Do airline pilots and cabin crew have raised risks of melanoma and other skin cancers? Systematic review and meta-analysis Kyoko Miura1*, Catherine M Olsen1*, Stephanie Rea1, Jeremy Marsden2, Adèle C Green1,3   1 Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland, 4006 Australia 2 Queen Elizabeth Hospital, Birmingham B15 2GW, UK 3 CRUK Manchester Institute and Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK * KM and CMO contributed equally to this work British Journal of Dermatology. DOI: 10.111/bjd.17586

This project was lead by Professor Adèle C Green

Introduction What’s already known? Airline pilots are exposed to cosmic and ultraviolet (UV) radiation in their occupations and cabin crews are occupationally exposed to cosmic radiation Airline pilots and cabin crews appear to be at significantly increased risk of developing melanoma Pilots are at increased risk of dying from melanoma

Objective To establish precise risks of melanoma and keratinocyte cancer (KC) for airline pilots and for cabin crew based on all studies published to date

Methods Searched Medline, ISI science citation index, EMBASE, SCOPUS, and CINAHL to June 2018 Inclusion prospective and retrospective cohort studies any language incidence of or mortality from melanoma or KC (i.e. BCC or SCC) in airline pilots or cabin crew compared with the general population studies with histological confirmation of melanoma for mortality, record linkage (ICD codes), death registries, death certificates, and physician records

Methods continued Multiple reports from the same population or subpopulation included the report with the longest follow-up or the most comprehensive data Data extraction Two reviewers independently abstracted data study design, location, years of data collection, sources and definition of cohort, definition of exposure (e.g. flying hours, radiation dose), No. of cases, person-year of follow-up, age of the study population, variables used for statistical adjustment, point estimates (odds ratio, hazard ratio or standardized incidence or mortality ratio) and 95% CIs Quality assessment – Newcastle-Ottawa Quality Assessment

Methods: Data synthesis & analysis DerSimonian and Laird: a random-effects model Pooled standardised incidence ratios (pSIR) and pooled standardised mortality ratios (pSMR) with 95% CI Statistical heterogeneity among studies – Q-statistic inconsistencies were quantified using the I2 statistic. Sensitivity analyses – excluding each study in turn to examine the effect on the pooled estimate. Publication bias – visual inspection of funnel plots + Begg’s & Egger’s tests STATA (version 15)

Results Identified 5866 articles, assessed 44 full-text, 12 studies included in quantitative synthesis Published between 1990–2017 3 studies were based in North America, 5 in Europe, 4 were multinational retrospective cohort = 10 studies retrospective & prospective cohort = 2 studies Newcastle-Ottawa Quality Assessment Scale (ranges 0–9) 7 studies = scored 7 4 studies = scored 6 1 study = scored 5 higher score = better quality

Results: Melanoma Pilots Cabin crew incidence: 7 studies pooled SIR (pSIR) 2.03 (95% CI 1.71–2.40) no evidence of heterogeneity (I2=0.0%, p=0.84); no evidence of publication bias (Begg p=0.76; Egger p=0.66) mortality: 3 studies pSMR 1.99 (95% CI 1.17–3.40) no evidence of heterogeneity (I2=41.6%, p=0.18); no evidence of publication bias (Begg p=0.60; Egger p=0.75) Cabin crew incidence: 2 studies reported pSIR 2.12 (95% CI 1.71–2.62) no evidence of heterogeneity (I2=0.0%, p=0.55) mortality: 1 study SMR 1.18 (95% CI 0.73–1.89)

Results: Keratinocyte cancer (KC) Pilots Incidence BCC (1 study) SIR 2.46 (95% CI 1.88–3.16) KC (4 studies) pSIR 1.86 (95% CI 1.54–2.25) No evidence of heterogeneity (I2=1.4%, p=0.39); no evidence of publication bias (Begg p=0.73; Egger p=0.16) Mortality KC (1 study) SMR 0.93 (95% CI 0.15–3.04) Cabin crew BCC (1 study) SIR 2.33 (95% CI 1.77–3.01) KC (1 study) SIR 1.97 (95% CI 1.25–2.96) KC (1 study) SMR 8.01 (95% CI 2.98–17.33) KC: Keratinocyte cancer

Discussion Airline pilots Compared with the general population: risk of melanoma & keratinocyte skin cancers ≈ ↑ 2 x risk of dying from melanoma ≈ ↑ 2 x, but not KC Cabin crew Risk of melanoma & keratinocyte skin cancers ≈ ↑ 2 x Risk of dying from melanoma was similar to the general population

Discussion continued UV-B from the sun – main environmental cause of melanoma & skin cancer Occupational UV exposure Cabins Flight deck UV-A levels in flight deck in the 20th century – unknown almost all reviewed evidence is out-of-date (studied in the mid- to late 20th century) → limitations Cosmic radiation elevated in pilots and cabin crew but below hazardous level → unlikely the cause UV-B radiation is not detectable or not increased above ground level values in modern airline cabins and flight decks

Discussion continued Circadian rhythm disruption – carcinogenic melanoma + skin cancer from short-haul routes → unlikely the cause Recreational UV-exposure among pilots & cabin crews during recreational activities including during stopovers absence of direct evidence but cannot be ruled out

Conclusions What does this study add? Risk of melanoma and other skin cancer is approximately doubled in airline pilots and cabin crew compared with the population; occupational exposure to ultraviolet radiation is unlikely to explain the raised risk Causal roles of occupational exposure to ionising radiation, and recreational exposure to ultraviolet radiation, are plausible but there is little supporting evidence Almost all relevant evidence is out-of-date and is restricted to the Northern Hemisphere: research is needed that better reflects the occupational environment and recreational behaviour of current pilots and cabin crews

Research team K. Miura C. Olsen S. Rea J. Marsden A. Green