Leon Alexander Mclaren Berge

• Heibati, Behzad; Soursou, Georgia; Abimbola, Samuel; Charisiadis, Pantelis; Eleftheriou, Lygia & Berge, Leon Alexander Mclaren [Show all 8 contributors for this article] (2025). BTEX chrono-metabolism and leukemogenic effects of night shift work in workers of gasoline stations: the EXPOSOWORK prospective panel study in Bulgaria. Journal of the National Cancer Center. 5(5), p. 546–546. doi: 10.1016/j.jncc.2025.01.006. Full text in Research Archive
• Shala, Nita Kaupang; Veierød, Marit Bragelien; Babigumira, Ronnie; Berge, Leon Alexander Mclaren; Samuelsen, Sven Ove & Kirkeleit, Jorunn [Show all 14 contributors for this article] (2025). Occupational exposures and kidney cancer among 25 000 male offshore petroleum industry workers: relative risks and healthy worker survivor bias. American Journal of Epidemiology. ISSN 0002-9262. 195(1), p. 81–91. doi: 10.1093/aje/kwaf039. Full text in Research Archive Show summary

  Kidney cancer has been a suspected occupational disease in petroleum workers. Health conditions that are linked to kidney cancer may prompt termination or change of work, and thereby restrict occupational exposures in high-risk individuals, creating a healthy worker survivor bias (HWSB). We examined associations between occupational exposures and kidney cancer among males in the Norwegian Offshore Petroleum Workers (NOPW) cohort using a case-cohort design, with 169 incident cancers identified by linkage to national registry data (1999-2021) and a subcohort of 2090 non-cases, all employed 1965-1998. Relative risks (hazard ratios, HRs) by cumulative exposure to benzene, crude oil, chlorinated degreasing agents (CDA), asbestos, welding fumes, or surface treatment (priming, painting), were estimated by weighted Cox regression. Inverse exposure-response trends suggested HWSB, reinforced by analyses of necessary components of HWSB. Bias was partly alleviated by adjustment for total employment duration, and by 20-year lagging of cumulative exposure to benzene, crude oil, or CDA. Workers in surface treatment (ever vs. never) showed increased HR=2.22, 95% confidence interval 1.04-4.72 (9 cases, only). For asbestos and welding fumes, the initial inverse trends largely remained after adjustment. In sum, we could neither confirm nor exclude an occupational impact on kidney cancer.

• Babigumira, Ronnie; Veierød, Marit Bragelien; Larsen, Inger Kristin; Berge, Leon Alexander Mclaren; Shala, Nita Kaupang & Marjerrison, Niki [Show all 22 contributors for this article] (2025). Benzene exposure and risk of colorectal cancer by anatomical subsite in the Norwegian offshore petroleum workers cohort. Environmental Research. ISSN 0013-9351. 276, p. 1–9. doi: 10.1016/j.envres.2025.121407. Full text in Research Archive Show summary

  Objective: To investigate the association between low levels of benzene exposure (≤0.879 parts per million [ppm]-years) and risk of colorectal cancer (CRC) including its anatomical subsites. Methods: Among 25,347 male workers in the Norwegian Offshore Petroleum Workers (NOPW) cohort with offshore work history (1965–1998), 455 CRC cases were diagnosed 1999–2021. We compared these with a subcohort (n = 2031) drawn from the full cohort. Work histories were linked to a previously developed industry-specific benzene job-exposure matrix (JEM). Cox regression for case-cohort analyses was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC, adjusted for age, body mass index, smoking, alcohol intake, red/processed meat intake, and physical activity. Results: Risks of CRC increased with increasing benzene exposure. For all CRC, the HRs (95% CI) for the most exposed [quartile 4] vs. the unexposed were 1.32 (0.96 to 1.81, [0.177–0.879 ppm-years]; p-trend = 0.085) for cumulative, 1.52 (1.11 to 2.07, [17–34 years]; p-trend = 0.032) for duration, and 1.56 (1.15 to 2.12, [0.015–0.046 ppm]; p-trend = 0.005) for average intensity of benzene exposure. For right-sided colon cancer, the association was most evident for exposure duration (HR = 2.25 (1.33 to 3.80), quartile 4 [17–34 years] vs. unexposed; p-trend = 0.007). Sensitivity analyses showed consistent associations. Conclusion: This study found positive exposure-response associations between low-level benzene exposure and CRC risk in offshore petroleum workers. These findings add to emerging evidence that benzene can be associated with solid tumours including lung and bladder, which potentially has important occupational and public health implications.

• Berge, Leon Alexander Mclaren; Shala, Nita Kaupang; Barone-Adesi, Francesco; Hosgood, H Dean; Samuelsen, Sven Ove & Bråtveit, Magne [Show all 13 contributors for this article] (2024). Exposure to fibres and risk of pleural mesothelioma in the Norwegian Offshore Petroleum Workers cohort. Occupational and Environmental Medicine. ISSN 1351-0711. 81(7), p. 331–338. doi: 10.1136/oemed-2024-109424. Full text in Research Archive Show summary

  Objectives Pleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure to asbestos or refractory ceramic fibres (RCFs) and pleural mesothelioma among male Norwegian offshore petroleum workers. Methods Among 25 347 men in the Norwegian Offshore Petroleum Workers (NOPW) cohort (1965–1998), 43 pleural mesothelioma cases were identified through the Cancer Registry of Norway (1999–2022). A case–cohort study was conducted with 2095 randomly drawn non-cases from the cohort. Asbestos and RCF exposures were assessed with expert-made job-exposure matrices (JEMs). Weighted Cox regression was used to estimate HRs and 95% CIs, adjusted for age at baseline and pre-offshore employment with likely asbestos exposure. Results An increased risk of pleural mesothelioma was indicated for the highest versus lowest tertile of average intensity of asbestos (HR=1.21, 95% CI: 0.57 to

• Ghiasvand, Reza; Berge, Leon Alexander Mclaren; Kulle, Bettina; Green, Adele C.; Rahmoun, Marie Al & Fournier, Agnès [Show all 9 contributors for this article] (2023). Statin use and risk of cutaneous melanoma: a nationwide nested case-control study. British Journal of Dermatology. ISSN 0007-0963. 188(6), p. 805–807. doi: 10.1093/bjd/ljad057. Full text in Research Archive Show summary

  This nationwide nested case–control study examined the association between statin use and risk of cutaneous melanoma. We included 12 048 adult patients with melanoma and 117 895 randomly selected cancer-free controls, matched on age and sex. Cancer data were obtained from the Cancer Registry of Norway and data on drug use was retrieved from the Norwegian Prescription Database. We estimated rate ratios with 95% confidence intervals and conducted sensitivity analyses. We observed an inverse dose–response association between statin use and melanoma risk, stronger in women. The highest statin intake was associated with a reduced risk of melanoma, particularly on the head/neck and lower limbs. Our finding may have implications for melanoma prevention in high-risk groups.

• Shala, Nita Kaupang; Stenehjem, Jo; Babigumira, Ronnie; Liu, Fei-Chih; Berge, Leon Alexander Mclaren & Silverman, Debra T. [Show all 16 contributors for this article] (2023). Exposure to benzene and other hydrocarbons and risk of bladder cancer among male offshore petroleum workers. British Journal of Cancer. ISSN 0007-0920. 129(5), p. 838–851. doi: 10.1038/s41416-023-02357-0. Full text in Research Archive Show summary

  Background Occupational exposures constitute the second leading cause of urinary bladder cancer after tobacco smoking. Increased risks have been found in the petroleum industry, but high-quality exposure data are needed to explain these observations. Methods Using a prospective case-cohort design, we analysed 189 bladder cancer cases (1999–2017) and 2065 randomly drawn non-cases from the Norwegian Offshore Petroleum Workers cohort. Cases were identified in the Cancer Registry of Norway, while work histories (1965–1998) and lifestyle factors were recorded by questionnaire at baseline (1998). Occupational petroleum-related hydrocarbon exposures were assessed by expert-developed job-exposure matrices. Hazard ratios were estimated by weighted Cox-regressions, adjusted for age, tobacco smoking, education, and year of first employment, and with lagged exposures. Results Increased risks were found in benzene-exposed workers, either long-term exposure (≥18.8 years, HR = 1.89, 95% CI: 1.14–3.13; p-trend = 0.044) or high-level cumulative benzene exposure (HR = 1.60, 95% CI: 0.97–2.63; p-trend = 0.065), compared with the unexposed. Associations persisted with 20-year exposure lag. No associations were found with skin or inhalation exposure to crude oil, mineral oil (lubrication, hydraulics, turbines, drilling), or diesel exhaust. Conclusions The results suggest that exposures in the benzene fraction of the petroleum stream may be associated with increased bladder cancer risk.

• Berge, Leon Alexander Mclaren; Liu, Fei-Chih; Grimsrud, Tom Kristian; Babigumira, Ronnie; Støer, Nathalie Charlotte & Kjærheim, Kristina [Show all 15 contributors for this article] (2022). Night shift work and risk of aggressive prostate cancer in the Norwegian Offshore Petroleum Workers (NOPW) cohort. International Journal of Epidemiology. ISSN 0300-5771. 52(4), p. 1003–1014. doi: 10.1093/ije/dyac235. Full text in Research Archive Show summary

  Background: Night shift work may acutely disrupt the circadian rhythm, with possible carcinogenic effects. Prostate cancer has few established risk factors though night shift work, a probable human carcinogen, may increase the risk. We aimed to study the association between night shift work and chlorinated degreasing agents (CDAs) as possible endocrine disrupters in relation to aggressive prostate cancer as verified malignancies. Methods: We conducted a case-cohort study on 299 aggressive prostate cancer cases and 2056 randomly drawn non-cases in the Norwegian Offshore Petroleum Workers cohort (1965-98) with linkage to the Cancer Registry of Norway (1953-2019). Work history was recorded as years with day, night, and rollover (rotating) shift work, and CDA exposure was assessed with expert-made job-exposure matrices. Weighted Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for aggressive prostate cancer, adjusted for education and year of first employment, stratified by 10-year birth cohorts, and with 10, 15, and 20 years of exposure lag periods. Results: Compared with day work only, an increased hazard of aggressive prostate cancer (HR = 1.86, 95% CI 1.18-2.91; P-trend = 0.046) was found in workers exposed to ≥19.5 years of rollover shift work. This persisted with longer lag periods (HR = 1.90, 95% CI 0.92-3.95; P-trend = 0.007). The exposure-hazard curve for a non-linear model increased linearly (HRs ≥1.00) for 18-26 years of rollover shift work. No association was found with CDA exposure. Conclusions: Long-term exposure to rollover shift work may increase the hazard of aggressive prostate cancer in offshore petroleum workers.

• Ghiasvand, Reza; Berge, Leon Alexander Mclaren; Kulle, Bettina; Stenehjem, Jo Steinson; Heir, Trond & Karlstad, Øystein [Show all 11 contributors for this article] (2022). Use of antihypertensive drugs and risk of cutaneous melanoma: A nationwide nested case-control study. International Journal of Epidemiology. ISSN 0300-5771. 52(3), p. 887–898. doi: 10.1093/ije/dyac223. Full text in Research Archive Show summary

  Abstract Background Most antihypertensives can induce dermal photosensitivity, which may increase melanoma risk. However, corroborating evidence is limited. We examined the associations between use of antihypertensives and melanoma risk. Methods A nationwide nested case-control study was conducted using data from the Cancer Registry of Norway, the National Registry and the Norwegian Prescription Database in 2004–15. Ten controls were randomly selected for each melanoma case, matched on sex and birth year. The study included 12 048 cases and 117 895 controls. We estimated rate ratios (RRs) with 95% confidence intervals (CIs). All analyses were adjusted for ambient ultraviolet radiation (UVR). We additionally performed active comparator analyses, and sensitivity analyses by only including new users, distinguishing between exclusive and mixed users, allowing for different latency periods, and subgroup analyses by melanoma subtype and clinical stage. Results Compared with non-use, we observed a slightly increased melanoma risk in users of diuretics (RR 1.08, CI 1.01–1.15), calcium-channel blockers (RR 1.10, CI 1.04–1.18) and drugs affecting the renin-angiotensin system (RR 1.10, CI 1.04–1.16), but not for beta blockers (RR 0.97, CI 0.92–1.03). We found no heterogeneity of associations by melanoma subtype or clinical stage and no dose-response relationship between the cumulative defined daily doses (DDDs) and melanoma. No interaction was found between cumulative DDDs and ambient UVR. Conclusions Weak associations, with lack of a dose-response relationship and lack of interactions with ambient UVR, in the DDD analysis in this nationwide study do not support a causal relationship between antihypertensives and melanoma risk.

• Berge, Leon Alexander Mclaren; Grimsrud, Tom Kristian; Babigumira, Ronnie; Støer, Nathalie Charlotte; Shala, Nita Kaupang & Veierød, Marit Bragelien [Show all 7 contributors for this article] (2022). Cancer epidemiology in practice: Working notes on cancer history-based selection and censoring. Norsk Epidemiologi. ISSN 0803-2491. 30(1-2), p. 107–112. doi: 10.5324/nje.v30i1-2.4986. Full text in Research Archive Show summary

  Researchers conducting observational studies of exposure-cancer associations must make decisions regarding the selection and censoring of study subjects with respect to their cancer history. Given available information, this may include cancers prior to start of follow-up (prevalent cases), and multiple primary cancers (MPCs) at the same or different time-points during follow-up. The choice of analytical strategy may have implications for statistical power and for potential biases. We discuss herein two approaches, the “all cancer approach” and the “first primary cancer approach”. Each contains a set of criteria, primarily for, but not limited to, cohort studies of exposure-cancer associations. Both approaches exclude subjects with prevalent cancers at start of follow-up to avoid information and selection bias but differ in terms of case definition and censoring criteria. In the “all cancer approach”, subjects are censored on non-eligible cancer subtypes of the cancer under study, though subjects with MPCs are not censored on other incident cancers preceding or occurring simultaneously (at time of diagnosis) with the cancer under study. To limit the influence of prior treatment regimens, the “first primary cancer approach” censors subjects upon any first primary incident cancer not under study, including any “simultaneous” MPCs, as well as non-eligible subtypes of the cancer under study. Depending on the cancer under study, these approaches may yield different estimates of the exposure-cancer association and may in this regard be utilized for sensitivity analyses. These alternative approaches are presented and discussed here as a potential resource and source of further discussion for peers in the field of cancer epidemiology.

• Berge, Leon Alexander; Kulle, Bettina; Stenehjem, Jo S.; Heir, Trond; Furu, Kari & Juzeniene, Asta [Show all 11 contributors for this article] (2020). Use of Antidepressants and Risk of Cutaneous Melanoma: A Prospective Registry-Based Case-Control Study. Clinical Epidemiology. 12, p. 193–202. doi: 10.2147/CLEP.S241249. Full text in Research Archive Show summary

  Purpose: Melanoma is the cancer with the most rapidly rising incidence rate in Norway. Although exposure to ultraviolet radiation (UVR) is the major environmental risk factor, other factors may also contribute. Antidepressants have cancer inhibiting and promoting side effects, and their prescription rates have increased in parallel with melanoma incidence. Thus, we aimed to prospectively examine the association between use of antidepressants and melanoma by using nation-wide data from the Cancer Registry of Norway, the National Registry, the Norwegian Prescription Database and the Medical Birth Registry of Norway. Patient and Methods: All cases aged 18– 85 with a primary cutaneous invasive melanoma diagnosed during 2007– 2015 (n=12,099) were matched to population controls 1:10 (n=118,467) by sex and year of birth using risk-set sampling. We obtained information on prescribed antidepressants and other potentially confounding drug use (2004– 2015). Conditional logistic regression was used to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs) for the association between overall and class-specific use of antidepressants and incident melanoma. Results: Compared with ≤ 1 prescription, ≥ 8 prescriptions of antidepressants overall were negatively associated with melanoma (RR 0.81 CI 0.75– 0.87). Class-specific analyses showed decreased RRs for selective serotonin reuptake inhibitors (RR 0.82 CI 0.73– 0.93) and mixed antidepressants (RR 0.77 CI 0.69– 0.86). The negative association was found for both sexes, age ≥ 50 years, residential regions with medium and highest ambient UVR exposure, all histological subtypes, trunk, upper and lower limb sites and local disease. Conclusion: Use of antidepressants was associated with decreased risk of melanoma. There are at least two possible explanations for our results; cancer-inhibiting actions induced by the drug and less UVR exposure among the most frequent users of antidepressants.

• Robsahm, Trude Eid; Stenehjem, Jo S.; Berge, Leon Alexander & Veierød, Marit Bragelien (2020). Prevalence of Indoor Tanning Among Teenagers in Norway Before and After Enforcement of Ban for Ages Under 18 Years. Acta Dermato-Venereologica. ISSN 0001-5555. 100(8). doi: 10.2340/00015555-3482. Full text in Research Archive
• Berge, Leon Alexander; Kulle, Bettina; Stenehjem, Jo S.; Heir, Trond; Karlstad, Øystein & Juzeniene, Asta [Show all 11 contributors for this article] (2020). Use of immunomodulating drugs and risk of cutaneous melanoma: A nationwide nested case-control study. Clinical Epidemiology. 12, p. 1389–1401. doi: 10.2147/CLEP.S269446. Full text in Research Archive Show summary

  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.

• Berge, Leon Alexander; Kulle, Bettina; Stenehjem, Jo S.; Larsen, Inger Kristin; Furu, Kari & Juzeniene, Asta [Show all 11 contributors for this article] (2019). Cardiovascular, antidepressant and immunosuppressive drug use in relation to risk of cutaneous melanoma: A protocol for a prospective case-control study. BMJ Open. 9:e025246(2), p. 1–8. doi: 10.1136/bmjopen-2018-025246. Full text in Research Archive Show summary

  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 analysisA 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 disseminationThe 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.

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• Perrier, Flavie; Rimal, Raju; Green, Adele C; Rueegg, Corina Silvia; Ghiasvand, Reza & Gjersvik, Petter [Show all 13 contributors for this article] (2026). Breslow thickness and melanoma-specific death in patients diagnosed with thin cutaneous melanoma in 1983-2019. Full text in Research Archive
• Liu, Fei-Chih; Veierød, Marit Bragelien; Kjærheim, Kristina; Robsahm, Trude Eid; Ghiasvand, Reza & Babigumira, Ronnie [Show all 11 contributors for this article] (2021). Excess risk of male breast cancer in the Norwegian Offshore Petroleum Workers (NOPW) cohort: a possible link to extreme night shift work? Breast Cancer Research. ISSN 1465-5411. doi: 10.1186/s13058-021-01485-w. Full text in Research Archive

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