Cancer incidence among 10,211 airline pilots: a Nordic study

BACKGROUND: Commercial airline pilots are exposed to cosmic radiation and other potentially carcinogenic elements during work and leisure activities. HYPOTHESIS: Work-related factors affect cancer pattern of the pilots. METHODS: A cohort of 10,051 male and 160 female airline pilots from Denmark, Finland, Iceland, Norway, and Sweden was followed for cancer incidence through the national cancer registries. There were 177,000 person-years at follow-up, 51,000 of them accumulated after 20 yr since the time of first employment. Standardized incidence ratios (SIRs) were defined as ratios of observed over expected numbers of cases based on national cancer incidence rates. Dose-response analyses were done with Poisson regression method. RESULTS: Among male pilots, there were 466 cases of cancer diagnosed vs. 456 expected. The only significantly increased SIRs concerned skin cancer: melanoma 2.3 (95% CI 1.7-3.0), squamous cell cancer 2.1 (1.7-2.8), and basal cell carcinoma 2.5 (1.9-3.2). The relative risk of skin cancers increased with the time since first employment, the number of flight hours, and the estimated radiation dose. There was an increase in the relative risk of prostate cancer with increasing number of flight hours in long-distance aircraft (p trend 0.01). No increased incidence was found for acute myeloid leukemia or brain cancer which were of interest a priori based on earlier studies. CONCLUSIONS: This large study, based on reliable cancer incidence data, showed an increased incidence of skin cancer. It did not indicate a marked increase in cancer risk attributable to cosmic radiation although some influence of cosmic radiation on skin cancer cannot be entirely excluded

Cancer incidence among 10,211 airline pilots: a Nordic study

BACKGROUND: Commercial airline pilots are exposed to cosmic radiation and other potentially carcinogenic elements during work and leisure activities. HYPOTHESIS: Work-related factors affect cancer pattern of the pilots. METHODS: A cohort of 10,051 male and 160 female airline pilots from Denmark, Finland, Iceland, Norway, and Sweden was followed for cancer incidence through the national cancer registries. There were 177,000 person-years at follow-up, 51,000 of them accumulated after 20 yr since the time of first employment. Standardized incidence ratios (SIRs) were defined as ratios of observed over expected numbers of cases based on national cancer incidence rates. Dose-response analyses were done with Poisson regression method. RESULTS: Among male pilots, there were 466 cases of cancer diagnosed vs. 456 expected. The only significantly increased SIRs concerned skin cancer: melanoma 2.3 (95% CI 1.7-3.0), squamous cell cancer 2.1 (1.7-2.8), and basal cell carcinoma 2.5 (1.9-3.2). The relative risk of skin cancers increased with the time since first employment, the number of flight hours, and the estimated radiation dose. There was an increase in the relative risk of prostate cancer with increasing number of flight hours in long-distance aircraft (p trend 0.01). No increased incidence was found for acute myeloid leukemia or brain cancer which were of interest a priori based on earlier studies. CONCLUSIONS: This large study, based on reliable cancer incidence data, showed an increased incidence of skin cancer. It did not indicate a marked increase in cancer risk attributable to cosmic radiation although some influence of cosmic radiation on skin cancer cannot be entirely excluded

Mortality from cancer and other causes among airline cabin attendants in Europe: a collaborative cohort study in eight countries

There is concern about the health effects of exposure to cosmic radiation during air travel. To study the potential health effects of this and occupational exposures, the authors investigated mortality patterns among more than 44,000 airline cabin crew members in Europe. A cohort study was performed in eight European countries, yielding approximately 655,000 person-years of follow-up. Observed numbers of deaths were compared with expected numbers based on national mortality rates. Among female cabin crew, overall mortality (standardized mortality ratio (SMR) = 0.80, 95% confidence interval (CI): 0.73, 0.88) and all-cancer mortality (SMR = 0.78, 95% CI: 0.66, 0.95) were slightly reduced, while breast cancer mortality was slightly but nonsignificantly increased (SMR = 1.11, 95% CI: 0.82, 1.48). In contrast, overall mortality (SMR = 1.09, 95% CI: 1.00, 1.18) and mortality from skin cancer (for malignant melanoma, SMR = 1.93, 95% CI: 0.70, 4.44) among male cabin crew were somewhat increased. The authors noted excess mortality from aircraft accidents and from acquired immunodeficiency syndrome in males. Among airline cabin crew in Europe, there was no increase in mortality that could be attributed to cosmic radiation or other occupational exposures to any substantial extent. The risk of skin cancer among male crew members requires further attention

Genotype-phenotype correlations and novel molecular insights into the DHX30-associated neurodevelopmental disorders.

BACKGROUND We aimed to define the clinical and variant spectrum and to provide novel molecular insights into the DHX30-associated neurodevelopmental disorder. METHODS Clinical and genetic data from affected individuals were collected through Facebook-based family support group, GeneMatcher, and our network of collaborators. We investigated the impact of novel missense variants with respect to ATPase and helicase activity, stress granule (SG) formation, global translation, and their effect on embryonic development in zebrafish. SG formation was additionally analyzed in CRISPR/Cas9-mediated DHX30-deficient HEK293T and zebrafish models, along with in vivo behavioral assays. RESULTS We identified 25 previously unreported individuals, ten of whom carry novel variants, two of which are recurrent, and provide evidence of gonadal mosaicism in one family. All 19 individuals harboring heterozygous missense variants within helicase core motifs (HCMs) have global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities. These variants impair the ATPase and helicase activity of DHX30, trigger SG formation, interfere with global translation, and cause developmental defects in a zebrafish model. Notably, 4 individuals harboring heterozygous variants resulting either in haploinsufficiency or truncated proteins presented with a milder clinical course, similar to an individual harboring a de novo mosaic HCM missense variant. Functionally, we established DHX30 as an ATP-dependent RNA helicase and as an evolutionary conserved factor in SG assembly. Based on the clinical course, the variant location, and type we establish two distinct clinical subtypes. DHX30 loss-of-function variants cause a milder phenotype whereas a severe phenotype is caused by HCM missense variants that, in addition to the loss of ATPase and helicase activity, lead to a detrimental gain-of-function with respect to SG formation. Behavioral characterization of dhx30-deficient zebrafish revealed altered sleep-wake activity and social interaction, partially resembling the human phenotype. CONCLUSIONS Our study highlights the usefulness of social media to define novel Mendelian disorders and exemplifies how functional analyses accompanied by clinical and genetic findings can define clinically distinct subtypes for ultra-rare disorders. Such approaches require close interdisciplinary collaboration between families/legal representatives of the affected individuals, clinicians, molecular genetics diagnostic laboratories, and research laboratories