Benzene exposure and risk of lung cancer in the Norwegian Offshore Petroleum Worker cohort: a prospective case-cohort study.

OBJECTIVE: The objective of our study was to examine whether occupational exposure to benzene is associated with lung cancer among males in the Norwegian Offshore Petroleum Workers cohort. METHODS: Among 25 347 male offshore workers employed during 1965-1998, we conducted a case-cohort study with 399 lung cancer cases diagnosed between 1999 and 2021, and 2035 non-cases sampled randomly by 5-year birth cohorts. Individual work histories were coupled to study-specific job-exposure matrices for benzene and other known lung carcinogens. Weighted Cox regression was used to estimate HRs and 95% CIs for the associations between benzene exposure and lung cancer, by major histological subtypes, adjusted for age, smoking and occupational exposure to welding fumes, asbestos and crystalline silica. Missing data were imputed. RESULTS: For lung cancer (all subtypes combined), HRs (95% CIs) for the highest quartiles of benzene exposure versus unexposed were 1.15 (0.61 to 2.35) for cumulative exposure, 1.43 (0.76 to 2.69) for duration, and 1.22 (0.68 to 2.18) for average intensity (0.280≤P-trend≤0.741). For 152 adenocarcinoma cases, a positive trend was observed for exposure duration (P-trend=0.044). CONCLUSIONS: In this cohort of offshore petroleum workers generally exposed to low average levels of benzene, we did not find an overall clear support for an association with lung cancer (all subtypes combined), although an association was suggested for duration of benzene exposure and adenocarcinoma. The limited evidence might be due to restricted statistical power.

Injuries after violence and accidents - the forgotten pandemic? / Skader etter vold og ulykker ­ den glemte pandemi?

All information on injuries should be collected in a national injury registry devised for research. This will pave the way for a new strategy for injury prevention.

Night shift work, chemical coexposures and risk of female breast cancer in the Norwegian Offshore Petroleum Workers (NOPW) cohort: a prospectively recruited case-cohort study.

OBJECTIVES: This study examined the association between night shift work and risk of breast cancer, overall and by hormone receptor subtype, among females in the Norwegian Offshore Petroleum Workers (NOPW) cohort. We also examined the association of coexposure (chlorinated degreasers and benzene) and breast cancer risk, and possible interaction with work schedule. DESIGN: Prospectively recruited case-cohort study within the NOPW cohort. SETTING: Female offshore petroleum workers active on the Norwegian continental shelf. PARTICIPANTS: 600 female workers (86 cases and 514 non-cases) were included in the study. We excluded workers that died or emigrated before start of follow-up, had missing work history, were diagnosed with breast cancer or other prior malignancy (except non-melanoma skin cancer) before start of follow-up. RESULTS: No overall association was found between breast cancer risk and work schedule (HR 0.87, 95% CI 0.52 to 1.46 for work schedule involving night shift vs day shift only). There was no significant association between work schedule and risk of any breast cancer subtype. No significant interactions were found between work schedule and chemical coexposures (breast cancer overall Pinteraction chlorinated degreasers=0.725 and Pinteraction benzene=0.175). CONCLUSIONS: Our results did not provide supporting evidence that work schedule involving night shift affects breast cancer risk in female offshore petroleum workers, but should be considered cautiously due to few cases. Further studies with larger sample sizes are warranted.

Injury Prevention and long-term Outcomes following Trauma-the IPOT project: a protocol for prospective nationwide registry-based studies in Norway.

INTRODUCTION: Traumatic injuries constitute a major cause of mortality and morbidity. Still, the public health burden of trauma in Norway has not been characterised using nationwide registry data. More knowledge is warranted on trauma risk factors and the long-term outcomes following trauma. The Injury Prevention and long-term Outcomes following Trauma project will establish a comprehensive research database. The Norwegian National Trauma Registry (NTR) will be merged with several data sources to pursue the following three main research topics: (1) the public health burden of trauma to society (eg, excess mortality and disability-adjusted life-years (DALYs)), (2) trauma aetiology (eg, socioeconomic factors, comorbidity and drug use) and (3) trauma survivorship (eg, survival, drug use, use of welfare benefits, work ability, education and income). METHODS AND ANALYSIS: The NTR (n≈27 000 trauma patients, 2015-2018) will be coupled with the data from Statistics Norway, the Norwegian Patient Registry, the Cause of Death Registry, the Registry of Primary Health Care and the Norwegian Prescription Database. To quantify the public health burden, DALYs will be calculated from the NTR. To address trauma aetiology, we will conduct nested case-control studies with 10 trauma-free controls (drawn from the National Population Register) matched to each trauma case on birth year, sex and index date. Conditional logistic regression models will be used to estimate trauma risk according to relevant exposures. To address trauma survivorship, we will use cohort and matched cohort designs and time-to-event analyses to examine various post-trauma outcomes. ETHICS AND DISSEMINATION: The project is approved by the Regional Committee for Medical Research Ethics. The project's data protection impact assessment is approved by the data protection officer. Results will be disseminated to patients, in peer-reviewed journals, at conferences and in the media.

Use of Immunomodulating Drugs and Risk of Cutaneous Melanoma: A Nationwide Nested Case-Control Study.

PURPOSE: Cutaneous melanoma is among the fastest growing malignancies in Norway and ultraviolet radiation (UVR) exposure is the primary environmental risk factor. Immunomodulating drugs can increase skin photosensitivity and suppress immune responses, and by such mechanisms influence melanoma risk. We, therefore, aimed to examine the associations between use of immunomodulating drugs and melanoma risk, at a nationwide population level. PATIENTS AND METHODS: In the Cancer Registry of Norway, we identified all cases aged 18-85 with a first primary cutaneous melanoma diagnosed in 2007-2015 (n=12,106). These were matched to population controls from the Norwegian National Registry 1:10 (n=118,564), on sex and year of birth using risk set sampling. Information on prescribed drugs (2004-2015) was obtained by linkage to the Norwegian Prescription Database (NorPD). Conditional logistic regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for associations between use of immunomodulating drugs (immunosuppressants and corticosteroids) and melanoma risk, adjusted for ambient UVR and other drug use. RESULTS: Compared with ≤1 prescription, use of ≥8 prescriptions of immunosuppressants was associated with increased risk of melanoma (RR 1.50, 95% CI 1.27, 1.77). Similar associations were found for subgroups of immunosuppressants: drugs typically prescribed to organ transplant recipients (OTRs) (RR 2.02, 95% CI 1.35, 3.03) and methotrexate (RR 1.27, 95% CI 1.04, 1.55). Similar results were found for high levels of cumulative doses and across all histological subtypes. Use of corticosteroids was not associated with melanoma risk. CONCLUSION: We found a positive association between use of immunosuppressants and melanoma risk, with the highest risk seen for drugs prescribed to OTRs. Knowledge about this risk increase is important for physicians and users of these drugs, for intensified surveillance, awareness and cautious sun exposure.

Harmonizing work history data in epidemiologic studies with overlapping employment records.

BACKGROUND: Work history data often require major data management including handling of overlapping jobs to avoid overestimating exposure before linkage to job-exposure matrices (JEMs) is possible. METHODS: In a case-cohort study of 1825 male Norwegian offshore petroleum workers, 3979 jobs were reported (mean duration 2417 days/job; maximum 8 jobs/worker). Each job was assigned to one of 27 occupation categories. Overlapping jobs of the same category (1142 jobs) were collapsed and overlapping jobs of different categories (1013 jobs) were split. The resulting durations were weighted by a factor accounting for the number of overlapping jobs. RESULTS: Collapsing overlapping jobs within the same category resulted in 3295 jobs (mean 2629 days/job). Splitting overlapping jobs of different categories increased the number to 4239 jobs (mean 2043 days/job), while the total duration in days dropped by 10%. CONCLUSIONS: We demonstrated that overlapping employment data structures can be harmonized in a systematic and unbiased way, preparing work history data for linkage to several JEMs.

Cardiovascular, antidepressant and immunosuppressive drug use in relation to risk of cutaneous melanoma: a protocol for a prospective case-control study.

INTRODUCTION: The incidence of cutaneous melanoma (hereafter melanoma) has increased dramatically among fair-skinned populations worldwide. In Norway, melanoma is the most rapidly growing type of cancer, with a 47% increase among women and 57% among men in 2000-2016. Intermittent ultraviolet exposure early in life and phenotypic characteristics like a fair complexion, freckles and nevi are established risk factors, yet the aetiology of melanoma is multifactorial. Certain prescription drugs may have carcinogenic side effects on the risk of melanoma. Some cardiovascular, antidepressant and immunosuppressive drugs can influence certain biological processes that modulate photosensitivity and immunoregulation. We aim to study whether these drugs are related to melanoma risk. METHODS AND ANALYSIS: A population-based matched case-control study will be conducted using nation-wide registry data. Cases will consist of all first primary, histologically verified melanoma cases diagnosed between 2007 and 2015 identified in the Cancer Registry of Norway (14 000 cases). Ten melanoma-free controls per case (on date of case melanoma diagnosis) will be matched based on sex and year of birth from the National Registry of Norway. For the period 2004-2015, and by using the unique personal identification numbers assigned to all Norwegian citizens, the case-control data set will be linked to the Norwegian Prescription Database for information on drugs dispensed prior to the melanoma diagnosis, and to the Medical Birth Registry of Norway for data regarding the number of child births. Conditional logistic regression will be used to estimate associations between drug use and melanoma risk, taking potential confounding factors into account. ETHICS AND DISSEMINATION: The project is approved by the Regional Committee for Medical Research Ethics in Norway and by the Norwegian Data Protection Authority. The study is funded by the Southeastern Norway Regional Health Authority. Results will be published in peer-reviewed journals and disseminated further through scientific conferences, news media and relevant patient interest groups.

Vitamin D, obesity and leptin in relation to bladder cancer incidence and survival: prospective protocol study.

INTRODUCTION: Bladder cancer (BC) (including renal pelvis, ureter and urethra) is one of the most common urogenital cancers and the fourth most frequent cancer in men in the USA. In Norway, the incidence of BC has increased over the last decades. The age-standardised incidence rates per 100 000 for 2011-2015 were 53.7 in men and 16.5 in women. Compared to the 5-year period 2006-2010, the percentage increase in incidence was 6.1% in men and 12.3% in women. The recurrence rate of BC is over 50%, the highest recurrence rate of any malignancy. Smoking and occupational exposure to aromatic amines are recognised as the major risk factors. Recently, low-serum level of 25-hydroxy vitamin D (25(OH)D) and obesity have been suggested to increase the BC risk, and leptin, which is important in weight regulation, may be involved in bladder carcinogenesis. More knowledge on potential risk factors for BC is necessary for planning and implementing primary prevention measures. METHODS AND ANALYSES: Cohort and nested case-control studies will be carried out using the population-based Janus Serum Bank Cohort consisting of prediagnostic sera, clinical measurement data (body height and weight, body surface area and weight change over time, blood pressure, cholesterol and triglycerides) and self-reported information on lifestyle factors (smoking, physical activity). Participants were followed from cohort inclusion (1972-2003) through 2014. The cohort will be linked to the Cancer Registry of Norway (cancer data), the National Cause of Death Registry (date and cause of death), National Population Registry (vital status) and Statistic Norway (education and occupation). Serum samples will be analysed for 25(OH)D, vitamin D binding protein, leptin, albumin, calcium and parathyroid hormone. Cox regression and conditional logistic regression models and mediation analysis will be used to estimate association between the exposures and BC. ETHICS AND DISSEMINATION: The study has been approved by the Regional Committee for Medical Research Ethics and is funded by the Norwegian Cancer Society. Results will be published in peer-reviewed journals, at scientific conferences and through press releases.

Aromatic hydrocarbons and risk of skin cancer by anatomical site in 25 000 male offshore petroleum workers.

BACKGROUND: We prospectively examined skin cancer risk according to occupational exposure to aromatic hydrocarbons with adjustment for ultraviolet radiation exposure, in a cohort of 24 917 male offshore petroleum workers. METHODS: Hazard ratios (HRs) and 95% confidence intervals were estimated with Cox regression adapted to a stratified case-cohort design. RESULTS: During 13.5 years of follow-up, 112 cutaneous melanomas (CMs) and 70 non-melanoma skin cancers were identified. Increased risks of CM and of squamous cell carcinoma on the forearm and hand were seen among those ever exposed to crude oil or benzene. For skin cancers of the forearm and hand combined, cumulative and duration metrics of benzene exposure showed Ptrends of 0.031 and 0.003, respectively. CONCLUSIONS: Our results support an association between exposure to crude oil or benzene and skin cancer risk on hands and forearms among offshore petroleum workers. Dermal uptake of polycyclic aromatic hydrocarbons or benzene may explain this association.

A protocol for prospective studies of 25-hydroxyvitamin D, leptin and body mass index in relation to cutaneous melanoma incidence and survival.

INTRODUCTION: The incidence and mortality rates of cutaneous melanoma (CM) are increasing among fair-skinned populations worldwide. Ultraviolet radiation (UVR) is the principal risk factor for CM, but is also the main source of 25-hydroxyvitamin D (25(OH)D), which has been associated with reduced risk and better prognosis of some cancer types. However, both low and high 25(OH)D levels have been associated with increased risk of CM. Obesity as measured by body mass index (BMI) is associated with risk of several cancers and has also been suggested as a risk factor for CM, and may also be related to insufficient 25(OH)D and/or high leptin levels. Moreover, contracting a CM diagnosis has been associated with increased risk of developing second cancer. We aim to study whether low prediagnostic serum levels of 25(OH)D, high prediagnostic levels of BMI and high serum leptin levels influence CM incidence, Breslow thickness and CM mortality, and risk of second cancer and survival after a CM diagnosis. METHODS AND ANALYSIS: Cohort and nested case-control studies will be carried out using the population-based Janus Serum Bank Cohort (archival prediagnostic sera, BMI, smoking and physical activity), with follow-up from 1972 to 2014. Additional data will be received from the Cancer Registry of Norway, the national Cause of Death Registry, Statistics Norway (education and occupation) and exposure matrices of UVR. Time-to-event regression models will be used to analyse the cohort data, while the nested case-control studies will be analysed by conditional logistic regression. A multilevel approach will be applied when incorporating group-level data. ETHICS AND DISSEMINATION: The project is approved by the Regional Committee for Medical Research Ethics and is funded by the Norwegian Cancer Society. Results will be published in peer-reviewed journals, at scientific conferences and in the news media.