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1.  Acetylcholinesterase Activity and Neurodevelopment in Boys and Girls 
Pediatrics  2013;132(6):e1649-e1658.
Organophosphate exposures can affect children’s neurodevelopment, possibly due to neurotoxicity induced by acetylcholinesterase (AChE) inhibition, and may affect boys more than girls. We tested the hypothesis that lower AChE activity is associated with lower neurobehavioral development among children living in Ecuadorian floricultural communities.
In 2008, we examined 307 children (age: 4–9 years; 52% male) and quantified AChE activity and neurodevelopment in 5 domains: attention/executive functioning, language, memory/learning, visuospatial processing, and sensorimotor (NEPSY-II test). Associations were adjusted for demographic and socioeconomic characteristics and height-for-age, flower worker cohabitation, and hemoglobin concentration.
Mean ± standard deviation AChE activity was 3.14 ± 0.49 U/mL (similar for both genders). The range of scores among neurodevelopment subtests was 5.9 to 10.7 U (standard deviation: 2.6–4.9 U). Girls had a greater mean attention/executive functioning domain score than boys. In boys only, there were increased odds ratios of low (<9th percentile) neurodevelopment among those in the lowest tertile versus the highest tertile of AChE activity (odds ratios: total neurodevelopment: 5.14 [95% confidence interval (CI): 0.84 to 31.48]; attention/executive functioning domain: 4.55 [95% CI: 1.19 to 17.38], memory/learning domain: 6.03 [95% CI: 1.17 to 31.05]) after adjustment for socioeconomic and demographic factors, height-for-age, and hemoglobin. Within these domains, attention, inhibition and long-term memory subtests were most affected.
Low AChE activity was associated with deficits in neurodevelopment, particularly in attention, inhibition, and memory in boys but not in girls. These critical cognitive skills affect learning and academic performance. Added precautions regarding secondary occupational pesticide exposure would be prudent.
PMCID: PMC3838526  PMID: 24249815
acetylcholinesterase; AChE; ADD; ADHD; agriculture; agricultural communities; attention; boys; children; Ecuador; floriculture; flower; girls; growth; inhibition; inhibitory control; memory; neurobehavioral development; neurodevelopment; plantation; pesticide
2.  Quantifying Lead-Time Bias in Risk-Factor Studies of Cancer through Simulation 
Annals of epidemiology  2013;23(11):10.1016/j.annepidem.2013.07.021.
Lead-time is inherent in early detection and creates bias in observational studies of screening efficacy, but its potential to bias effect estimates in risk-factor studies is not always recognized. We describe a form of this bias that conventional analyses cannot address and develop a model to quantify it.
Surveillance Epidemiology and End Results (SEER) data form the basis for estimates of age-specific preclinical incidence and log-normal distributions describe the preclinical duration distribution. Simulations assume a joint null hypothesis of no effect of either the risk factor or screening on the preclinical incidence of cancer, and then quantify the bias as the risk-factor odds ratio (OR) from this null study. This bias can be used as a factor to adjust observed OR in the actual study.
Results showed that for this particular study design, as average preclinical duration increased, the bias in the total-physical-activity OR monotonically increased from 1% to 22% above the null, but the smoking OR monotonically decreased from 1% above the null to 5% below the null.
The finding of nontrivial bias in fixed risk-factor effect estimates demonstrates the importance of quantitatively evaluating it in susceptible studies.
PMCID: PMC3839248  PMID: 23988688
methodological study; case-control study; early diagnosis of cancer; cancer screening; mathematical model; bias
3.  A Prospective Study of Medical Diagnostic Radiography and Risk of Thyroid Cancer 
American Journal of Epidemiology  2013;177(8):800-809.
Although diagnostic x-ray procedures provide important medical benefits, cancer risks associated with their exposure are also possible, but not well characterized. The US Radiologic Technologists Study (1983–2006) is a nationwide, prospective cohort study with extensive questionnaire data on history of personal diagnostic imaging procedures collected prior to cancer diagnosis. We used Cox proportional hazard regressions to estimate thyroid cancer risks related to the number and type of selected procedures. We assessed potential modifying effects of age and calendar year of the first x-ray procedure in each category of procedures. Incident thyroid cancers (n = 251) were diagnosed among 75,494 technologists (1.3 million person-years; mean follow-up = 17 years). Overall, there was no clear evidence of thyroid cancer risk associated with diagnostic x-rays except for dental x-rays. We observed a 13% increase in thyroid cancer risk for every 10 reported dental radiographs (hazard ratio = 1.13, 95% confidence interval: 1.01, 1.26), which was driven by dental x-rays first received before 1970, but we found no evidence that the relationship between dental x-rays and thyroid cancer was associated with childhood or adolescent exposures as would have been anticipated. The lack of association of thyroid cancer with x-ray procedures that expose the thyroid to higher radiation doses than do dental x-rays underscores the need to conduct a detailed radiation exposure assessment to enable quantitative evaluation of risk.
PMCID: PMC3668423  PMID: 23529772
radiation; radiography; thyroid gland; thyroid neoplasms; x-rays
4.  Nucleotide excision repair polymorphisms may modify ionizing radiation-related breast cancer risk in US radiologic technologists 
Exposure to ionizing radiation has been consistently associated with increased risk of female breast cancer. Although the majority of DNA damage caused by ionizing radiation is corrected by the base-excision repair pathway, certain types of multiple-base damage can only be repaired through the nucleotide excision repair pathway. In a nested case–control study of breast cancer in US radiologic technologists exposed to low levels of ionizing radiation (858 cases, 1,083 controls), we examined whether risk of breast cancer conferred by radiation was modified by nucleotide excision gene polymorphisms ERCC2 (XPD) rs13181, ERCC4 (XPF) rs1800067 and rs1800124, ERCC5 (XPG) rs1047769 and rs17655; and ERCC6 rs2228526. Of the 6 ERCC variants examined, only ERCC5 rs17655 showed a borderline main effect association with breast cancer risk (ORGC = 1.1, ORCC = 1.3; p-trend = 0.08), with some indication that individuals carrying the C allele variant were more susceptible to the effects of occupational radiation (EOR/GyGG = 1.0, 95% CI = <0, 6.0; EOR/GyGC/CC = 5.9, 95% CI = 0.9, 14.4; phet = 0.10). ERCC2 rs13181, although not associated with breast cancer risk overall, statistically significantly modified the effect of occupational radiation dose on risk of breast cancer (EOR/GyAA = 9.1, 95% CI = 2.1–21.3; EOR/GyAC/CC = 0.6, 95% CI = <0, 4.6; phet = 0.01). These results suggest that common variants in nucleotide excision repair genes may modify the association between occupational radiation exposure and breast cancer risk.
PMCID: PMC3984912  PMID: 18767034
5.  Agreement Between Diary Records of Time Spent Outdoors and Personal Ultraviolet Radiation Dose Measurements 
Photochemistry and photobiology  2008;84(3):713-718.
Little is known about the validity of self-recorded sun exposure and time spent outdoors for epidemiological research. The aims of the current study were to assess how well participants’ self-recorded time outdoors compared to objective measurements of personal UVR doses. We enrolled 124 volunteers aged 40 and above who were identified from targeted subgroups of US radiologic technologists. Each volunteer was instructed to wear a polysulfone (PS) dosimeter to measure UVR on their left shoulder and to complete a daily activity diary, listing all activities undertaken in each 30 min interval between 9:00 A.M. and 5:00 P.M. during a 7 day period. In a linear regression model, self-recorded daily time spent outdoors was associated with an increase of 8.2% (95% CI: 7.3–9.2%) in the personal UVR exposure with every hour spent outdoors. The amount of self-recorded total daily time spent outdoors was better correlated with the personal daily UVR dose for activities conducted near noon time compared to activities conducted in the morning or late afternoon, and for activities often performed in the sun (e.g. gardening or recreation activities) compared to other outdoor activities (e.g. driving) in which the participant is usually shaded from the sun. Our results demonstrated a significant correlation between diary records of time spent outdoors with objective personal UVR dose measurements.
PMCID: PMC3966551  PMID: 18435619
6.  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 4697 entries were associated with 1408 h (21.1%) of the total 6944 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.
PMCID: PMC3956440  PMID: 18643910
7.  No Evidence for Differences in DNA Damage Assessed before and after a Cancer Diagnosis 
The overwhelming majority of studies that have found increased cancer risk associated with functional deficits in DNA repair used a case-control design, in which measurements were made after cancer diagnosis. However, there are concerns about whether the cancer itself or cancer treatment affected the conclusions (reverse causation bias). We assessed the effect of cancer diagnosis among 26 breast cancer controls who had blood collected during 2001 to 2003 and again in 2005 to 2006 after being diagnosed with cancer. Using the alkaline comet assay, we quantified DNA damage in untreated lymphoblastoid cell lines. Comet distributed moment, olive tail moment, percentage of DNA in tail, and comet tail length were summarized as the geometric mean of 100 cells. For comet distributed moment, olive tail moment, tail DNA, and tail length, the proportions of women with before diagnosis values higher than after diagnosis were 65%, 50%, 50%, and 46%, respectively. We found no significant differences in the before or after diagnosis mean comet values. Median cut-points were determined from the before diagnosis distribution, and we used conditional logistic regression to calculate odds ratios (OR) and upper 95% bounds of the confidence intervals. ORs ranged from 0.6 to 0.9 with upper confidence interval bounds of 1.9 and 2.6, meaning biased ORs above 2.6 are unlikely. We found no evidence that reverse causation bias is an important concern in case-control studies using the comet assay applied to cell lines collected after cancer diagnosis. More work is needed to characterize the effect of cancer diagnosis on other phenotypic assays.
PMCID: PMC3950930  PMID: 18398043
8.  Sunlight and Other Determinants of Circulating 25-Hydroxyvitamin D Levels in Black and White Participants in a Nationwide US Study 
American Journal of Epidemiology  2013;177(2):180-192.
Circulating 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, is associated with bone health and possibly cancers and other diseases; yet, the determinants of 25(OH)D status, particularly ultraviolet radiation (UVR) exposure, are poorly understood. Determinants of 25(OH)D were analyzed in a subcohort of 1,500 participants of the US Radiologic Technologists (USRT) Study that included whites (n = 842), blacks (n = 646), and people of other races/ethnicities (n = 12). Participants were recruited monthly (2008–2009) across age, sex, race, and ambient UVR level groups. Questionnaires addressing UVR and other exposures were generally completed within 9 days of blood collection. The relation between potential determinants and 25(OH)D levels was examined through regression analysis in a random two-thirds sample and validated in the remaining one third. In the regression model for the full study population, age, race, body mass index, some seasons, hours outdoors being physically active, and vitamin D supplement use were associated with 25(OH)D levels. In whites, generally, the same factors were explanatory. In blacks, only age and vitamin D supplement use predicted 25(OH)D concentrations. In the full population, determinants accounted for 25% of circulating 25(OH)D variability, with similar correlations for subgroups. Despite detailed data on UVR and other factors near the time of blood collection, the ability to explain 25(OH)D was modest.
PMCID: PMC3590034  PMID: 23292956
dietary supplements; 25-hydroxyvitamin D; race; seasons; sex; sunlight; ultraviolet rays; vitamin D
9.  Basal cell carcinoma and anthropometric factors in the U.S. Radiologic Technologists Cohort Study 
Basal cell carcinoma (BCC) is the most common cancer in Caucasian populations. Although several risk factors are well-established, including ultraviolet radiation (UVR) sensitivity and exposure, few studies have examined anthropometric measures and BCC. Using Cox proportional hazards regression analysis, we prospectively investigated the relationship between height, weight, and body mass index (BMI) and BCC in 58,213 Caucasian participants (11,631 men and 46,582 women) from the United States Radiological Technologists cohort. This analysis was limited to participants who were cancer-free at baseline. The baseline questionnaire provided self-reported anthropometric factors and the subsequent questionnaire collected skin cancer susceptibility factors, lifetime UVR exposure derived from residential and personal UVR exposure (time outdoors), and health outcomes. During 509,465 person-years of follow-up, we identified 2,291 BCC cases (486 men; 1,805 women). BCC risk increased with increasing height, and decreased with increasing weight and BMI in both sexes, even after adjusting for UVR susceptibility factors and exposures. For BMI categories: <25 (reference); 25–<30; 30–<35; and ≥ 35 kg/m2, multivariate hazard ratios (HR) in women were: 1.00; 0.74 (95% CI=0.66–0.83); 0.67 (0.56–0.81); and 0.57 (0.44–0.74) respectively, p-trend ≤0.0001. Risks were similar in men. The inverse association between BMI and BCC was unaffected by controlling for sun-related exposures. Nevertheless, it may at least partly reflect residual UVR confounding. Further research with more detailed sun exposure data, including clothing patterns, would help clarify the relationship between BMI and BCC.
PMCID: PMC3873091  PMID: 21989791
Basal cell carcinoma; weight; height; body mass index
10.  Work practices and childhood agricultural injury 
Injury Prevention  2007;13(6):409-415.
To evaluate whether children's agricultural work practices were associated with agricultural injury and to identify injury and work practice predictors.
Analyses were based on nested case–control data collected by the Regional Rural Injury Study‐II (RRIS‐II) surveillance study in 1999 and 2001 by computer‐assisted telephone interviews.
Cases (n  =  425) and controls (n  =  1886) were persons younger than 20 years of age from Midwestern agricultural households. Those reporting agricultural injuries became cases; controls (no injury) were selected using incidence density sampling.
Main outcome measures
Multivariate logistic regression was used to estimate the risks of injury associated with agricultural work, performing chores earlier than developmentally appropriate, hours worked per week, and number of chores performed.
Increased risks of injury were observed for children who performed chores 2–3 years younger than recommended, compared to being “age‐appropriate” (odds ratio (OR)  =  2.6, 95% confidence interval (CI)  =  1.4–4.5); performed any agricultural work (3.9 (2.6–5.6)); performed seven to ten chores per month compared to one chore (2.2 (1.3–3.5)); and worked 11–30 or 31–40 h per week compared to 1–10 h (1.6 (1.2–2.1) and 2.2 (1.3–3.7), respectively). Decreased risks of injury were observed for non‐working children compared to children performing what are commonly considered safe levels of agricultural work.
This study demonstrated elevated risks of agricultural injury among children who perform developmentally inappropriate chores. Results suggest that the efficacy of age restrictions for preventing the occurrence of childhood agricultural injuries warrants further evaluation.
PMCID: PMC2598295  PMID: 18056319
11.  Spatiotemporal and Spatial Threshold Models for Relating UV Exposures and Skin Cancer in the Central United States 
The exact mechanisms relating exposure to ultraviolet (UV) radiation and elevated risk of skin cancer remain the subject of debate. For example, there is disagreement on whether the main risk factor is duration of the exposure, its intensity, or some combination of both. There is also uncertainty regarding the form of the dose-response curve, with many authors believing only exposures exceeding a given (but unknown) threshold are important. In this paper we explore methods to estimate such thresholds using hierarchical spatial logistic models based on a sample of a cohort of x-ray technologists for whom we have self-reports of time spent in the sun and numbers of blistering sunburns in childhood. A preliminary goal is to explore the temporal pattern of UV exposure and its gradient. Changes here would imply that identical exposure self-reports from different calendar years may correspond to differing cancer risks.
PMCID: PMC2705173  PMID: 20161236
Conditionally autoregressive (CAR) model; Erythemal exposure; Hierarchical model; Non-melanoma skin cancer
12.  Livestock Density as Risk Factor for Livestock-associated Methicillin-Resistant Staphylococcus aureus, the Netherlands 
Emerging Infectious Diseases  2013;19(9):1551-1552.
PMCID: PMC3810905  PMID: 23968678
swine; livestock; cattle; geographic information systems; methicillin-resistant Staphylococcus aureus; MRSA; cluster analysis; bacteria; zoonoses; the Netherlands
13.  Estimates of restrictive ventilatory defect in the mining industry. Considerations for epidemiological investigations: a cross-sectional study 
BMJ Open  2013;3(7):e002561.
(1) To assess the impact of American Thoracic Society and European Respiratory Society (ATS/ERS) ‘acceptability’ and ‘usability’ criteria for spirometry on the estimates of restrictive ventilatory defect in a population of taconite miners. (2) To compare estimates of restrictive ventilatory defect with three different pulmonary function tests (spirometry, alveolar volume (VA) and diffusing capacity (DL,CO)). (3) To assess the role of population characteristics on these estimates.
Cross-sectional study.
Current and former workers in six current taconite mining operations of northeastern Minnesota were surveyed.
We attempted to enrol 3313 participants. Of these, 1353 responded while 1188 current and former workers fully participated in the survey and 1084 performed complete pulmonary function testing and were assessed.
Primary and secondary outcome measures
We applied ATS/ERS acceptability criteria for all tests and categorised participants into groups according to whether they fully met, partially met or did not meet acceptability criteria for spirometry. Obstruction and restriction were defined utilising the lower limit of normal for all tests. When using VA, restriction was identified after excluding obstruction.
Only 519 (47.9%) tests fully met ATS/ERS spirometry acceptability criteria. Within this group, 5% had obstruction and 6%, restriction on spirometry. In contrast, among all participants (N=1084), 16.8% had obstruction, while 4.5% had restriction. VA showed similar results in all groups after obstruction was excluded. Impaired gas transfer (reduced DL,CO) was identified in less than 50% of restriction identified by either spirometry or VA. Body mass index (BMI) was significantly related to spirometric restriction in all groups.
Population estimates of restriction using spirometry or VA varied by spirometric acceptability criteria. Other factors identified as important considerations in the estimation of restrictive ventilatory defect included increased BMI and gas transfer impairment in a relatively smaller proportion of those with spirometric restriction. These insights are important when interpreting population-based physiological data in occupational settings.
PMCID: PMC3717471  PMID: 23869101
Public Health; Epidemiology; Occupational & Industrial Medicine; Respiratory Medicine (see Thoracic Medicine); Statistics & Research Methods
14.  Common genetic variants in the 8q24 region and risk of papillary thyroid cancer 
The Laryngoscope  2012;122(5):1040-1042.
Single nucleotide polymorphisms (SNPs) in the 8q24 chromosomal region identified from genome-wide scans have been associated with risk of several cancers including breast (rs1562430), prostate and colon (rs1447295 and rs6983267). A genome-wide scan in 26 families with papillary thyroid cancer (PTC) also found susceptibility loci in 8q24, supporting a closer evaluation of this chromosomal region in relation to risk of sporadic PTC.
Study Design
We evaluated 157 tag SNPs in the 8q24 chromosomal region between 120.91 Mb and 128.78 Mb (including rs1562430, rs1447295, and rs6983267) in a case-control study of 344 PTC cases and 452 age and gender frequency-matched controls.
We used logistic regression to estimate odds ratios and compute P-values of linear trend for PTC with genotypes of interest. To account for multiple comparisons, we applied the false discovery rate (FDR) method.
We did not find a significant association between rs1562430, rs1447295, or rs6983267, and PTC risk. We found that one SNP (rs4733616) was associated with PTC risk at P = 0.003, and twelve other SNPs were associated with PTC risk at P < 0.05. However, no SNPs remained significant after FDR correction.
Our findings do not support a strong association between SNPs in the 8q24 chromosomal region and risk of sporadic PTC but several SNPs with small effects might exist.
PMCID: PMC3408055  PMID: 22275265
8q24; thyroid cancer
15.  Acetylcholinesterase Activity, Cohabitation with Floricultural Workers, and Blood Pressure in Ecuadorian Children 
Environmental Health Perspectives  2013;121(5):619-624.
Background: Acetylcholinesterase (AChE) inhibitors are commonly used pesticides that can effect hemodynamic changes through increased cholinergic stimulation. Children of agricultural workers are likely to have paraoccupational exposures to pesticides, but the potential physiological impact of such exposures is unclear.
Objectives: We investigated whether secondary pesticide exposures were associated with blood pressure and heart rate among children living in agricultural Ecuadorian communities.
Methods: This cross-sectional study included 271 children 4–9 years of age [51% cohabited with one or more flower plantation workers (mean duration, 5.2 years)]. Erythrocyte AChE activity was measured using the EQM Test-mate system. Linear regression models were used to estimate associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate with AChE activity, living with flower workers, duration of cohabitation with a flower worker, number of flower workers in the child’s home, and number of practices that might increase children’s exposure to pesticides.
Results: Mean (± SD) AChE activity was 3.14 ± 0.49 U/mL. A 1-U/mL decrease in AChE activity was associated with a 2.86-mmHg decrease in SBP (95% CI: –5.20, –0.53) and a 2.89-mmHg decrease in DBP (95% CI: –5.00, –0.78), after adjustment for potential confounders. Children living with flower workers had lower SBP (–1.72 mmHg; 95% CI: –3.53, 0.08) than other children, and practices that might increase exposure also were associated with lower SBP. No significant associations were found between exposures and heart rate.
Conclusions: Our findings suggest that subclinical secondary exposures to pesticides may affect vascular reactivity in children. Additional research is needed to confirm these findings.
PMCID: PMC3673186  PMID: 23359481
acetylcholinesterase; AChE; agricultural communities; agriculture; blood pressure; children; Ecuador; epidemiology; pesticides; secondary exposure
16.  Lower Acetylcholinesterase Activity among Children Living with Flower Plantation Workers 
Environmental Research  2012;114:53-59.
Children of workers exposed to pesticides are at risk of secondary pesticide exposure. We evaluated the potential for lower acetylcholinesterase activity in children cohabiting with fresh-cut flower plantation workers, which would be expected from organophosphate and carbamate insecticide exposure. Parental home surveys were performed and acetylcholinesterase activity was measured in 277 children aged 4–9 years in the study of Secondary Exposure to Pesticides among Infants, Children and Adolescents (ESPINA). Participants lived in a rural county in Ecuador with substantial flower plantation activity.
Mean acetylcholinesterase activity was 3.14 U/ml, standard deviation (SD): 0.49. It was lower by 0.09 U/ml (95% confidence interval (CI) −0.19, −0.001) in children of flower workers (57% of participants) than non-flower workers’ children, after adjustment for gender, age, height-for-age, hemoglobin concentration, income, pesticide use within household lot, pesticide use by contiguous neighbors, examination date and residence distance to nearest flower plantation. Using a 4 level polychotomous acetylcholinesterase activity dependent variable, flower worker cohabitation (vs. not) had odds ratio 3.39 (95% CI 1.19, 9.64) for being <15th percentile compared to the highest tertile. Children cohabitating for ≥5 years (vs. never) had OR of 4.11 (95% CI: 1.17, 14.38) of AChE activity within <15th percentile compared to the highest tertile.
Cohabitation with a flower worker was related to lower acetylcholinesterase activity in children. This supports the hypothesis that the amount of take-home pesticides from flower workers suffices to decrease acetylcholinesterase activity, with lower activity associated with longer exposure.
PMCID: PMC3319289  PMID: 22405996
Acetylcholinesterase; AChE; children; pesticide; organophosphate
17.  Individual, Environmental, and Meteorological Predictors of Daily Personal Ultraviolet Radiation Exposure Measurements in a United States Cohort Study 
PLoS ONE  2013;8(2):e54983.
Individual exposure to ultraviolet radiation (UVR) is challenging to measure, particularly for diseases with substantial latency periods between first exposure and diagnosis of outcome, such as cancer. To guide the choice of surrogates for long-term UVR exposure in epidemiologic studies, we assessed how well stable sun-related individual characteristics and environmental/meteorological factors predicted daily personal UVR exposure measurements.
We evaluated 123 United States Radiologic Technologists subjects who wore personal UVR dosimeters for 8 hours daily for up to 7 days (N = 837 days). Potential predictors of personal UVR derived from a self-administered questionnaire, and public databases that provided daily estimates of ambient UVR and weather conditions. Factors potentially related to personal UVR exposure were tested individually and in a model including all significant variables.
The strongest predictors of daily personal UVR exposure in the full model were ambient UVR, latitude, daily rainfall, and skin reaction to prolonged sunlight (R2 = 0.30). In a model containing only environmental and meteorological variables, ambient UVR, latitude, and daily rainfall were the strongest predictors of daily personal UVR exposure (R2 = 0.25).
In the absence of feasible measures of individual longitudinal sun exposure history, stable personal characteristics, ambient UVR, and weather parameters may help estimate long-term personal UVR exposure.
PMCID: PMC3566166  PMID: 23405102
18.  Mortality and cancer incidence in ammonium perfluorooctanoate production workers 
To evaluate mortality and cancer incidence in a cohort of ammonium perfluorooctanoate (APFO) exposed workers.
We linked a combined cohort (n=9027) of employees from APFO and non-APFO production facilities in Minnesota to the National Death Index and to cancer registries of Minnesota and Wisconsin. Industrial hygiene data and expert evaluation were used to create a task-based job exposure matrix to estimate APFO exposure. Standardised mortality ratios were estimated using Minnesota population rates. HRs and 95% CIs for time-dependent cumulative APFO exposure were estimated with an extended Cox model. A priori outcomes of interest included cancers of the liver, pancreas, testes, kidney, prostate and breast, and mortality from cardiovascular, cerebrovascular and chronic renal diseases.
Mortality rates in the APFO-exposed cohort were at or below the expected, compared with Minnesota. The HR for dying from the cancer and non-cancer outcomes of interest did not show an association with APFO exposure. Similarly, there was little evidence that the incident cancers were associated with APFO exposure. Compared to the non-exposed population, modestly elevated, but quite imprecise HRs were observed in the higher-exposure quartiles for bladder cancer (HR=1.66, 95% CI 0.86 to 3.18) and pancreatic cancer (HR=1.36, 95% CI 0.59 to 3.11). No association was observed between APFO exposure and kidney, prostate or breast cancers.
This analysis did not support an association between occupational APFO exposure and the evaluated health endpoints, however, the study had limited power to evaluate some conditions of interest.
PMCID: PMC4078701  PMID: 24832944
19.  Radiographic Evidence of Nonoccupational Asbestos Exposure from Processing Libby Vermiculite in Minneapolis, Minnesota 
Background: Community exposure to asbestos from contaminated vermiculite ore from Libby, Montana, occurred in many processing sites in the United States, including a densely populated urban residential neighborhood of Minneapolis, Minnesota.
Objective: We examined exposed community residents who never worked at the plant or never lived with a plant worker for radiographic evidence of lung changes consistent with asbestos exposure.
Methods: We obtained posteroanterior chest radiographs to identify the prevalence of pleural abnormalities consistent with pneumoconiosis, as determined by consensus of two National Institute for Occupational Safety and Health–certified B-reader radiologists. We estimated cumulative asbestos exposure (fibers per cubic centimeters × months) with air dispersion model data and activity-based modeled exposure estimates for vermiculite processing waste contact. We modeled associations between pleural abnormalities and asbestos exposure using multiple logistic regression to adjust for year of birth, sex, and potential occupational asbestos exposure.
Results: Radiographs were obtained for 461 participants. The prevalence of pleural abnormalities by B-reader consensus was 10.8%. A history of direct contact with the waste and ever playing in the waste piles was associated with pleural abnormalities {odds ratio [OR] 2.78 [95% confidence interval (CI): 1.26, 6.10] and 2.17 (95% CI: 0.99, 4.78), respectively, when adjusted for background exposure}. The regression coefficients for log-transformed measures (fibers per cubic centimeters × months) of background exposure and activity-based exposure were 0.322 (95% CI: 0.078, 0.567) and 0.063 (95% CI: –0.013, 0.139), respectively, when adjusted for each other, and 0.283 (95% CI: 0.104, 0.463) for cumulative exposure from all sources.
Conclusion: These results support the hypothesis that community exposure to asbestos-contaminated vermiculite originating from Libby, Montana, is associated with measurable effects based on radiographic evidence.
PMCID: PMC3261940  PMID: 21992801
amphibole; asbestos; community exposure; Libby vermiculite; lung diseases; pleural abnormalities
20.  Multiple Indicators of Ambient and Personal Ultraviolet Radiation Exposure and Risk of Non-Hodgkin Lymphoma (United States) 
Recent epidemiologic studies have suggested that ultraviolet radiation (UV) may protect against non-Hodgkin lymphoma (NHL), but few, if any, have assessed multiple indicators of ambient and personal UV exposure. Using the U.S. Radiologic Technologists study, we examined the association between NHL and self-reported time outdoors in summer, as well as average year-round and seasonal ambient exposures based on satellite estimates for different age periods, and sun susceptibility in participants who had responded to two questionnaires (1994-1998, 2003-2005) and who were cancer-free as of the earlier questionnaire. Using unconditional logistic regression, we estimated the odds ratio (OR) and 95% confidence intervals for 64,103 participants with 137 NHL cases. Self-reported time outdoors in summer was unrelated to risk. Lower risk was somewhat related to higher average year-round and winter ambient exposure for the period closest in time, and prior to, diagnosis (ages 20-39). Relative to 1.0 for the lowest quartile of average year-round ambient UV, the estimated OR for successively higher quartiles was 0.68 (0.42-1.10); 0.82 (0.52-1.29); and 0.64(0.40-1.03), p-trend = 0.06), for this age period. The lower NHL risk associated with higher year-round average and winter ambient UV provides modest additional support for a protective relationship between UV and NHL.
PMCID: PMC2963689  PMID: 20826094
21.  Sunlight, Hormone Replacement Status and Colorectal Cancer Risk in Post-Menopausal Women 
A reanalysis of the Women’s Health Initiative (WHI) randomized clinical trial found a significant interaction between supplementation with vitamin D/calcium and estrogen therapy and the risk of colorectal cancer risk, with reduced risks from supplementation limited to the placebo arms of the estrogen trials. To explore whether the vitamin D effects are modified by estrogen therapy, we report a largely cross-sectional, analysis of the association between sun exposure, which is an important vitamin D source, and colorectal cancer risk among postmenopausal women in the U.S. Radiologic Technologists study. Among 21,695 participants, there were a total of 108 cases. Sun exposure was based on time outdoors and on ambient ultraviolet radiation (UV) exposure based on residence linked to erythemal exposures derived from the Total Ozone Mapping Spectrometer (TOMS) database. Although there was no relationship between outdoor time or ambient UV measure and colorectal cancer risk in current hormone replacement therapy (HRT) users, in never/past HRT users, there was an inverse association with higher ambient UV exposure, RR for highest vs. lowest tertile=0.40; 95% CI 017, 0.93; p for trend = 0.04. Non-significant lower risks were also associated with higher levels of outdoor time (≥3.5 hours/week) in never/past HRT users. The interaction between both indicators of sun exposure and HRT and CRC risk was not significant. These data, although exploratory, are consistent with evidence from the WHI suggesting a decrease in colorectal cancer risk may be associated with vitamin D exposure among postmenopausal women who are not taking HRT, but not among current HRT users.
PMCID: PMC2829351  PMID: 19795420
22.  Polymorphisms in oxidative stress and inflammation pathway genes, low-dose ionizing radiation, and the risk of breast cancer among US radiologic technologists 
Cancer causes & control : CCC  2010;21(11):1857-1866.
Ionizing radiation, an established breast cancer risk factor, has been shown to induce oxidative damage and chronic inflammation. Polymorphic variation in oxidative stress and inflammatory-mediated pathway genes may modify radiation-related breast cancer risk.
We estimated breast cancer risk for 28 common variants in 16 candidate genes involved in these pathways among 859 breast cancer cases and 1,083 controls nested within the US Radiologic Technologists cohort. We estimated associations between occupational and personal diagnostic radiation exposures with breast cancer by modeling the odds ratio (OR) as a linear function in logistic regression models and assessed heterogeneity of the dose–response across genotypes.
There was suggestive evidence of an interaction between the rs5277 variant in PTGS2 and radiation-related breast cancer risk. The excess OR (EOR)/Gy from occupational radiation exposure = 5.5 (95%CI 1.2–12.5) for the GG genotype versus EOR/Gy < 0 (95%CI < 0–3.8) and EOR/Gy < 0 (95%CI < 0–14.8) for the GC and CC genotypes, respectively, (pinteraction = 0.04). The association between radiation and breast cancer was not modified by other SNPs examined.
This study suggests that variation in PTGS2 may modify the breast cancer risk from occupational radiation exposure, but replication in other populations is needed to confirm this result.
PMCID: PMC3076104  PMID: 20711808
PTGS2; COX-2; Inflammation; Breast cancer; Radiation
23.  Novel breast cancer risk alleles and interaction with ionizing radiation among U.S. Radiologic Technologists 
Radiation research  2010;173(2):214-224.
As genome-wide association studies of breast cancer are replicating findings and refinement studies are narrowing the signal location, additional efforts are necessary to elucidate the underlying functional relationships. One approach is to evaluate variation in risk by genotype based on known breast carcinogens, such as ionizing radiation. Given the public health concerns associated with recent increases in medical radiation exposure, this approach may also identify potentially susceptible sub-populations. We examined interaction between 27 newly identified breast cancer risk alleles (identified within the NCI Cancer Genetic Markers of Susceptibility and the Breast Cancer Association Consortium genome-wide association studies) and occupational and medical diagnostic radiation exposure among 859 cases and 1083 controls nested within the United States Radiologic Technologists cohort. We did not find significant variation in the radiation-related breast cancer risk for the variant in RAD51L1 (rs10483813) on 14q24.1 as we had hypothesized. In exploratory analyses, we found that the radiation-associated breast cancer risk varied significantly by linked markers in 5p12 (rs930395, rs10941679, rs2067980, and rs4415084) in the mitochondrial ribosomal protein S30 (MRPS30) gene (pinteraction=0.04). Chance, however, may explain these findings, and as such, these results need to be confirmed in other populations with low to moderate levels of radiation exposure. Even though a complete understanding by which these variants may increase breast cancer risk remains elusive, this approach may yield clues for further investigation.
PMCID: PMC2922870  PMID: 20095854
24.  Nonradiation Risk Factors for Thyroid Cancer in the US Radiologic Technologists Study 
American Journal of Epidemiology  2009;171(2):242-252.
The incidence of thyroid cancer has been rapidly increasing in the United States, but few risk factors have been established. The authors prospectively examined the associations of self-reported medical history, anthropometric factors, and behavioral factors with thyroid cancer risk among 90,713 US radiologic technologists (69,506 women and 21,207 men) followed from 1983 through 2006. Incident thyroid cancers in 242 women and 40 men were reported. Elevated risks were observed for women with benign thyroid conditions (hazard ratio (HR) = 2.35, 95% confidence interval (CI): 1.73, 3.20), benign breast disease (HR = 1.56, 95% CI: 1.08, 2.26), asthma (HR = 1.68, 95% CI: 1.00, 2.83), and body mass index ≥35.0 versus 18.5–24.9 kg/m2 (HR = 1.74, 95% CI: 1.03, 2.94; P-trend = 0.04). Current smoking was inversely associated with thyroid cancer risk (HR = 0.54). No clear associations emerged for reproductive factors, other medical conditions, alcohol intake, or physical activity. Despite few thyroid cancers in men, men with benign thyroid conditions had a significantly increased risk of thyroid cancer (HR = 4.65, 95% CI: 1.62, 13.34), and results for other risk factors were similar to those for women. Consistent with prior studies, obesity and benign thyroid conditions increased and current smoking decreased the risk of thyroid cancer. The novel findings for benign breast disease and asthma warrant further investigation.
PMCID: PMC3290908  PMID: 19951937
body mass index; hormones; motor activity; prospective studies; reproduction; smoking; thyroid diseases; thyroid neoplasms
Ionizing radiation-associated breast cancer risk appears to be modified by timing of reproductive events such as age at radiation exposure, parity, age at first live birth, and age at menopause. However, potential breast cancer risk modification of low- to moderate radiation dose by polymorphic estrogen metabolism-related gene variants has not been routinely investigated. We assessed breast cancer risk of 12 candidate variants in 12 genes involved in steroid metabolism, catabolism, binding, or receptor functions in a study of 859 cases and 1083 controls within the US Radiologic Technologists (USRT) cohort. Using cumulative breast dose estimates from a detailed assessment of occupational and personal diagnostic ionizing radiation exposure, we investigated the joint effects of genotype on the risk of breast cancer. In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the CYP3A4 M445T minor allele (rs4986910, OR=0.3; 95% CI 0.1–0.9). We found a borderline increased breast cancer risk with having both minor alleles of CYP1B1 V432L (rs1056836, CC vs. GG, OR=1.2; 95% CI 0.9–1.6). Assuming a recessive model, the minor allele of CYP1B1 V432L significantly increased the dose-response relationship between personal diagnostic x-ray exposure and breast cancer risk, adjusted for cumulative occupational radiation dose (pinteraction=0.03) and had a similar joint effect for cumulative occupational radiation dose adjusted for personal diagnostic x-ray exposure (pinteraction=0.06). We found suggestive evidence that common variants in selected estrogen metabolizing genes may modify the association between ionizing radiation exposure and breast cancer risk.
PMCID: PMC2860373  PMID: 19214745

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