: Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.

Outcome Assessment in Epidemiological Studies of Low-Dose Radiation Exposure and Cancer Risks: Sources, Level of Ascertainment, and Misclassification.

BACKGROUND: Outcome assessment problems and errors that could lead to biased risk estimates in low-dose radiation epidemiological studies of cancer risks have not been systematically evaluated. METHODS: Incidence or mortality risks for all cancers or all solid cancers combined and for leukemia were examined in 26 studies published in 2006-2017 involving low-dose (mean dose ≤100 mGy) radiation from environmental, medical, or occupational sources. We evaluated the impact of loss to follow-up, under- or overascertainment, outcome misclassification, and changing classifications occurring similarly or differentially across radiation dose levels. RESULTS: Loss to follow-up was not reported in 62% of studies, but when reported it was generally small. Only one study critically evaluated the completeness of the sources of vital status. Underascertainment of cancers ("false negatives") was a potential shortcoming for cohorts that could not be linked with high-quality population-based registries, particularly during early years of exposure in five studies, in two lacking complete residential history, and in one with substantial emigration. False positives may have occurred as a result of cancer ascertainment from self- or next-of-kin report in three studies or from enhanced medical surveillance of exposed patients that could lead to detection bias (eg, reporting precancer lesions as physician-diagnosed cancer) in one study. Most pediatric but few adult leukemia studies used expert hematopathology review or current classifications. Only a few studies recoded solid cancers to the latest International Classification of Diseases or International Classification of Diseases for Oncology codes. These outcome assessment shortcomings were generally nondifferential in relation to radiation exposure level except possibly in four studies. CONCLUSION: The majority of studies lacked information to enable comprehensive evaluation of all major sources of outcome assessment errors, although reported data suggested that the outcome assessment limitations generally had little effect on risk or biased estimates towards the null except possibly in four studies.

Association of Chemotherapy for Solid Tumors With Development of Therapy-Related Myelodysplastic Syndrome or Acute Myeloid Leukemia in the Modern Era.

Importance: Therapy-related myelodysplastic syndrome or acute myeloid leukemia (tMDS/AML) is a rare, usually fatal complication of chemotherapy, including certain alkylating agents, topoisomerase II inhibitors, and platinum compounds. With the introduction of new chemotherapeutic agents, expanded indications for established agents, and increased neoadjuvant and adjuvant chemotherapy, tMDS/AML risks in the modern age are poorly understood. Objectives: To quantify tMDS/AML risk after chemotherapy for solid cancer among United States adults since 2000 and correlate tMDS/AML risk patterns with chemotherapy treatment practices. Design, Setting, and Participants: A population-based cohort study was conducted using cancer registries from the Surveillance, Epidemiology, and End Results (SEER) Program and Medicare claims. Risk analyses included 1619 tMDS/AML cases among 700 612 adults (age, 20-84 years) who were diagnosed with first primary solid cancer during 2000 to 2013 (followed up through 2014), received initial chemotherapy, and survived 1 year or longer, as reported to SEER. Descriptive analyses were conducted of SEER records linked with Medicare claims for chemotherapy in 165 820 older adults (age, 66-84 years) receiving initial chemotherapy for a first primary solid cancer in 2000-2013. Data analysis was conducted from October 2017 to April 2018. Exposures: Receipt of initial chemotherapy for solid cancer. Main Outcomes and Measures: Second primary tMDS/AML. Results: Based on 1619 tMDS/AML cases in the SEER database (mean [SD] age, 64.3 [12.2] years; 1148 [70.9%] female), tMDS/AML risks were statistically significantly elevated after chemotherapy for 22 of 23 solid cancers (all except colon). Relative risks ranged from 1.5 to greater than 10 and excess absolute risks from 1.4 to greater than 15 cases per 10 000 person-years compared with the general population. Overall survival following tMDS/AML diagnosis was poor (1270 of 1619 patients [78.4%] died; median overall survival, 7 months). For patients treated with chemotherapy at the present time, approximately three-quarters of tMDS/AML cases expected to occur within the next 5 years will be attributable to chemotherapy. In the SEER-Medicare database, use of known leukemogenic agents, particularly platinum compounds, in initial chemotherapy increased substantially since 2000, most notably for gastrointestinal tract cancers (esophagus, stomach, colon, and rectum; 10% in 2000-2001 to 81% during 2012-2013). Conclusions and Relevance: Large-scale, United States population-based data demonstrate excess tMDS/AML risks following chemotherapy for nearly all solid tumor types, consistent with expanded use of known leukemogenic agents in the 21st century. Continued efforts to reduce treatment-related adverse events, particularly for solid cancer patients with favorable prognosis, are needed.

Improving Assessment of Lifetime Solar Ultraviolet Radiation Exposure in Epidemiologic Studies: Comparison of Ultraviolet Exposure Assessment Methods in a Nationwide U.S. Occupational Cohort.

Solar ultraviolet radiation is the primary risk factor for skin cancers and sun-related eye disorders. Estimates of individual ambient ultraviolet irradiance derived from ground-based solar measurements and from satellite measurements have rarely been compared. Using self-reported residential history from 67 189 persons in a nationwide occupational US radiologic technologists' cohort, we estimated ambient solar irradiance using data from ground-based meters and noontime satellite measurements. The mean distance moved from city of longest residence in childhood increased from 137.6 km at ages 13-19 to 870.3 km at ages ≥65, with corresponding increases in absolute latitude difference moved. At ages 20/40/60/80, the Pearson/Spearman correlation coefficients of ground-based and satellite-derived potential solar ultraviolet exposure, using irradiance and cumulative radiant exposure metrics, were high (=0.87-0.92). There was also moderate correlation (Pearson/Spearman correlation coefficients = 0.51-0.60) between irradiance at birth and at last-known address, for ground-based and satellite data. Satellite-based lifetime estimates of ultraviolet radiation were generally 14-15% lower than ground-based estimates, albeit with substantial uncertainties, possibly because ground-based estimates incorporate fluctuations in cloud and ozone, which are incompletely incorporated in the single noontime satellite-overpass ultraviolet value. If confirmed elsewhere, the findings suggest that ground-based estimates may improve exposure assessment accuracy and potentially provide new insights into ultraviolet radiation-disease relationships in epidemiologic studies.

Assessment of thyroid cancer risk associated with radiation dose from personal diagnostic examinations in a cohort study of US radiologic technologists, followed 1983-2014.

OBJECTIVE: To assess whether personal medical diagnostic procedures over life, but particularly those associated with exposure in adulthood, were associated with increased thyroid cancer risk. DESIGN: Participants from the US Radiologic Technologists Study, a large, prospective cohort, were followed from the date of first mailed questionnaire survey completed during 1983-1989 to the earliest date of self-reported diagnosis of thyroid cancer or of any other cancer than non-melanoma skin cancer (NMSC) in any of three subsequent questionnaires up to the last in 2012-2014. SETTING: US nationwide, occupational cohort. PARTICIPANTS: US radiologic technologists with exclusion of: those who reported a previous cancer apart from NMSC on the first questionnaire; those who reported a cancer with an unknown date of diagnosis on any of the questionnaires; and those who did not respond to both the first questionnaire and at least one subsequent questionnaire. PRIMARY OUTCOME MEASURE: We used Cox proportional hazards models with age as timescale to compute HRs and 95% CI for thyroid cancer in relation to cumulative 5-year lagged diagnostic thyroid dose. RESULTS: There were 414 self-reported thyroid cancers (n=275 papillary) in a cohort of 76 415 persons. Cumulative thyroid dose was non-significantly positively associated with total (excess relative risk/Gy=2.29 (95% CI -0.91 to 7.01, p=0.19)) and papillary thyroid cancer (excess relative risk/Gy=4.15 (95% CI -0.39, 11.27, p=0.08)) risk. These associations were not modified by age at, or time since, exposure and were independent of occupational exposure. CONCLUSION: Our study provides weak evidence that thyroid dose from diagnostic radiation procedures over the whole of life, in particular associated with exposure in adulthood, influences adult thyroid cancer risk.

Hyperthyroidism, Hypothyroidism, and Cause-Specific Mortality in a Large Cohort of Women.

BACKGROUND: The prevalence of hyperthyroidism and hypothyroidism is 0.5-4% in iodine-replete communities, but it is 5-10 times higher in women than in men. Those conditions are associated with a broad range of metabolic disorders and cardiovascular diseases. Biological evidence of a role of thyroid hormones in carcinogenesis also exists. However, the association between thyroid dysfunction and cardiovascular disease or cancer mortality risk remains controversial. In a large cohort of women, the associations of hyperthyroidism and hypothyroidism with cause-specific mortality were evaluated after nearly 30 years of follow-up. METHODS: The prospective study included 75,076 women aged 20-89 years who were certified as radiologic technologists in the United States in 1926-1982, completed baseline questionnaires in 1983-1998 from which medical history was ascertained, and reported no malignant disease or benign thyroid disease except thyroid dysfunction. A passive follow-up of this cohort was performed through the Social Security Administration database and the National Death Index-Plus. Cause-specific mortality risks were compared according to self-reported thyroid status, with proportional hazards models adjusted for baseline year and age, race/ethnicity, body mass index, family history of breast cancer, and life-style and reproductive factors. RESULTS: During a median follow-up of 28 years, 2609 cancer, 1789 cardiovascular or cerebrovascular, and 2442 other non-cancer deaths were recorded. Women with hyperthyroidism had an elevated risk of breast cancer mortality after 60 years of age (hazard ratio [HR] = 2.04 [confidence interval (CI) 1.16-3.60], 13 cases in hyperthyroid women) compared to women without thyroid disease. Hypothyroid women had increased mortality risks for diabetes mellitus (HR = 1.58 [CI 1.03-2.41], 27 cases in hypothyroid women), cardiovascular disease (HR = 1.20 [CI 1.01-1.42], 179 cases), and cerebrovascular disease (HR = 1.45 [CI 1.01-2.08], 35 cases, when restricting the follow-up to ≥10 years after baseline). Other causes of death were not associated with hyperthyroidism or hypothyroidism, though there was a suggestion of an elevated risk of ovarian cancer mortality in hyperthyroid women based on very few cases. CONCLUSION: The excess mortality risks observed in a large, prospective 30-year follow-up of patients with thyroid dysfunction require confirmation, and, if replicated, further investigation will be needed because of the clinical implications.

Long-term Mortality in 43 763 U.S. Radiologists Compared with 64 990 U.S. Psychiatrists.

Purpose To compare mortality rates from all causes, specific causes, total cancers, and specific cancers to assess whether differences between radiologists and psychiatrists are consistent with known risks of radiation exposure and the changes in radiation exposure to radiologists over time. Materials and Methods The authors used the American Medical Association Physician Masterfile to construct a cohort of 43 763 radiologists (20% women) and 64 990 psychiatrists (27% women) (comparison group) who graduated from medical school in 1916-2006. Vital status was obtained from record linkages with the Social Security Administration and commercial databases, and cause of death was obtained from the National Death Index. Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for all causes and specific causes of death. Results During the follow-up period (1979-2008), 4260 male radiologists and 7815 male psychiatrists died. The male radiologists had lower death rates (all causes) compared with the psychiatrists (RR = 0.94; 95% CI: 0.90, 0.97), similar cancer death rates overall (RR = 1.00; 95% CI: 0.93, 1.07), but increased acute myeloid leukemia and/or myelodysplastic syndrome death rates (RR = 1.62; 95% CI: 1.05, 2.50); these rates were driven by those who graduated before 1940 (RR = 4.68; 95% CI: 0.91, 24.18). In these earliest workers (before 1940) there were also increased death rates from melanoma (RR = 8.75; 95% CI: 1.89, 40.53), non-Hodgkin lymphoma (NHL) (RR = 2.69; 95% CI: 1.33, 5.45), and cerebrovascular disease (RR = 1.49; 95% CI: 1.11, 2.01). The 208 deaths in female radiologists precluded detailed investigation, and the number of female radiologists who graduated before 1940 was very small (n = 47). Conclusion The excess risk of acute myeloid leukemia and/or myelodysplastic syndrome mortality in radiologists who graduated before 1940 is likely due to occupational radiation exposure. The melanoma, NHL, and cerebrovascular disease mortality risks are possibly due to radiation. The authors found no evidence of excess mortality in radiologists who graduated more recently, possibly because of increased radiation protection and/or lifestyle changes. © RSNA, 2016 Online supplemental material is available for this article.

Retrospective benzene exposure assessment for a multi-center case-cohort study of benzene-exposed workers in China.

Quality of exposure assessment has been shown to be related to the ability to detect risk of lymphohematopoietic disorders in epidemiological investigations of benzene, especially at low levels of exposure. We set out to build a statistical model for reconstructing exposure levels for 2898 subjects from 501 factories that were part of a nested case-cohort study within the NCI-CAPM cohort of more than 110,000 workers. We used a hierarchical model to allow for clustering of measurements by factory, workshop, job, and date. To calibrate the model we used historical routine monitoring data. Measurements below the limit of detection were accommodated by constructing a censored data likelihood. Potential non-linear and industry-specific time-trends and predictor effects were incorporated using regression splines and random effects. A partial validation of predicted exposures in 2004/2005 was performed through comparison with full-shift measurements from an exposure survey in facilities that were still open. Median cumulative exposure to benzene at age 50 for subjects that ever held an exposed job (n=1175) was 509 mg/m(3) years. Direct comparison of model estimates with measured full-shift personal exposure in the 2004/2005 survey showed moderate correlation and a potential downward bias at low (<1 mg/m(3)) exposure estimates. The modeling framework enabled us to deal with the data complexities generally found in studies using historical exposure data in a comprehensive way and we therefore expect to be able to investigate effects at relatively low exposure levels.

Nuclear medicine practices in the 1950s through the mid-1970s and occupational radiation doses to technologists from diagnostic radioisotope procedures.

Data on occupational radiation exposure from nuclear medicine procedures for the time period of the 1950s through the 1970s is important for retrospective health risk studies of medical personnel who conducted those activities. However, limited information is available on occupational exposure received by physicians and technologists who performed nuclear medicine procedures during those years. To better understand and characterize historical radiation exposures to technologists, the authors collected information on nuclear medicine practices in the 1950s, 1960s, and 1970s. To collect historical data needed to reconstruct doses to technologists, a focus group interview was held with experts who began using radioisotopes in medicine in the 1950s and the 1960s. Typical protocols and descriptions of clinical practices of diagnostic radioisotope procedures were defined by the focus group and were used to estimate occupational doses received by personnel, per nuclear medicine procedure, conducted in the 1950s to 1960s using radiopharmaceuticals available at that time. The radionuclide activities in the organs of the reference patient were calculated using the biokinetic models described in ICRP Publication 53. Air kerma rates as a function of distance from a reference patient were calculated by Monte Carlo radiation transport calculations using a hybrid computational phantom. Estimates of occupational doses to nuclear medicine technologists per procedure were found to vary from less than 0.01 µSv (thyroid scan with 1.85 MBq of administered I-iodide) to 0.4 µSv (brain scan with 26 MBq of Hg-chlormerodin). Occupational doses for the same diagnostic procedures starting in the mid-1960s but using Tc were also estimated. The doses estimated in this study show that the introduction of Tc resulted in an increase in occupational doses per procedure.

Association of chromosome translocation rate with low dose occupational radiation exposures in U.S. radiologic technologists.

Chromosome translocations are a well-recognized biological marker of radiation exposure and cancer risk. However, there is uncertainty about the lowest dose at which excess translocations can be detected, and whether there is temporal decay of induced translocations in radiation-exposed populations. Dosimetric uncertainties can substantially alter the shape of dose-response relationships; although regression-calibration methods have been used in some datasets, these have not been applied in radio-occupational studies, where there are also complex patterns of shared and unshared errors that these methods do not account for. In this article we evaluated the relationship between estimated occupational ionizing radiation doses and chromosome translocation rates using fluorescent in situ hybridization in 238 U.S. radiologic technologists selected from a large cohort. Estimated cumulative red bone marrow doses (mean 29.3 mGy, range 0-135.7 mGy) were based on available badge-dose measurement data and on questionnaire-reported work history factors. Dosimetric assessment uncertainties were evaluated using regression calibration, Bayesian and Monte Carlo maximum likelihood methods, taking account of shared and unshared error and adjusted for overdispersion. There was a significant dose response for estimated occupational radiation exposure, adjusted for questionnaire-based personal diagnostic radiation, age, sex and study group (5.7 translocations per 100 whole genome cell equivalents per Gy, 95% CI 0.2, 11.3, P = 0.0440). A significant increasing trend with dose continued to be observed for individuals with estimated doses <100 mGy. For combined estimated occupational and personal-diagnostic-medical radiation exposures, there was a borderline-significant modifying effect of age (P = 0.0704), but little evidence (P > 0.5) of temporal decay of induced translocations. The three methods of analysis to adjust for dose uncertainty gave similar results. In summary, chromosome translocation dose-response slopes were detectable down to <100 mGy and were compatible with those observed in other radiation-exposed populations. However, there are substantial uncertainties in both occupational and other (personal-diagnostic-medical) doses that may be imperfectly taken into account in our analysis.

Body mass index and risk of death in Asian Americans.

OBJECTIVES: We investigated the association between body mass index (BMI) and mortality among Asian Americans. METHODS: We pooled data from prospective cohort studies with 20 672 Asian American adults with no baseline cancer or heart disease history. We estimated hazard ratios and 95% confidence intervals (CIs) with Cox proportional hazards models. RESULTS: A high, but not low, BMI was associated with increased risk of total mortality among individuals aged 35 to 69 years. The BMI was not related to total mortality among individuals aged 70 years and older. With a BMI 22.5 to < 25 as the reference category among never-smokers aged 35 to 69 years, the hazard ratios for total mortality were 0.83 (95% CI = 0.47, 1.47) for BMI 15 to < 18.5; 0.91 (95% CI = 0.62, 1.32) for BMI 18.5 to < 20; 1.08 (95% CI = 0.86, 1.36) for BMI 20 to < 22.5; 1.14 (95% CI = 0.90, 1.44) for BMI 25 to < 27.5; 1.13 (95% CI = 0.79, 1.62) for BMI 27.5 to < 30; 1.82 (95% CI = 1.25, 2.64) for BMI 30 to < 35; and 2.09 (95% CI = 1.06, 4.11) for BMI 35 to 50. Higher BMI was also related to increased cardiovascular disease and cancer mortality. CONCLUSIONS: High BMI is associated with increased mortality risk among Asian Americans.

Guidelines for exposure assessment in health risk studies following a nuclear reactor accident.

BACKGROUND: Worldwide concerns regarding health effects after the Chernobyl and Fukushima nuclear power plant accidents indicate a clear need to identify short- and long-term health impacts that might result from accidents in the future. Fundamental to addressing this problem are reliable and accurate radiation dose estimates for the affected populations. The available guidance for activities following nuclear accidents is limited with regard to strategies for dose assessment in health risk studies. OBJECTIVES: Here we propose a comprehensive systematic approach to estimating radiation doses for the evaluation of health risks resulting from a nuclear power plant accident, reflected in a set of seven guidelines. DISCUSSION: Four major nuclear reactor accidents have occurred during the history of nuclear power production. The circumstances leading to these accidents were varied, as were the magnitude of the releases of radioactive materials, the pathways by which persons were exposed, the data collected afterward, and the lifestyle factors and dietary consumption that played an important role in the associated radiation exposure of the affected populations. Accidents involving nuclear reactors may occur in the future under a variety of conditions. The guidelines we recommend here are intended to facilitate obtaining reliable dose estimations for a range of different exposure conditions. We recognize that full implementation of the proposed approach may not always be feasible because of other priorities during the nuclear accident emergency and because of limited resources in manpower and equipment. CONCLUSIONS: The proposed approach can serve as a basis to optimize the value of radiation dose reconstruction following a nuclear reactor accident.

Comparison of occupational exposure assessment methods in a case-control study of lead, genetic susceptibility and risk of adult brain tumours.

OBJECTIVES: There is great interest in evaluating gene-environment interactions with chemical exposures, but exposure assessment poses a unique challenge in case-control studies. Expert assessment of detailed work history data is usually considered the best approach, but it is a laborious and time-consuming process. We set out to determine if a less intensive method of exposure assessment (a job exposure matrix (JEM)) would produce similar results to a previous analysis that found evidence of effect modification of the association between expert-assessed lead exposure and risk of brain tumours by a single nucleotide polymorphism in the ALAD gene (rs1800435). METHODS: We used data from a study of 355 patients with glioma, 151 patients with meningioma and 505 controls. Logistic regression models were used to examine associations between brain tumour risk and lead exposure and effect modification by genotype. We evaluated Cohen's κ, sensitivity and specificity for the JEM compared to the expert-assessed exposure metrics. RESULTS: Although effect estimates were imprecise and driven by a small number of cases, we found evidence of effect modification between lead exposure and ALAD genotype when using expert- but not JEM-derived lead exposure estimates. κ Values indicated only modest agreement (<0.5) for the exposure metrics, with the JEM indicating high specificity (∼0.9) but poor sensitivity (∼0.5). Disagreement between the two methods was generally due to having additional information in the detailed work history. CONCLUSION: These results provide preliminary evidence suggesting that high quality exposure data are likely to improve the ability to detect genetic effect modification.

Assessment of lifetime cumulative sun exposure using a self-administered questionnaire: reliability of two approaches.

Few studies have evaluated the reliability of lifetime sun exposure estimated from inquiring about the number of hours people spent outdoors in a given period on a typical weekday or weekend day (the time-based approach). Some investigations have suggested that women have a particularly difficult task in estimating time outdoors in adulthood due to their family and occupational roles. We hypothesized that people might gain additional memory cues and estimate lifetime hours spent outdoors more reliably if asked about time spent outdoors according to specific activities (an activity-based approach). Using self-administered, mailed questionnaires, test-retest responses to time-based and to activity-based approaches were evaluated in 124 volunteer radiologic technologist participants from the United States: 64 females and 60 males 48 to 80 years of age. Intraclass correlation coefficients (ICC) were used to evaluate the test-retest reliability of average number of hours spent outdoors in the summer estimated for each approach. We tested the differences between the two ICCs, corresponding to each approach, using a t test with the variance of the difference estimated by the jackknife method. During childhood and adolescence, the two approaches gave similar ICCs for average numbers of hours spent outdoors in the summer. By contrast, compared with the time-based approach, the activity-based approach showed significantly higher ICCs during adult ages (0.69 versus 0.43, P = 0.003) and over the lifetime (0.69 versus 0.52, P = 0.05); the higher ICCs for the activity-based questionnaire were primarily derived from the results for females. Research is needed to further improve the activity-based questionnaire approach for long-term sun exposure assessment.

Simplified categorization of outdoor activities for male and female U.S. indoor workers-a feasibility study to improve assessment of ultraviolet radiation exposures in epidemiologic study questionnaires.

Skin cancer studies depend on questionnaires to estimate exposure to ultraviolet light and subsequent risk but are limited by recall bias. We investigate the feasibility of developing a short checklist of categories comprising outdoor activities that can improve sun exposure questionnaires for use in epidemiologic studies. We recruited 124 working and retired U.S. radiologic technologists (52% women). Each subject was instructed to complete a daily activity diary, listing main indoor and outdoor activities between 9:00 A.M. and 5:00 P.M. during a 7 day period. A total of 4,697 entries were associated with 1408 h (21.1%) of the total 6,944 h spent outdoors. We were able to classify the activities into seven main activity categories: driving, yard work, home-maintenance, walking or performing errands, water activities, other recreational or sports activities and leisure activities or relaxing outside. These activities accounted for more than 94% of time spent outdoors both for working and retired men and women. Our data document the feasibility and guidance for developing a short checklist of outdoor activities for use in epidemiologic questionnaires for estimating sunlight exposures of working and retired indoor workers.

Measures of cumulative exposure from a standardized sun exposure history questionnaire: a comparison with histologic assessment of solar skin damage.

Ultraviolet radiation exposure is the dominant environmental determinant of all major forms of skin cancer; however, the nature of the association is incompletely understood. Existing instruments to capture sun exposure history tend to yield reproducible results, but the validity of these responses is unknown. To address this question, the authors examined the relation between responses to a standardized sun exposure instrument and histologic evidence of actinic damage in a population-based study of keratinocyte cancers from New Hampshire diagnosed from July 1, 1997, through March 31, 2000. A single study dermatopathologist histologically reviewed the adjacent skin of 925 skin cancer biopsies for the presence of solar keratoses and the extent of solar elastosis. The authors compared these measures with responses to a personal interview on history of sunburns, sunbathing, and time spent outdoors. Focusing on site-specific exposure, they found variables that estimated cumulative exposure related to histologic evidence of actinic damage. In contrast, measures of acute/intermittent exposure were generally unrelated to solar damage histologically. Findings suggest that cumulative, but not intermittent, measures of sun exposure derived from a personal interview appear to reflect a person's exposure history based on histologic evidence.

Detailed exposure assessment for a molecular epidemiology study of benzene in two shoe factories in China.

OBJECTIVES: We carried out a detailed exposure assessment of benzene and toluene in two shoe factories in Tianjin, China. Our goal was to identify workers with a broad range of benzene exposures, for an epidemiologic study relating exposure to early biologic effects. METHODS: A comprehensive exposure survey program was initiated. Over a period of 16 months, 2783 personal solvent exposure samples were collected in two workplaces from 250 workers. Mixed-effects models were used to identify factors affecting exposure. Principal component analyses (PCA) and subsequent regression analyses on the scores of the identified principal components were used to relate potential co-exposures to various exposure sources present in the workplace. RESULTS: The mean benzene exposure level was 21.86 p.p.m. (10th-90th percentiles 5.23-50.63 p.p.m.) in the smaller shoe factory (factory A) and 3.46 p.p.m. (10th-90th percentiles 0.20-7.00 p.p.m.) in the larger shoe factory (factory B). Within-factory exposure levels differed among job titles and were higher for subjects directly involved in handling glues. In contrast, mean toluene levels were relatively similar in the two factories (factory A, 9.52 p.p.m.; factory B, 15.88 p.p.m.). A seasonal trend was identified for both benzene and toluene in factory B. This could be explained in part by changes in air movement and ventilation patterns occurring during the year. A seasonal trend was not present in the smaller shoe factory, where general ventilation was absent. Supplemental analysis showed that exposure levels to other hydrocarbons were low (< or =5 p.p.m.), less than 5% of their respective ACGIH threshold limit values, and generally comparable in the two factories. PCA showed that co-exposures in factory B could largely be explained by glue sources that were used in distinct areas in the workplace. CONCLUSIONS: We demonstrated the occurrence of a broad range of benzene exposure levels in two shoe manufacturing factories in Tianjin, China. Benzene and toluene exposures were determined in part by the degree of contact with glues, the benzene and toluene content of each glue, air movement and ventilation patterns. The availability of long-term monthly personal monitoring data provides an excellent opportunity to estimate individual exposures at different times during the 1 yr period of observation.

Randomized trial of financial incentives and delivery methods for improving response to a mailed questionnaire.

In a follow-up study, only 64% of 126,628 US radiologic technologists completed a questionnaire during 1994-1997 after two mailings. The authors conducted a randomized trial of financial incentives and delivery methods to identify the least costly approach for increasing overall participation. They randomly selected nine samples of 300 nonresponders each to receive combinations of no, 1.00 US dollar, 2.00 US dollars, and 5.00 US dollars cash or check incentives delivered by first-class mail or Federal Express. Federal Express delivery did not achieve greater participation than first-class mail (23.2% vs. 23.7%). In analyses pooled across delivery methods, the response was significantly greater for the 2.00 US dollar bill (28.9%, 95% confidence interval (CI): 25.2, 32.7; p < 0.0001), 5.00 US dollars check (27.5%, 95% CI: 22.5, 33.0; p = 0.0001), 1.00 US dollar bill (24.6%, 95% CI: 21.2, 28.3; p = 0.0007), and 2.00 US dollars check (21.8%, 95% CI: 18.5, 25.3; p = 0.02) compared with no incentive (16.6%, 95% CI: 13.7, 19.9). The response increased significantly with increasing incentive amounts from 0.00 to 2.00 US dollars cash (p trend < 0.0001). The 2.00 US dollar bill achieved a 30% greater response than did a 2.00 US dollars check (p = 0.005). For incentives sent by first-class mail, the 5.00 US dollars check yielded 30% greater participation than did the 2.00 US dollars check (p = 0.07). A 1.00 US dollar bill, chosen instead of the 2.00 US dollars bill because of substantially lower overall cost and sent by first-class mail to the remaining 42,717 nonresponders, increased response from 64% to 72%.

Sociodemographic indicators and risk of brain tumours.

BACKGROUND: To better understand patterns of occurrence or diagnosis of brain tumours in different segments of the population, we evaluated associations between sociodemographic variables and the relative incidence of brain tumours as part of a multi-faceted case-control study. METHODS: The study was conducted at hospitals in three US cities between 1994 and 1998. In all, 489 glioma cases (354 high-grade, 135 low-grade), 197 meningioma cases, 96 acoustic neuroma cases, and 799 controls admitted to the same hospitals for any of a variety of non-neoplastic diseases or conditions were enrolled and interviewed. Logistic regression was used to estimate odds ratios (OR), calculate 95% CI, and test for trends. RESULTS: The OR showed significant positive associations with household income for low-grade glioma, meningioma, and acoustic neuroma, but not for high-grade glioma. Positive associations were observed with level of education for low-grade glioma and acoustic neuroma, but not for high-grade glioma or meningioma. Jewish religion was associated with a significantly elevated risk for meningioma (OR = 4.3; 95% CI: 2.0-9.0). Being single at the time of tumour diagnosis or enrolment was associated with significantly reduced risks for meningioma (OR = 0.4; 95% CI: 0.3-0.6) and low- or high-grade glioma (OR = 0.6; 95% CI: 0.5-0.8), but not for acoustic neuroma. CONCLUSIONS: Associations with sociodemographic variables varied considerably among the different subtypes of brain tumour, including between low-grade and high-grade glioma. The general pattern was for associations with indicators of affluence and education to be stronger for tumours that tend to grow more slowly and have less catastrophic effects, although the evidence was mixed for meningioma. We cannot isolate the specific factors underlying the observed associations, but intrapopulation differences in the completeness or timing of diagnosis may have played a role. There is less opportunity for such influences to operate for the rapidly progressing, high-grade gliomas than for more slowly growing tumours.