Chromosome Translocations and Cosmic Radiation Dose in Male U.S. Commercial Airline Pilots.

BACKGROUND: Chromosome translocations are a biomarker of cumulative exposure to ionizing radiation. We examined the relation between the frequency of translocations and cosmic radiation dose in 83 male airline pilots. METHODS: Translocations were scored using fluorescence in situ hybridization chromosome painting. Cumulative radiation doses were estimated from individual flight records. Excess rate and log-linear Poisson regression models were evaluated. RESULTS: Pilots' estimated median cumulative absorbed dose was 15 mGy (range 4.5-38). No association was observed between translocation frequency and absorbed dose from all types of flying [rate ratio (RR) = 1.01 at 1 mGy, 95% confidence interval (CI) 0.97-1.04]. However, additional analyses of pilots' dose from only commercial flying suggested an association (RR = 1.04 at 1 mGy, 95% CI 0.97-1.13). DISCUSSION: Although this is the largest cytogenetic study of male commercial airline pilots to date of which the authors are aware, future studies will need additional highly exposed pilots to better assess the translocation-cosmic radiation relation.Grajewski B, Yong LC, Bertke SJ, Bhatti P, Little MP, Ramsey MJ, Tucker JD, Ward EM, Whelan EA, Sigurdson AJ, Waters MA. Chromosome translocations and cosmic radiation dose in male U.S. commercial airline pilots. Aerosp Med Hum Perform. 2018; 89(7):616-625.

Sleep-related problems in the US working population: prevalence and association with shiftwork status.

OBJECTIVE: To estimate the prevalence of a comprehensive set of self-reported sleep problems by job characteristics, including shiftwork status, among a representative sample of US workers. METHODS: Data for 6338 workers aged ≥18 years were obtained from the National Health and Nutrition Examination Survey. Short sleep duration was defined as <7 hours per weekday/workday. Sleep quality was categorised as good, moderate and poor based on the frequency of 6 sleep-related symptoms. A sleep-related activities of daily living (ADL) score ≥2 was defined as impaired. Insomnia was defined as having poor sleep quality and impaired ADL. Shiftwork status was categorised as daytime, night, evening, rotating or another schedule. Prevalence rates were calculated and multivariate logistic regression analyses were used. RESULTS: The prevalence of short sleep duration (37.6% overall) was highest among night shift workers (61.8%; p<0.001). The prevalence of poor sleep quality was 19.2% among all workers, with the highest prevalence among night shift workers (30.7%, p=0.004). The prevalence of impaired ADL score (24.8% overall) and insomnia (8.8% overall) was also highest for night shift workers (36.2%, p=0.001 and 18.5%, p=0.013, respectively). In multivariate analysis, night shift workers had the highest likelihood of these sleep problems. CONCLUSIONS: Self-reported short sleep duration, poor sleep quality, impaired ADL score and insomnia are common among US workers especially among night shift workers. Although these findings should be confirmed with objective sleep measures, they support the need for intervention programmes to improve sleep quantity and quality among night shift workers.

Mortality among a cohort of U.S. commercial airline cockpit crew.

BACKGROUND: We evaluated mortality among 5,964 former U.S. commercial cockpit crew (pilots and flight engineers). The outcomes of a priori interest were non-chronic lymphocytic leukemia, central nervous system (CNS) cancer (including brain), and malignant melanoma. METHODS: Vital status was ascertained through 2008. Life table and Cox regression analyses were conducted. Cumulative exposure to cosmic radiation was estimated from work history data. RESULTS: Compared to the U.S. general population, mortality from all causes, all cancer, and cardiovascular diseases was decreased, but mortality from aircraft accidents was highly elevated. Mortality was elevated for malignant melanoma but not for non-chronic lymphocytic leukemia. CNS cancer mortality increased with an increase in cumulative radiation dose. CONCLUSIONS: Cockpit crew had a low all-cause, all-cancer, and cardiovascular disease mortality but elevated aircraft accident mortality. Further studies are needed to clarify the risk of CNS and other radiation-associated cancers in relation to cosmic radiation and other workplace exposures.

Quit interest, quit attempt and recent cigarette smoking cessation in the US working population, 2010.

OBJECTIVES: To determine the prevalence of cigarette smoking cessation and examine the association between cessation and various factors among workers in a nationally representative sample of US adults. METHODS: Data were derived from the 2010 National Health Interview Survey. Prevalence rates were calculated for interest in quitting smoking, making an attempt to quit smoking, and successful smoking cessation (defined as smokers who had quit for 6-12 months). Logistic regression analyses were used to identify factors associated with cessation after adjustment for demographic characteristics (age group, race/ethnicity, educational level and marital status). RESULTS: Data were available for 17 524 adults who were employed in the 12 months prior to interview. The prevalence of quit interest, quit attempt and recent cessation was 65.2%, 53.8% and 6.8%, respectively. Quit interest was less likely among workers with long work hours, but more likely among workers with job insecurity, or frequent workplace skin and/or respiratory exposures. Quit attempt was more likely among workers with a hostile work environment but less likely among workers living in a home that permitted smoking or who smoked ≥11 cigarettes/day. Recent smoking cessation was less likely among workers with frequent exposure to others smoking at work or living in a home that permitted smoking, but more likely among workers with health insurance. CONCLUSIONS: Factors associated with cessation interest or attempt differed from those associated with successful cessation. Cessation success might be improved by reducing exposure to others smoking at work and home, and by improving access to health insurance.

Airline pilot cosmic radiation and circadian disruption exposure assessment from logbooks and company records.

OBJECTIVES: US commercial airline pilots, like all flight crew, are at increased risk for specific cancers, but the relation of these outcomes to specific air cabin exposures is unclear. Flight time or block (airborne plus taxi) time often substitutes for assessment of exposure to cosmic radiation. Our objectives were to develop methods to estimate exposures to cosmic radiation and circadian disruption for a study of chromosome aberrations in pilots and to describe workplace exposures for these pilots. METHODS: Exposures were estimated for cosmic ionizing radiation and circadian disruption between August 1963 and March 2003 for 83 male pilots from a major US airline. Estimates were based on 523 387 individual flight segments in company records and pilot logbooks as well as summary records of hours flown from other sources. Exposure was estimated by calculation or imputation for all but 0.02% of the individual flight segments' block time. Exposures were estimated from questionnaire data for a comparison group of 51 male university faculty. RESULTS: Pilots flew a median of 7126 flight segments and 14 959 block hours for 27.8 years. In the final study year, a hypothetical pilot incurred an estimated median effective dose of 1.92 mSv (absorbed dose, 0.85 mGy) from cosmic radiation and crossed 362 time zones. This study pilot was possibly exposed to a moderate or large solar particle event a median of 6 times or once every 3.7 years of work. Work at the study airline and military flying were the two highest sources of pilot exposure for all metrics. An index of work during the standard sleep interval (SSI travel) also suggested potential chronic sleep disturbance in some pilots. For study airline flights, median segment radiation doses, time zones crossed, and SSI travel increased markedly from the 1990s to 2003 (P(trend) < 0.0001). Dose metrics were moderately correlated with records-based duration metrics (Spearman's r = 0.61-0.69). CONCLUSIONS: The methods developed provided an exposure profile of this group of US airline pilots, many of whom have been exposed to increasing cosmic radiation and circadian disruption from the 1990s through 2003. This assessment is likely to decrease exposure misclassification in health studies.

High dietary niacin intake is associated with decreased chromosome translocation frequency in airline pilots.

Experimental studies suggest that B vitamins such as niacin, folate, riboflavin, vitamin B6 and vitamin B12 may protect against DNA damage induced by ionising radiation (IR). However, to date, data from IR-exposed human populations are not available. We examined the intakes of these B vitamins and their food sources in relation to the frequency of chromosome translocations as a biomarker of cumulative DNA damage, in eighty-two male airline pilots. Dietary intakes were estimated by using a self-administered semi-quantitative FFQ. Translocations in peripheral blood lymphocytes were scored by using fluorescence in situ hybridisation whole-chromosome painting. Negative binomial regression was used to estimate rate ratios and 95 % CI, adjusted for age and occupational and lifestyle factors. We observed a significant inverse association between translocation frequency and dietary intake of niacin (P = 0·02): adjusted rate ratio for subjects in the highest tertile compared with the lowest tertile was 0·58 (95 % CI 0·40, 0·83). Translocation frequency was not associated with total niacin intake from food and supplements as well as dietary or total intake of folate, riboflavin or vitamin B6 or B12. However, the adjusted rate ratios were significant for subjects with ≥ median compared with < median intake of whole grains (P = 0·03) and red and processed meat (P = 0·01): 0·69 (95 % CI 0·50, 0·96) and 1·56 (95 % CI 1·13, 2·16), respectively. Our data suggest that a high intake of niacin from food or a diet high in whole grains but low in red and processed meat may protect against cumulative DNA damage in IR-exposed persons.

Diagnostic X-ray examinations and increased chromosome translocations: evidence from three studies.

Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.

High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots.

BACKGROUND: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. OBJECTIVE: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. DESIGN: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. RESULTS: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, beta-carotene, beta-cryptoxanthin, and lutein-zeaxanthin from food (P < 0.05). Translocation frequency was not associated with the intake of vitamin E, alpha-carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for > or =median compared with or =median compared with

Occupational exposure to polychlorinated biphenyls and risk of breast cancer.

BACKGROUND: Despite the endocrine system activity exhibited by polychlorinated biphenyls (PCBs), recent studies have shown little association between PCB exposure and breast cancer mortality. OBJECTIVES: To further evaluate the relation between PCB exposure and breast cancer risk, we studied incidence, a more sensitive end point than mortality, in an occupational cohort. METHODS: We followed 5,752 women employed for at least 1 year in one of three capacitor manufacturing facilities, identifying cases from questionnaires, cancer registries, and death certificates through 1998. We collected lifestyle and reproductive information via questionnaire from participants or next of kin and used semiquantitative job-exposure matrices for inhalation and dermal exposures combined. We generated standardized incidence ratios (SIRs) and standardized rate ratios and used Cox proportional hazards regression models to evaluate potential confounders and effect modifiers. RESULTS: Overall, the breast cancer SIR was 0.81 (95% confidence interval, 0.72-0.92; n = 257), and regression modeling showed little effect of employment duration or cumulative exposure. However, for the 362 women of questionnaire-identified races other than white, we observed positive, statistically significant associations with employment duration and cumulative exposure; only smoking, birth cohort, and self- or proxy questionnaire completion had statistically significant explanatory power when added to models with exposure metrics. CONCLUSIONS: We found no overall elevation in breast cancer risk after occupational exposure to PCBs. However, the exposure-related risk elevations seen among nonwhite workers, although of limited interpretability given the small number of cases, warrant further investigation, because the usual reproductive risk factors accounted for little of the increased risk.

Routine diagnostic X-ray examinations and increased frequency of chromosome translocations among U.S. radiologic technologists.

The U.S. population has nearly one radiographic examination per person per year, and concern about cancer risks associated with medical radiation has increased. Radiologic technologists were surveyed to determine whether their personal cumulative exposure to diagnostic X-rays was associated with increased frequencies of chromosome translocations, an established radiation biomarker and possible intermediary suggesting increased cancer risk. Within a large cohort of U.S. radiologic technologists, 150 provided a blood sample for whole chromosome painting and were interviewed about past X-ray examinations. The number and types of examinations reported were converted to a red bone marrow (RBM) dose score with units that approximated 1 mGy. The relationship between dose score and chromosome translocation frequency was assessed using Poisson regression. The estimated mean cumulative RBM radiation dose score was 49 (range, 0-303). After adjustment for age, translocation frequencies significantly increased with increasing RBM dose score with an estimate of 0.004 translocations per 100 cell equivalents per score unit (95% confidence interval, 0.002-0.007; P < 0.001). Removing extreme values or adjustment for gender, cigarette smoking, occupational radiation dose, allowing practice X-rays while training, work with radioisotopes, and radiotherapy for benign conditions did not affect the estimate. Cumulative radiation exposure from routine X-ray examinations was associated independently with increased chromosome damage, suggesting the possibility of elevated long-term health risks, including cancer. The slope estimate was consistent with expectation based on cytogenetic experience and atomic bomb survivor data.

International study of factors affecting human chromosome translocations.

Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p<0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR)=1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes.

Retrospective biodosimetry among United States radiologic technologists.

Measurement of chromosome translocations in peripheral blood lymphocytes has been used to quantify prior exposure to ionizing radiation, including for workers exposed to low, chronic doses. We assessed translocation frequencies in a subset of U.S. radiologic technologists to substantiate ionizing radiation dose estimates developed for 110,418 technologists who worked between 1916 and 1984. From 3,441 cohort members known to have begun working before 1950, we selected a sample of 152, stratified by estimated cumulative dose, over-sampling from higher-dose categories and excluding persons with a prior cancer diagnosis, a personal or family history of chromosomal instability disorders, or a current history of smoking. Estimates of film-badge dose ranged from less than 10 cSv to more than 30 cSv. Blood samples, obtained in 2004, were analyzed by fluorescence in situ hybridization (FISH) whole chromosome painting by simultaneously labeling chromosomes 1, 2 and 4 in red and 3, 5 and 6 in green. Translocations were scored in 1800 well-spread metaphase cells and expressed per 100 cell equivalents (CE) per person. Linear Poisson regression models with allowance for overdispersion were used to assess the relationship between estimated occupational red bone marrow absorbed dose in cGy and translocation frequency, adjusted for age, gender and estimated red bone marrow absorbed dose score from personal diagnostic procedures. We observed 0.09 excess translocations per 100 CE per cGy red bone marrow dose (95% CI: -0.01, 0.2; P = 0.07), which is similar to the expected estimate based on previous cytogenetic studies (0.05 excess translocations per 100 CE per cGy). Despite uncertainty in the estimates of occupational red bone marrow absorbed doses, we found good general agreement between the doses and translocation frequencies, lending support to the credibility of the dose assessment for this large cohort of U.S. radiologic technologists.

DNA adducts in granulocytes of hospital workers exposed to ethylene oxide.

BACKGROUND: Ethylene oxide (EtO), an important industrial chemical intermediate and sterilant, is classified as a human carcinogen. Occupational EtO exposure in many countries is regulated at 1 ppm (8-hr TWA), but levels of EtO-DNA adducts in humans with low occupational EtO exposures have not been reported. METHODS: We examined the formation of N7-(2'-hydroxyethyl)guanine (N7-HEG), a major DNA adduct of EtO, in 58 EtO-exposed sterilizer operators and six nonexposed workers from ten hospitals. N7-HEG was quantified in granulocyte DNA (0.1-11.5 microg) by a highly sensitive and specific gas chromatography-electron capture-mass spectrometry method. Cumulative exposure to EtO (ppm-hour) was estimated during the 4-month period before the collection of blood samples. RESULTS: There was considerable inter-individual variability in the levels of N7-HEG with a range of 1.6-241.3 adducts/10(7) nucleotides. The mean levels in the nonexposed, low (< or =32 ppm-hour), and high (>32 ppm-hour) EtO-exposure groups were 3.8, 16.3, and 20.3 adducts/10(7) nucleotides, respectively, after the adjustment for cigarette smoking and other potential confounders, but the differences were not statistically significant. CONCLUSIONS: This study has demonstrated for the first time, detectable levels of N7-HEG adducts in granulocytes of hospital workers with EtO exposures at levels less than the current U.S. standard of 1 ppm (8-hr TWA). A nonsignificant increase in adduct levels with increasing EtO exposure indicates that further studies of EtO-exposed workers are needed to clarify the relationship between EtO exposure and N7-HEG adduct formation.

Lung cancer incidence in never smokers.

PURPOSE: Lung cancer is a leading cause of cancer death worldwide. Although smoking remains the predominant cause of lung cancer, lung cancer in never smokers is an increasingly prominent public health issue. However, data on this topic, particularly lung cancer incidence rates in never smokers, are limited. METHODS: We reviewed the existing literature on lung cancer incidence and mortality rates among never smokers and present new data regarding rates in never smokers from the following large, prospective cohorts: Nurses' Health Study; Health Professionals Follow-Up Study; California Teachers Study; Multiethnic Cohort Study; Swedish Lung Cancer Register in the Uppsala/Orebro region; and First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study. RESULTS: Truncated age-adjusted incidence rates of lung cancer among never smokers age 40 to 79 years in these six cohorts ranged from 14.4 to 20.8 per 100,000 person-years in women and 4.8 to 13.7 per 100,000 person-years in men, supporting earlier observations that women are more likely than men to have non-smoking-associated lung cancer. The distinct biology of lung cancer in never smokers is apparent in differential responses to epidermal growth factor receptor inhibitors and an increased prevalence of adenocarcinoma histology in never smokers. CONCLUSION: Lung cancer in never smokers is an important public health issue, and further exploration of its incidence patterns, etiology, and biology is needed.