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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.

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.

Flavie Perrier,1 Reza Ghiasvand,2,3 Simon Lergenmuller,1 Trude E Robsahm,3 Adele C Green,4,5 Kristin B Borch,6 Torkjel M Sandanger,6 Elisabete Weiderpass,7 Corina S Rueegg,2 Marit B Veierød1 1Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; 2Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway; 3Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; 4QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 5Cancer Research UK Manchester and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; 6Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway; 7International Agency for Research on Cancer, Lyon, FranceCorrespondence: Flavie Perrier, Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, PO Box 1122, Blindern, Oslo, N-0317, Norway, Email flavie.perrier@medisin.uio.noPurpose: Physical activity (PA) is a cornerstone in disease prevention and varies throughout life. A pooled analysis of cohort studies and a meta-analysis of cohort studies found positive associations between PA and melanoma risk. However, previous studies focused on PA at specific ages and often lacked information on ultraviolet radiation (UVR) exposure. Using the population-based Norwegian Women and Cancer (NOWAC) cohort, including information on PA and UVR exposure, we estimated life-course PA trajectories from adolescence to adulthood and their associations with melanoma.Methods: Total PA across different domains (recreation, occupation, transport, household) was reported for ages 14 and 30 years, and when responding to the questionnaire (31– 76 years) using a 10-point scale, validated to rank PA levels in Norwegian females. We estimated life-course PA trajectories using a latent class mixed model in 152,248 women divided into three subcohorts depending on age at questionnaire completion: 31– 39 (n = 27,098), 40– 49 (n = 52,515) and ≥ 50 years (n = 72,635). The unique 11-digit identity number of Norwegian citizens was used to link NOWAC to the Cancer Registry of Norway for information on cancer diagnoses, emigration and death. Associations between PA trajectories and melanoma risk were estimated in each subcohort using multivariable Cox regression.Results: Five classes of individual life-course PA trajectories were identified in subcohort 31– 39 years (low, moderate, high, decreasing, increasing PA) and four in subcohorts 40– 49 and ≥ 50 years (low, moderate, high, decreasing PA). No significant association was found between life-course PA trajectories and melanoma risk in any subcohort. Hazard ratios (95% confidence intervals) for the high versus moderate trajectory were 0.92 (0.66– 1.29), 1.15 (0.97– 1.37) and 0.90 (0.78– 1.05) for subcohorts 31– 39, 40– 49 and ≥ 50 years, respectively.Conclusion: Our results do not support a positive association between PA and melanoma risk found in previous studies, which is important for public health guidelines promoting regular PA.Keywords: physical activity, cutaneous melanoma, trajectory, cohort, women, Norway

ObjectivesTo 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.MethodsAll 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.ResultsFirefighters 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.ConclusionsYounger 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.

Background and aims Statins are becoming more widely used among women of reproductive age; however, nationwide data on statin use across pregnancy is scarce. We therefore aimed to describe the drug utilization patterns for statins and other lipid-modifying agents (LMAs) before, during, and after pregnancy, for all pregnancies in Norway from 2005 to 2018. Methods We linked individual-level data from four nationwide electronic health care registries in Norway and characterized the prescription fills of statins and other LMAs across pregnancy. We also examined trends in pregnancy-related LMA use, and characterized women using statins and other LMAs on parameters of health status and co-morbidity. Results In total, 822,071 pregnancies for 503,723 women were included. The number of statin prescription fills decreased rapidly during the first trimester and returned to pre-pregnancy levels about one year postpartum. Pregnancy-related statin use increased from 2005 (approx. 0.11% of all pregnancies) to 2018 (approx. 0.29% of all pregnancies); however, in total, few statin prescriptions were filled within any trimester of pregnancy (n = 331, 0.04% of all pregnancies). Statin use was more common in women with higher age, higher weight, smoking, and comorbidities such as hypertension and diabetes mellitus; also, statin users often had co-medication pertinent to these conditions. Conclusions Although statins and other LMAs were increasingly being used around the time of pregnancy among women in Norway, drug use was mostly discontinued during the first trimester. Our results suggest that pregnancy-related statin use should be monitored, and that drug safety analyses for maternal and offspring health outcomes are needed.

Background More than one third of Norwegian women and men between 20 and 40 years of age have elevated cholesterol concentration. Parental metabolic health around conception or during pregnancy may affect the offspring’s cardiovascular disease risk. Lipids are important for fetal development, but the determinants of cord blood lipids have scarcely been studied. We therefore aimed to describe the associations between maternal and paternal peri-pregnancy lipid and metabolic profile and newborn cord blood lipid and metabolic profile. Methods This study is based on 710 mother–father–newborn trios from the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). The sample included in this study consisted of parents with and without self-reported hypercholesterolemia the last 6 months before pregnancy and their partners and newborns. Sixty-four cord blood metabolites detected by nuclear magnetic resonance spectroscopy were analyzed by linear mixed model analyses. The false discovery rate procedure was used to correct for multiple testing. Results Among mothers with hypercholesterolemia, maternal and newborn plasma high-density lipoprotein cholesterol, apolipoprotein A1, linoleic acid, docosahexaenoic acid, alanine, glutamine, isoleucine, leucine, valine, creatinine, and particle concentration of medium high-density lipoprotein were significantly positively associated (0.001 ≤ q ≤ 0.09). Among mothers without hypercholesterolemia, maternal and newborn linoleic acid, valine, tyrosine, citrate, creatinine, high-density lipoprotein size, and particle concentration of small high-density lipoprotein were significantly positively associated (0.02 ≤ q ≤ 0.08). Among fathers with hypercholesterolemia, paternal and newborn ratio of apolipoprotein B to apolipoprotein A1 were significantly positively associated (q = 0.04). Among fathers without hypercholesterolemia, no significant associations were found between paternal and newborn metabolites. Sex differences were found for many cord blood lipids. Conclusions Maternal and paternal metabolites and newborn sex were associated with several cord blood metabolites. This may potentially affect the offspring’s long-term cardiovascular disease risk.

Background Increased risk of cutaneous melanoma and squamous cell carcinoma (SCC) has been reported among petroleum workers, but few studies include females, exposure data on ultraviolet radiation (UVR), and potential confounding factors. We aimed to examine UVR exposure in relation to risk of melanoma and SCC among male and female offshore petroleum workers. We also examined the association between UVR exposure and melanoma (Breslow) thickness. Methods The Norwegian Offshore Petroleum Workers (NOPW) cohort (n = 27,917) holds information on sunbathing, indoor tanning, sunburns, sunscreen use, and other lifestyle factors recorded in 1998. Linkage to the Cancer Registry of Norway gave information on cancer diagnosis through 2017. We used Cox and logistic regression to estimate hazard ratios (HRs) of skin cancer and odds ratios (OR) of thick (≥1 mm) melanomas, respectively, with 95% confidence intervals (CIs). Results Melanoma risk increased with increasing frequency of sunbathing after age 20 (ptrend = 0.031), sunburn average intensity (ptrend = 0.028), and sunscreen use (HR = 2.16; 95% CI: 1.42 -3.27 for almost always vs. never/rarely). The risk of thick melanoma was inversely associated with sunbathing frequency after age 20 (OR = 0.38; 95% CI: 0.16 - 0.90 for ≥4 weeks/year vs. 1 week/year). SCC risk increased with increasing frequency of indoor tanning after age 20 (HR = 2.72; 95% CI: 1.22 - 6.05 for ≥3 times/months vs. never), sunburn average intensity (ptrend

Background Meta-analyses have shown firefighters to be at an increased risk of several cancer types. Occupational carcinogen exposure may explain these increased risks. This study aims to describe Norwegian fire departments' work conditions from 1950 until today, focusing on factors relevant for potential occupational carcinogen exposure. Methods With the help of a reference group, we developed a questionnaire on topics related to occupational exposure to carcinogens for the period 1950–2018. Selected Norwegian fire departments provided department-specific responses. Results Sixteen departments, providing fire services for 48% of the Norwegian population as of 2019 and mainly consisting of professional firefighters, responded to our questionnaire. The introduction of synthetic firefighting foams, more regular live fire training, the introduction of chemical diving, and a higher number of diesel-driven fire service vehicles were identified as changes thought to increase exposure to occupational carcinogens. Changes thought to decrease exposure included the switch from negative to positive pressure self-contained breathing apparatuses, the use of self-contained breathing apparatuses during all phases of firefighting, the use of ventilating fans during firefighting, increased attention to flammable materials used during live fire training, increased attention to handling and cleaning of turnout gear and other equipment, and installment of exhaust removal systems in apparatus bays. Conclusion Norwegian fire departments' work conditions have seen several changes since 1950, and this could influence firefighters' occupational carcinogen exposure. A peak of carcinogen exposure may have occurred in the 1970s and 1980s before recent changes have reduced exposure.

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.

Objectives“True” breast cancers, defined as not being visible on prior screening mammograms, are expected to be more aggressive than “missed” cancers, which are visible in retrospect. However, the evidence to support this hypothesis is limited. We compared the risk of death from any cause for women with true, minimal signs, and missed invasive screen-detected (SDC) and interval breast cancers (IC).MethodsThis nation-wide study included 1022 SDC and 788 IC diagnosed through BreastScreen Norway during 2005–2016. Cancers were classified as true, minimal signs, or missed by five breast radiologists in a consensus-based informed review of prior screening and diagnostic images. We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of death from any cause associated with true, minimal signs, and missed breast cancers, adjusting for age at diagnosis, histopathologic tumour diameter and grade, and subtype. Separate models were created for SDC and IC.ResultsAmong SDC, 463 (44%) were classified as true and 242 (23%) as missed; among IC, 325 (39%) were classified as true and 235 (32%) missed. Missed SDC were associated with a similar risk of death as true SDC (HR = 1.20, 95% CI (0.49, 2.46)). Similar results were observed for missed versus true IC (HR = 1.31, 95% CI (0.77, 2.23)).ConclusionsWe did not observe a statistical difference in the risk of death for women diagnosed with true or missed SDC or IC; however, the number of cases reviewed and follow-up time limited the precision of our estimates.Key Points• An informed radiological review classified screen-detected and interval cancers as true, minimal signs, or missed based on prior screening and diagnostic mammograms.• It has been hypothesised that true cancers, not visible on the prior screening examination, may be more aggressive than missed cancers.• We did not observe a statistical difference in the risk of death from any cause for women with missed versus true screen-detected or interval breast cancers.

Previous studies of serum 25-hydroxyvitamin D (25(OH)D) in relation to melanoma have shown conflicting results. We conducted a nested case–control study of 708 cases and 708 controls, using prediagnostically collected serum, to study 25(OH)D and melanoma risk in the population-based Janus Serum Bank Cohort. Stratified Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for ultraviolet radiation (UVR) indicators and stratified by ambient UVB of residence and body mass index (BMI). Non-linear associations were studied by restricted cubic splines. Missing data were handled with multiple imputation by chained equations. We found an HR of melanoma risk of 1.01 (95% CI: 0.99, 1.04) and an HRimputed of 1.02 (95% CI: 1.00, 1.04) per 5-nmol/L increase. The spline model showed exposure-risk curves with significantly reduced melanoma risk between 60 and 85 nmol/L 25(OH)D (reference 50 nmol/L). Non-significant J-shaped curves were found in sub-analyses of subjects with high ambient UVB of residence and of subjects with BMI 2. Our data did not yield persuasive evidence for an association between 25(OH)D and melanoma risk overall. Serum levels within the medium range might be associated with reduced risk, an association possibly mediated by BMI.

ObjectivesElevated 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.MethodsThe 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.ResultsOverall, 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.ConclusionsAssessment 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.

Background Ultraviolet radiation (UVR) exposure is a leading cause of skin cancers and an ubiquitous environmental exposure. However, the molecular mechanisms relating UVR exposure to melanoma is not fully understood. We aimed to investigate if lifetime UVR exposure influences DNA methylation, and if individual CpG sites could be robustly associated with UVR exposures.Methods We assessed DNA methylation in whole blood in three data sets (N = 183, 191, and 125) from the Norwegian Women and Cancer cohort, using Illumina methylation platforms (450k & EPIC). We studied genome-wide DNA methylation, targeted analyses of CpG sites indicated in the literature, global methylation (average over all CpGs and imputation of LINE-1 specific CpGs), and accelerated aging. Lifetime history of UVR exposure (residential ambient UVR, sunburns, sunbathing vacations and indoor tanning) was collected by questionnaires. Cumulative UVR exposure was calculated by adding sunbathing vacations and indoor tanning. We used one data set for discovery and the other two for replication. Results One CpG site showed a genome-wide significant association between cumulative UVR exposure and DNA methylation (cg01884057) (pnominal=3.96e-08), but was not replicated in any of the two replication sets (pnominal≥0.42). Four CpG sites (cg05860019, cg00033666, cg18984282, cg25792367) showed suggestive associations with the other UVR exposures. Conclusion We performed extensive analyses of the association between long-term UVR exposure and DNA methylation in lymphocytes. There was no indication of a robust effect of past UVR exposure on DNA methylation, and our results do not suggest mediation of UVR effects on melanoma risk by DNA methylation.

Objectives Firefighters are exposed to a variety of known and suspected carcinogens through their work. However, the association with cancer risk has limited evidence. We examined cancer incidence among firefighters in the newly established Norwegian Fire Departments Cohort restricted to sites with established associations with carcinogens encountered during firefighting. This included sites within the respiratory, urinary, and lympho-hematopoietic systems, and the skin and all sites combined. Methods Male firefighters (N=3881) in the cohort were linked to the Cancer Registry of Norway for incident cancer cases occurring during the period 1960–2018. We calculated standardized incidence ratios (SIR) with rates for the national male population as reference, and stratified SIR analyses by period of first employment, duration of employment, and time since first employment. Results Elevated risk was seen for all sites combined (SIR 1.15, 95% confidence interval 1.07–1.23). Elevated risk of urinary tract cancer was observed among firefighters who began working before 1950, and with observation ≥40 years since first employment. Risk of mesothelioma and laryngeal cancer were elevated with ≥40 years since first employment and with ≥30 years employment duration. Conclusions The observed associations between firefighting and urinary tract cancer, laryngeal cancer, and mesothelioma have been observed in some studies previously, and our results suggest the observed elevated risks are related to carcinogenic occupational exposures. Differences in risk by period of employment potentially reflect changes in exposures from improved quality and use of personal protective equipment.

BackgroundStatins are becoming more widely used among women of reproductive age; however, nationwide data on statin use across pregnancy is scarce. We therefore aimed to describe the drug utilization patterns for statins and other lipid-modifying agents (LMAs) before, during, and after pregnancy, for all pregnancies in Norway from 2005 to 2018.MethodsWe linked individual-level data from four nationwide electronic health care registries in Norway and characterized the prescription fills of statins and other LMAs across pregnancy. We also examined trends in pregnancy-related LMA use, and characterized women using statins and other LMAs on parameters of health status and co-morbidity.ResultsIn total 822 071 pregnancies for 503 723 women were included. The number of statin prescription fills decreased rapidly during first trimester and returned to pre-pregnancy levels about one year postpartum. Pregnancy-related statin use increased from 2005 (approx. 0.11 % of all pregnancies) to 2018 (approx. 0.29 % of all pregnancies); however, in total, few statin prescriptions were filled within any trimester of pregnancy (n = 331, 0.04 % of all pregnancies). Statin use was more common in women with higher age, higher weight, smoking, and comorbidities such as hypertension and diabetes mellitus; also, statin users often had co-medication pertinent to these conditions.ConclusionsAlthough statins and other LMAs were increasingly being used around the time of pregnancy among women in Norway, drug use was mostly discontinued during first trimester. Our results suggest that pregnancy-related statin use should be monitored, and that drug safety analyses for maternal and offspring health outcomes are needed.

Knowledge about factors associated with melanoma thickness, the most important prognostic factor for localized primary melanoma survival,1 may help reduce the risk of melanoma deaths. Previously reported associations of melanoma thickness with pigmentary characteristics, number of naevi, diet quality and body mass index (BMI)2–4 may be explained by behavioural and biological mechanisms. Physical activity (PA) has been associated with improved outcomes for several cancers,5 but its relation with melanoma thickness and prognosis is unknown.

Background - Breast cancer risk remains higher in high-income compared with low-income countries. However, it is unclear to what degree metabolic factors influence breast cancer development in women 30 years after immigration from low- to a high-incidence country. Methods - Using Cox regression models, we studied the association between pre-diagnostic metabolic factors and breast cancer development, and whether this association varied by ethnicity among 13,802 women participating in the population-based Oslo Ethnic Breast Cancer Study. Ethnic background was assessed and pre-diagnostic metabolic factors (body mass index, waist:hip ratio, serum lipids and blood pressure) were measured. A total of 557 women developed invasive breast cancer, and these women were followed for an additional 7.7 years. Results - Among women with an unfavorable metabolic profile, women from south Asia, compared with western European women, had a 2.3 times higher breast cancer risk (HR 2.30, 95% CI 1.18–4.49). Compared with the western European women, the ethnic minority women were more likely to present with triple-negative breast cancer (TNBC) (OR 2.11, 95% CI 0.97–4.61), and less likely to complete all courses of planned taxane treatment (OR 0.26, 95% CI 0.08–0.82). Among TNBC women, above-median triglycerides:HDL-cholesterol (>0.73) levels, compared with below-median triglycerides:HDL-cholesterol (≤0.73) levels, was associated with 2.9 times higher overall mortality (HR 2.88, 95% CI 1.02–8.11). Conclusions - Our results support the importance of metabolic factors when balancing breast cancer prevention and disease management among all women, and in particular among non-western women migrating from a breast cancer low-incidence to a high-incidence country.

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.