Germline Elongator mutations in Sonic Hedgehog medulloblastoma.

Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children1,2, and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma3. Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHHα subtype4 and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U34) position5,6. Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems7-9. Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.

Occupation and tongue cancer in Nordic countries.

PURPOSE: Almost 200,000 tongue cancers were diagnosed worldwide in 2020. The aim of this study was to describe occupational risk variation in this malignancy. METHODS: The data are based on the Nordic Occupational Cancer (NOCCA) study containing 14.9 million people from the Nordic countries with 9020 tongue cancers diagnosed during 1961-2005. The standardized incidence ratio (SIR) of tongue cancer in each occupational category was calculated using national incidence rates as the reference. RESULTS: Among men, the incidence was statistically significantly elevated in waiters (SIR 4.36, 95% confidence interval (CI) 3.13--5.92), beverage workers (SIR 3.42, 95% CI 2.02-5.40), cooks and stewards (SIR 2.55, 95% CI 1.82-3.48), seamen (SIR 1.66, 95% CI 1.36-2.00), journalists (SIR 1.85, 95% CI 1.18-2.75), artistic workers (SIR 2.05, 95% CI 1.54-2.66), hairdressers (SIR 2.17, 95% CI 1.39-3.22), and economically inactive persons (SIR 1.57, 95% CI 1.42-1.73). Among women, the SIR was statistically significantly elevated only in waitresses (SIR 1.39, 95% CI 1.05-1.81). Statistically significant SIRs ≤ 0.63 were observed in male farmers, gardeners, forestry workers and teachers, and in female launderers. CONCLUSIONS: These findings may be related to consumption of alcohol and tobacco, but the effect of carcinogenic exposure from work cannot be excluded.

Brain cancer after radiation exposure from CT examinations of children and young adults: results from the EPI-CT cohort study.

BACKGROUND: The European EPI-CT study aims to quantify cancer risks from CT examinations of children and young adults. Here, we assess the risk of brain cancer. METHODS: We pooled data from nine European countries for this cohort study. Eligible participants had at least one CT examination before age 22 years documented between 1977 and 2014, had no previous diagnosis of cancer or benign brain tumour, and were alive and cancer-free at least 5 years after the first CT. Participants were identified through the Radiology Information System in 276 hospitals. Participants were linked with national or regional registries of cancer and vital status, and eligible cases were patients with brain cancers according to WHO International Classification of Diseases for Oncology. Gliomas were analysed separately to all brain cancers. Organ doses were reconstructed using historical machine settings and a large sample of CT images. Excess relative risks (ERRs) of brain cancer per 100 mGy of cumulative brain dose were calculated with linear dose-response modelling. The outcome was the first reported diagnosis of brain cancer after an exclusion period of 5 years after the first electronically recorded CT examination. FINDINGS: We identified 948 174 individuals, of whom 658 752 (69%) were eligible for our study. 368 721 (56%) of 658 752 participants were male and 290 031 (44%) were female. During a median follow-up of 5·6 years (IQR 2·4-10·1), 165 brain cancers occurred, including 121 (73%) gliomas. Mean cumulative brain dose, lagged by 5 years, was 47·4 mGy (SD 60·9) among all individuals and 76·0 mGy (100·1) among people with brain cancer. A significant linear dose-response relationship was observed for all brain cancers (ERR per 100 mGy 1·27 [95% CI 0·51-2·69]) and for gliomas separately (ERR per 100 mGy 1·11 [0·36-2·59]). Results were robust when the start of follow-up was delayed beyond 5 years and when participants with possibly previously unreported cancers were excluded. INTERPRETATION: The observed significant dose-response relationship between CT-related radiation exposure and brain cancer in this large, multicentre study with individual dose evaluation emphasises careful justification of paediatric CTs and use of doses as low as reasonably possible. FUNDING: EU FP7; Belgian Cancer Registry; La Ligue contre le Cancer, L'Institut National du Cancer, France; Ministry of Health, Labour and Welfare of Japan; German Federal Ministry of Education and Research; Worldwide Cancer Research; Dutch Cancer Society; Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat de Catalunya, Spain; US National Cancer Institute; UK National Institute for Health Research; Public Health England.

Incidence of cancer among Nordic police officers.

Police work may expose officers to various circumstances that have potential for increasing their risk of cancer, including traffic-related air pollution, night shift work and radiation from radars. In this study, we examined the incidence of cancer among Nordic male and female police officers. We utilize data from the Nordic Occupational Cancer (NOCCA) project, which linked census data on occupations from Finland, Iceland, Norway and Sweden to national cancer registries for the period 1961 to 2005. We report standardized incidence ratios (SIR) and 95% confidence intervals (CI) of selected cancers for each country by sex, age and calendar period. The cohort included 38 523 male and 1998 female police officers. As compared with the general population, male police officers had a 7% (95% CI: 4-9%) excess cancer risk, with elevated SIRs for various cancer sites, including prostate (SIR 1.19, 1.14-1.25), breast (SIR 1.77, 1.05-2.80), colon (SIR 1.22, 1.12-1.32) and skin melanoma (SIR 1.44, 1.28-1.60). Conversely, male police officers had a lower risk of lung cancer than the general population (SIR 0.72, 0.66-0.77). In female police officers, the SIR for cancer overall was 1.15 (0.98-1.34), and there was a slight excess of cancers of the breast (SIR 1.25, 0.97-1.59) and colon (SIR 1.21, 0.55-2.30). In conclusion, cancer incidence among the police officers was slightly higher than in the general population. Notably, SIRs were elevated for cancer sites potentially related to night shift work, namely colon, breast and prostate cancer.

Exposure to pesticides and risk of Hodgkin lymphoma in an international consortium of agricultural cohorts (AGRICOH).

PURPOSE: Some pesticides may increase the risk of certain lymphoid malignancies, but few studies have examined Hodgkin lymphoma (HL). In this exploratory study, we examined associations between agricultural use of 22 individual active ingredients and 13 chemical groups and HL incidence. METHODS: We used data from three agricultural cohorts participating in the AGRICOH consortium: the French Agriculture and Cancer Cohort (2005-2009), Cancer in the Norwegian Agricultural Population (1993-2011), and the US Agricultural Health Study (1993-2011). Lifetime pesticide use was estimated from crop-exposure matrices or self-report. Cohort-specific covariate-adjusted overall and age-specific (< 40 or ≥ 40 years) hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression and combined using random effects meta-analysis. RESULTS: Among 316 270 farmers (75% male) accumulating 3 574 815 person-years at risk, 91 incident cases of HL occurred. We did not observe statistically significant associations for any of the active ingredients or chemical groups studied. The highest risks of HL overall were observed for the pyrethroids deltamethrin (meta-HR = 1.86, 95% CI 0.76-4.52) and esfenvalerate (1.86, 0.78-4.43), and inverse associations of similar magnitude were observed for parathion and glyphosate. Risk of HL at ≥ 40 years of age was highest for ever-use of dicamba (2.04, 0.93-4.50) and lowest for glyphosate (0.46, 0.20-1.07). CONCLUSION: We report the largest prospective investigation of these associations. Nonetheless, low statistical power, a mixture of histological subtypes and a lack of information on tumour EBV status complicate the interpretability of the results. Most HL cases occurred at older ages, thus we could not explore associations with adolescent or young adult HL. Furthermore, estimates may be attenuated due to non-differential exposure misclassification. Future work should aim to extend follow-up and refine both exposure and outcome classification.

Occupational exposures of firefighting and urinary tract cancer risk among men in the Norwegian Fire Departments Cohort.

OBJECTIVES: Increased risks of bladder cancer and mesothelioma were the strongest evidence for the recent reclassification of firefighting as carcinogenic (Group 1) by the International Agency for Research on Cancer. Our study aim was to develop indicators for specific firefighting exposures and examine associations with urinary tract cancer (UTC), including bladder cancer. METHODS: We developed indicators for exposure from employment at a fire department or in firefighting jobs, to fire and smoke, and to diesel exhaust for men in the Norwegian Fire Departments Cohort (n=4250). Incident UTC cases were obtained from the Cancer Registry of Norway (1960-2021). Poisson regression was used to estimate incidence rate ratios (IRR) with cumulative exposures grouped into tertiles (reference: lowest exposed tertile) with 0-year, 10-year and 15-year lagging of exposures. RESULTS: During 125 090 person-years of follow-up, there were 76 cases of UTC. IRRs were mostly non-significantly increased in the middle tertile and at or below 1 in the highest tertile for total duration of employment, number of fires attended and fire exposure score with and without lags. In the middle tertile for diesel exhaust exposure, UTC risk was elevated over twofold with 10-year (IRR 2.27, 95% CI 1.22 to 4.20) and 15- year (2.21, 1.18 to 4.16) lags, and near 1 in the highest tertile. Findings for bladder cancer were similar to those for UTC. CONCLUSIONS: Dose-response associations between the exposure indicators and UTC were not observed. Future studies using the indicators with more cases are needed.

Early detection of prostate cancer in firefighters: a register-based study of prognostic factors and survival.

OBJECTIVES: To examine age at diagnosis, prognostic factors and survival of prostate cancer (PCa) in Norwegian firefighters and three other occupations undergoing occupational health check-ups, and comparing with PCa cases in the general population. METHODS: All PCa cases diagnosed in 1960-2017 were extracted from the Cancer Registry of Norway. Firefighters, military employees, pilots and police officers were identified through occupational data from Statistics Norway. Age at diagnosis, clinical stage, prostate-specific antigen (PSA), Gleason score, performance status and overall survival and PCa-specific survival in cases in these occupations were compared with cases in the general population. RESULTS: Firefighters were significantly younger at PCa diagnosis than cases in the general population in 1960-1993 (mean difference: 2.1 years) and 2007-2017 (mean difference: 4.3 years). At diagnosis, firefighters had significantly lower PSA values, Gleason scores and performance status scores than the general population. Firefighters diagnosed in 2007-2017 had lower risk of all-cause death than the general population (crude HR 0.71 (0.53-0.95)). No difference remained after adjusting for age at diagnosis (HR 1.03 (0.77-1.37)). Firefighters were older at diagnosis in 1994-2006 (mean difference: 3.0 years), but showed no other significant differences in age at diagnosis, PSA values, Gleason scores or performance status compared with military employees, pilots and police officers. CONCLUSIONS: Younger age and better prognostic factors at PCa diagnosis among firefighters and other occupations with requirements for health check-ups than cases in the general population may indicate an increased diagnostic intensity, likely contributing to elevated PCa incidence in such occupations.

Malignant lymphoma and occupational exposure to extremely low frequency magnetic fields and electrical shocks: a nested case-control study in a cohort of four Nordic countries.

BACKGROUND: Exposure to extremely low frequency magnetic fields (ELF-MFs) and electric shocks is a common occupational risk factor in many workplaces. Recent investigations have highlighted a possible association between such exposures and lymphoma risk. This study was carried out to further explore the association between occupational exposure to ELF-MFs and electric shocks and risk of lymphoma in a large Nordic census-based cohort. METHODS: We included cases of non-Hodgkin's lymphoma (NHL, n=68 978), chronic lymphocytic leukaemia (CLL, n=20 615) and multiple myeloma (MM, n=35 467) diagnosed between 1961 and 2005 in Finland, Iceland, Norway and Sweden. Cases were matched to five controls by year of birth, sex and country. Lifetime occupational ELF-MF and electric shock exposures were assigned to jobs reported in population censuses using job-exposure matrices. The risk of cancer was assessed based on cumulative exposure to ELF-MF and electric shocks. ORs with 95% CIs were estimated using logistic models adjusted for occupational co-exposures relevant to lymphomas. RESULTS: Less than 7% of the cases experienced high levels of ELF-MF. We observed no increased risks among workers exposed to high levels of ELF-MF for NHL (OR: 0.93; CI 0.90 to 0.97), CLL (OR: 0.98; CI 0.92 to 1.05) or MM (OR: 0.96; CI 0.90 to 1.01). CONCLUSION: Our results do not provide support for an association between occupational exposure to ELF-MFs and electric shocks and lymphoma risk.

Comparison of cancer incidence and mortality in the Norwegian Fire Departments Cohort, 1960-2018.

OBJECTIVES: Elevated risk of cancer at several sites has been reported among firefighters, although with mixed findings. The purpose of this study was to calculate standardised incidence ratios (SIRs) and standardised mortality ratios (SMRs) for cancer and compare them to assess whether use of the different measures could be a source of inconsistencies in findings. METHODS: The Norwegian Fire Departments Cohort, comprising 4295 male employees who worked at 15 fire departments across Norway, was linked to health outcome registries for the period 1960-2018. SIRs and SMRs were derived using national reference rates. RESULTS: Overall, we observed elevated incidence of colon cancer (SIR, 95% CI 1.27, 1.01 to 1.58), mesothelioma (2.59, 1.12 to 5.11), prostate cancer (1.18, 1.03 to 1.34) and all sites combined (1.15, 1.08 to 1.23). Smaller, non-significant elevations were found for mortality of colon cancer (SMR, 95% CI 1.20, 0.84 to 1.67) and mesothelioma (1.66, 0.34 to 4.86), while SMR for prostate cancer was at unity. Potential errors were observed in some of the mortality data, notably for mesothelioma cases. Among those who died of cancer, 3.7% (n=14) did not have a prior diagnosis of malignancy at the same site group. CONCLUSIONS: Assessment of incidence or mortality did not greatly influence the interpretation of results. The most prominent differences in SIR and SMR appeared to be due to inconsistencies between sites of cancer diagnosis and cause of death. The difference in SIR and SMR for prostate cancer suggested a detection bias from differential screening practices.

Parental occupational exposures in wood-related jobs and risk of testicular germ cell tumours in offspring in NORD-TEST a registry-based case-control study in Finland, Norway, and Sweden.

OBJECTIVE: We assessed the association between parental prenatal exposures in wood-related jobs and risk of testicular germ cell tumours (TGCT) in offspring. METHODS: NORD-TEST, a registry-based case-control study in Sweden, Finland and Norway, included 8112 TGCT cases diagnosed at ages 14-49 years between 1978 and 2012 with no history of prior cancer, and up to four controls matched to each case on year and country of birth. Parents of cases and controls were identified via linkages with the population registries and their occupational information was retrieved from censuses. The Nordic Occupational Cancer Study Job-Exposure Matrix was used to assign occupational exposures to each parent. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Maternal wood-related job was not associated with the risk of TGCT in offspring (OR 1.08, CI 0.55-2.14), while paternal wood-related job was associated with a decreased risk of TGCT in offspring (OR 0.85, CI 0.75-0.96). None of the specific wood-related jobs, such as upholsterers, sawyers, or construction carpenters, were significantly associated with a risk of TGCT. Only exception was observed in a sensitivity analysis which showed an increased risk in the small group of sons of fathers working as 'cabinetmakers and joiners' the year before conception (OR of 2.06, CI 1.00-4.25). CONCLUSION: This large-scale NORD-TEST analysis provided no evidence of an association between parental prenatal exposures in wood-related jobs and TGCT in sons.

Cancer incidence among musicians: 45 years of follow-up in four Nordic countries.

BACKGROUND: There are studies suggesting that participation in musical activities may protect from cancer. On the other hand, some musicians have a lifestyle that might increase the risk of cancer. The objective of this study was to assess the cancer pattern of musicians in four Nordic countries. MATERIAL AND METHODS: This study combines census and cancer registry data from 1961 to 2005 for 13 million people from Finland, Iceland, Norway, and Sweden. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for entire national populations used as reference rates. RESULTS: There were 11,401 male and 3105 female musicians with 2039 cancer cases. The SIR for all sites combined was 1.02 (95% confidence interval 0.97-1.07) in men and 1.04 (0.94-1.15) in women. In male musicians, there were statistically significant excesses in oropharyngeal cancer (4.36, 2.73-6.60), esophageal cancer (2.08, 1.51-2.81), liver cancer (1.81, 1.26-2.52), and skin melanoma (1.40, 1.10-1.75). The risk was decreased in lip cancer (0.13, 0.02-0.48), stomach cancer (0.66, 0.50-0.82), and lung cancer (0.77, 0.65-0.90). In female musicians, there were no statistically significant SIRs in any of the cancer types studied, but the risk of breast cancer was significantly elevated in the age category of 70+ (1.52, 1.04-2.15). The overall SIR was stable over the 45 year period of observation, but strong decreases were observed in the SIRs of esophageal cancer, liver cancer, laryngeal cancer, and skin melanoma. CONCLUSION: Musicians have characteristics of indoor workers such as low incidence of lip cancer and high incidence of skin melanoma. The low incidence of lung cancer suggests that the prevalence of smoking among musicians is lower than in the general population while the elevated risk of alcohol-related cancer types suggest that drinking is likely more common among musicians. The cancer risk for all sites combined is still similar to that of the general population in the four countries studied.

Occupational Noise Exposure and Vestibular Schwannoma: A Case-Control Study in Sweden.

It has been suggested that the association between self-reported occupational noise exposure and vestibular schwannoma (VS), found in several studies, represents recall bias. Therefore, we aimed to study the relationship in a large case-control study using occupational noise measurements. We performed a case-control study using data from Sweden for 1,913 VS cases diagnosed in 1961-2009 and 9,566 age- and sex-matched population controls. We defined occupational history by linkage to national censuses from 1960, 1970, 1980, and 1990. We estimated occupational noise exposure for each case and control using a job-exposure matrix. There was no association between occupational noise exposure and VS. Among subjects assessed as ever exposed to occupational noise levels of ≥85 dB (214 cases and 1,142 controls), the odds ratio for VS per 5 years of exposure was 1.02 (95% confidence interval: 0.90, 1.17). Workers with noise levels of ≥85 dB for at least 15 years (5-year latency period), showed no increased risk of VS (odds ratio = 0.98, 95% confidence interval: 0.73, 1.31) compared with those who had never been exposed to noise levels of 75 dB or higher. In summary, our large study does not support an association between occupational noise exposure and VS.

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix.

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

A genome-wide association study on medulloblastoma.

INTRODUCTION: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. METHODS: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. RESULTS: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10-5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10-8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10-4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10-3). CONCLUSION: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

Smoking-adjusted risk of kidney cancer by occupation: a population-based cohort study of Nordic men.

Background: Evidence suggests that among some occupational groups, there is an elevated risk of kidney cancer. This might, however, derive from a difference in smoking habits across occupational groups. The objective of this study was to determine smoking-adjusted occupational variation in the incidence of kidney cancer in Nordic males.Material and Methods: The source population for this study consisted of 7.4 million men from Denmark, Iceland, Finland, Norway, and Sweden. Data on occupation were obtained from national censuses conducted in the years 1960-1990. Data on cancer cases came from national cancer registries. A proxy for the occupation-specific smoking prevalence among all Nordic men was calculated based on the occupation-specific smoking prevalence and lung cancer incidence data for Finnish men. Smoking-adjusted standardized incidence ratio (SIRadj) with 95% confidence intervals (95%CI) were calculated for each occupational group.Results: The highest SIRadj estimates were observed in dentists (1.32, 95%CI 1.06-1.62), journalists (1.20, 95%CI 1.00-1.42), physicians (1.19, 95%CI 1.03-1.36), public safety workers (1.18, 95%CI 1.10-1.26), administrators (1.17, 95%CI 1.13-1.22), military personnel (1.16, 95%CI 1.05-1.28), and religious workers (1.17, 95%CI 1.09-1.26). The lowest SIRadj was observed among forestry workers (0.82, 95%CI 0.76-0.88).Conclusions: Tobacco smoking plays an important role in the occupational variation in the risk of kidney cancer. The smoking-adjusted incidence of kidney cancer was increased in dentists, physicians, journalists, administrators, and public safety workers.

The HARMONIC project: study design for the assessment of radiation doses and associated cancer risks following cardiac fluoroscopy in childhood.

The HARMONIC project (Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Paediatrics) is a European study aiming to improve our understanding of the long-term health risks from radiation exposures in childhood and early adulthood. Here, we present the study design for the cardiac fluoroscopy component of HARMONIC. A pooled cohort of approximately 100 000 patients who underwent cardiac fluoroscopy procedures in Belgium, France, Germany, Italy, Norway, Spain or the UK, while aged under 22 years, will be established from hospital records and/or insurance claims data. Doses to individual organs will be estimated from dose indicators recorded at the time of examination, using a lookup-table-based dosimetry system produced using Monte Carlo radiation transport simulations and anatomically realistic computational phantom models. Information on beam geometry and x-ray energy spectra will be obtained from a representative sample of radiation dose structured reports. Uncertainties in dose estimates will be modelled using 2D Monte Carlo methods. The cohort will be followed up using national registries and insurance records to determine vital status and cancer incidence. Information on organ transplantation (a major risk factor for cancer development in this patient group) and/or other conditions predisposing to cancer will be obtained from national or local registries and health insurance data, depending on country. The relationship between estimated radiation dose and cancer risk will be investigated using regression modelling. Results will improve information for patients and parents and aid clinicians in managing and implementing changes to reduce radiation risks without compromising medical benefits.

Cancer incidence and mortality among firefighters.

Firefighters are exposed to both known and suspected carcinogens. This study aims to systematically review the literature on the association of firefighting occupation and cancer incidence and mortality, overall and for specific cancer sites. A systematic review using PubMed, Embase, and Web of Science was performed up to January 1, 2018. We extracted risk estimates of cancers and calculated summary incidence risk estimates (SIRE), summary mortality risk estimates (SMRE), and their 95% confidence intervals (CI). Publication bias and risk of bias in individual studies were assessed using Begg's and Egger's tests and the Newcastle-Ottawa scale (NOS), respectively. We included 50 papers in the review and 48 in the meta-analysis. We found significantly elevated SIREs for cancer of the colon (1.14; CI 1.06 to 1.21), rectum (1.09; CI 1.00 to 1.20), prostate (1.15; CI 1.05 to 1.27), testis (1.34; CI 1.08 to 1.68), bladder (1.12; CI 1.04 to 1.21), thyroid (1.22; CI 1.01 to 1.48), pleura (1.60; CI 1.09 to 2.34), and for malignant melanoma (1.21; CI 1.02 to 1.45). We found significant SMREs of 1.36 (1.18 to 1.57) and 1.42 (1.05 to 1.90) for rectal cancer and Non-Hodgkin's lymphoma, respectively. Considering the significantly elevated risk of some cancers in this occupational group, we suggest improving preventive measures and securing adequate and relevant medical attention for this group. Further studies with more accurate and in-depth exposure assessments are indicated.

Describing mortality trends for major cancer sites in 133 intermediate regions of Brazil and an ecological study of its causes.

BACKGROUND: In Brazil, 211 thousand (16.14%) of all death certificates in 2016 identified cancer as the underlying cause of death, and it is expected that around 320 thousand will receive a cancer diagnosis in 2019. We aimed to describe trends of cancer mortality from 1996 to 2016, in 133 intermediate regions of Brazil, and to discuss macro-regional differences of trends by human development and healthcare provision. METHODS: This ecological study assessed georeferenced official data on population and mortality, health spending, and healthcare provision from Brazilian governmental agencies. The regional office of the United Nations Development Program provided data on the Human Development Index in Brazil. Deaths by misclassified or unspecified causes (garbage codes) were redistributed proportionally to known causes. Age-standardized mortality rates used the world population as reference. Prais-Winsten autoregression allowed calculating trends for each region, sex and cancer type. RESULTS: Trends were predominantly on the increase in the North and Northeast, whereas they were mainly decreasing or stationary in the South, Southeast, and Center-West. Also, the variation of trends within intermediate regions was more pronounced in the North and Northeast. Intermediate regions with higher human development, government health spending, and hospital beds had more favorable trends for all cancers and many specific cancer types. CONCLUSIONS: Patterns of cancer trends in the country reflect differences in human development and the provision of health resources across the regions. Increasing trends of cancer mortality in low-income Brazilian regions can overburden their already fragile health infrastructure. Improving the healthcare provision and reducing socioeconomic disparities can prevent increasing trends of mortality by all cancers and specific cancer types in Brazilian more impoverished regions.

Occupation and risk of cancer of the renal pelvis in Nordic countries.

OBJECTIVES: To evaluate occupational variation in the incidence of the malignant neoplasm of the renal pelvis in the population of the Nordic countries: Denmark, Iceland, Finland, Norway and Sweden. MATERIALS AND METHODS: The study cohort comprised 14.9 million individuals. Data on occupational history were obtained from national censuses. Standardized incidence ratios (SIRs) were calculated for each occupation. RESULTS: The highest SIRs were found in seamen (1.51, 95% confidence interval [CI] 1.23-1.82), printers (1.39, 95% CI 1.11-1.71), welders (1.37, 95% CI 1.03-1.78), and public safety workers (1.35, 95% CI 1.12-1.62). The lowest SIRs were observed in forestry workers (0.47, 95% CI 0.35-0.62), gardeners (0.72, 95% CI 0.62-0.83) and woodworkers (0.81, 95% CI 0.72-0.91). CONCLUSIONS: The study suggests that there is an association between profession and risk of malignancy of the renal pelvis. The possible associations between exposure to asbestos, heavy metals and welding fumes, and risk of developing the disease should be studied further.