Characterizations of uveal melanoma patients with three additional primary malignancies.

PURPOSE: In a population-based cohort of 960 uveal melanoma (UM) patients, we describe patients with three additional malignancies, including one unique patient with four synchronous primary malignancies. METHOD: A descriptive presentation of the clinical course and outcome for UM patients with three additional primary malignancies. RESULTS: After more than 20 years of follow-up of the UM cohort, 11 patients (1.1%) were diagnosed with three additional primary malignancies before, simultaneously or after UM. Among these, one patient had four synchronous primary malignancies, detected during workup for a symptomatic UM. All diagnoses were treated during the following 4 months, firstly the breast cancer, thereafter, the lung and pancreatic cancers and finally the UM. The patient died 3 years later of abdominal carcinomatosis due to the pancreatic cancer. The family history and gene testing did not disclose any genetic predisposition for cancer. A comparison of the four synchronous tumours, morphologically and immunohistochemically, showed no similarities and the expression of antibodies was different. CONCLUSION: Patients with UM may be diagnosed with non-ocular additional primary cancers. Thus, a comprehensive workup is obligatory and a further follow-up of the UM patients seems necessary. The UM is not always the main problem.

Clustering and trajectories of key noncommunicable disease risk factors in Norway: the NCDNOR project.

Noncommunicable diseases (NCDs) are a leading cause of premature death globally and have common preventable risk factors. In Norway, the NCDNOR-project aims at establishing new knowledge in the prevention of NCDs by combining information from national registries with data from population-based health studies. In the present study, we aimed to harmonize data on key NCD risk factors from the health studies, describe clustering of risk factors using intersection diagrams and latent class analysis, and identify long-term risk factor trajectories using latent class mixed models. The harmonized study sample consisted of 808,732 individuals (1,197,158 participations). Two-thirds were exposed to ≥ 1 NCD risk factor (daily smoking, physical inactivity, obesity, hypertension, hypercholesterolaemia or hypertriglyceridaemia). In individuals exposed to ≥ 2 risk factors (24%), we identified five distinct clusters, all characterized by fewer years of education and lower income compared to individuals exposed to < 2 risk factors. We identified distinct long-term trajectories of smoking intensity, leisure-time physical activity, body mass index, blood pressure, and blood lipids. Individuals in the trajectories tended to differ across sex, education, and body mass index. This provides important insights into the mechanisms by which NCD risk factors can occur and may help the development of interventions aimed at preventing NCDs.

Rates of Second Tumor, Metastasis, and Death From Cutaneous Squamous Cell Carcinoma in Patients With and Without Transplant-Associated Immunosuppression.

Importance: Cutaneous squamous cell carcinoma (cSCC) may occur with multiple primary tumors, metastasize, and cause death both in immunocompetent and immunosuppressed patients. Objective: To study the rates of second cSCC, metastasis, and death from cSCC in patients with and without organ transplant-associated immunosuppressive treatment. Design, Setting, and Participants: This population-based, nationwide cohort study used Cancer Registry of Norway data from 47 992 individuals diagnosed with cSCC at 18 years or older between January 1, 1968, and December 31, 2020. Data were analyzed between November 24, 2021, and November 15, 2022. Exposures: Receipt of a solid organ transplant at Oslo University Hospital between 1968 and 2012 followed by long-term immunosuppressive treatment. Main Outcomes and Measures: Absolute rates of second cSCC, metastasis, and death from cSCC were calculated per 1000 person-years with 95% CIs. Hazard ratios (HRs) estimated using Cox proportional hazard regression were adjusted for age, sex, and year of first cSCC diagnosis. Results: The study cohort comprised 1208 organ transplant recipients (OTRs) (median age, 66 years [range, 27-89 years]; 882 men [73.0%] and 326 women [27.0%]) and 46 784 non-OTRs (median age, 79 years [range, 18-106 years]; 25 406 men [54.3%] and 21 378 women [45.7%]). The rate of a second cSCC per 1000 person-years was 30.9 (95% CI, 30.2-31.6) in non-OTRs and 250.6 (95% CI, 232.2-270.1) in OTRs, with OTRs having a 4.3-fold increased rate in the adjusted analysis. The metastasis rate per 1000 person-years was 2.8 (95% CI, 2.6-3.0) in non-OTRs and 4.8 (95% CI, 3.4-6.7) in OTRs, with OTRs having a 1.5-fold increased rate in the adjusted analysis. A total of 30 451 deaths were observed, of which 29 895 (98.2%) were from causes other than cSCC. Death from cSCC was observed in 516 non-OTRs (1.1%) and 40 OTRs (3.3%). The rate of death from cSCC per 1000 person-years was 1.7 (95% CI, 1.5-1.8) in non-OTRs and 5.4 (95% CI, 3.9-7.4) in OTRs, with OTRs having a 5.5-fold increased rate in the adjusted analysis. Conclusions and Relevance: In this cohort study, OTRs with cSCC had significantly higher rates of second cSCC, metastasis, and death from cSCC than non-OTRs with cSCC, although most patients with cSCC in both groups died from causes other than cSCC. These findings are relevant for the planning of follow-up of patients with cSCC and for skin cancer services.

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.

Risk of total hip arthroplasty after elite sport: linking 3304 former world-class athletes with the Norwegian Arthroplasty Register.

OBJECTIVES: At present, there is no cure for osteoarthritis (OA), but severe hip joint degeneration can require total hip arthroplasty (THA). The literature on OA after elite sport is limited. We hypothesise that elite athletic activity increases the risk of receiving a THA later in life. METHODS: We linked a cohort of former Norwegian world-class athletes (1402 females and 1902 males, active 1936-2006) to the Norwegian Arthroplasty Register (THA performed 1987-2020). We used standardised incidence ratio (SIR), one-minus Kaplan-Meier and relative Cox regression (relative HR, RHR), with 95% CIs, and funnel plots at age 75, to assess THA risk for different sport disciplines, joint impact categories of sport disciplines and sex. The risk of THA for the corresponding general Norwegian population was used as reference. RESULTS: We found an overall increased risk for THA for the former elite athletes (SIR 2.11, 95% CI 1.82 to 2.40) at age 75 years, compared with the general population. THA risk at age 75 years was 11.6% for female athletes and 8.3% for male athletes. SIR was 1.90 (95% CI 1.49 to 2.31) for female and 2.28 (95% CI 1.87 to 2.70) for male athletes. Among males, high joint impact sport disciplines were associated with increased risk compared with low-impact sport disciplines (RHR 1.81, 95% CI 1.06 to 3.08, p=0.029). CONCLUSION: Having been an elite athlete was associated with a doubling of THA risk compared with the general population for both sexes. High joint impact sport disciplines were associated with subsequent THA for male athletes.

Statin Use and Skin Cancer Risk: A Prospective Cohort Study.

Epidemiological studies on statin use in relation to skin cancer risk are scarce and yielded conflicting results. We explored this association in Etude Epidémiologique auprès de femmes de l'Education Nationale, a prospective cohort of French women born in 1925-1950. Health and lifestyle data were self-reported biennially and matched with drug reimbursement data, allowing the identification of participants' statin use since 2004. Multivariable cause-specific hazards regression models adjusted for skin cancer risk factors estimated hazard ratios with 95% confidence intervals. Over 2004-2014, 455 cutaneous melanoma, 1,741 basal cell carcinoma, and 268 squamous cell carcinoma cases were ascertained among 62,473 women. Compared with never use, there were no associations between ever use of statins and melanoma (hazard ratio = 1.16, 95% confidence interval = 0.94-1.44) or squamous cell carcinoma (hazard ratio = 0.89, 95% confidence interval = 0.66-1.19) risks and a decrease in basal cell carcinoma risk with ever use of statins (hazard ratio = 0.89, 95% confidence interval = 0.79-0.996). We found no trend of increasing or decreasing risks with dose, duration of use, time since first use, or age at first use and no statistically significant effect modification by pigmentary traits or residential UVR exposure. Because of the limited number of studies evaluating the associations between the use of statins and the risks of melanoma, basal cell carcinoma, and squamous cell carcinoma, these findings would deserve further investigation in other settings.

The Oslo Ischaemia Study: cohort profile.

PURPOSE: The Oslo Ischaemia Study was designed to investigate the prevalence and predictors of silent coronary disease in Norwegian middle-aged men, specifically validating exercise electrocardiography (ECG) findings compared with angiography. The study has been important in investigating long-term predictors of cardiovascular morbidity and mortality, as well as investigating a broad spectrum of epidemiological and public health perspectives. PARTICIPANTS: In 1972-1975, 2014 healthy men, 40-59 years old, were enrolled in the study. Comprehensive clinical examination included an ECG-monitored exercise test at baseline and follow-ups. The cohort has been re-examined four times during 20 years. Linkage to health records and national health registries has ensured complete endpoint registration of morbidity until the end of 2006, and cancer and mortality until the end of 2017. FINDINGS TO DATE: The early study results provided new evidence, as many participants with a positive exercise ECG, but no chest pain ('silent ischaemia'), did not have significant coronary artery stenosis after all. Still, they were over-represented with coronary disease after years of follow-up. Furthermore, participants with the highest physical fitness had lower risk of cardiovascular disease, and the magnitude of blood pressure responses to moderate exercise was shown to influence the risk of cardiovascular disease and mortality. With time, follow-up data allowed the scope of research to expand into other fields of medicine, with the aim of investigating predictors and the importance of lifestyle and risk factors. FUTURE PLANS: Recently, the Oslo Ischaemia Study has been found worthy, as the first scientific study, to be preserved by The National Archives of Norway. All the study material will be digitised, free to use and accessible for all. In 2030, the Oslo Ischaemia Study will be linked to the Norwegian Cause of Death Registry to obtain complete follow-up to death. Thus, a broad spectrum of additional opportunities opens.

Fasting serum potassium and long-term mortality in healthy men.

BACKGROUND: Serum potassium levels have been positively associated with cardiovascular mortality, but little is known about the association with cancer mortality and death due to other causes. We examined whether serum levels of potassium were associated with long-term mortality in a healthy cohort. METHODS: Oslo Ischemia Study invited 2341 initially healthy men aged 40-59 years with no use of medication to a comprehensive health survey in 1972. Fasting serum level of potassium (mmol/L) was ascertained at baseline for 1989 men. We have complete follow-up for death throughout 2017. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and adjusted for multiple confounders. RESULTS: After a median follow-up of 30 years (interquartile range 21.2-38.7), 1736 deaths were observed, of which 494 were cancer deaths, 688 cardiovascular deaths, and 536 deaths related to other causes. Restricted cubic spline analysis showed that potassium level was linearly and positively associated with long-term cancer mortality; HR per mmol/L 1.8, 95% CI 1.4-2.4. Compared with low levels of potassium (≤ 4.0 mmol/L), men with high levels (≥4.6 mmol/L) showed a significantly 78% higher risk of cancer death. A positive linear association was found for all-cause mortality (HR per mmol/L 1.6, 95% CI 1.4-1.8), and for cardiovascular (HR per mmol/L 1.4, 95% CI 1.1-1.7) and other cause mortality (HR per mmol/L 1.7, 95% CI 1.3-2.2). CONCLUSIONS: These findings suggest that serum potassium level appears to predict long-term mortality in healthy middle-aged men, and it might imply future surveillance strategies for individuals with high serum potassium levels.

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.

Waiting times and treatment following cancer diagnosis: comparison between immigrants and the Norwegian host population.

Background: There are concerns about timely access to appropriate cancer treatment for the growing immigrant population in Norway. This study aims to compare waiting times between cancer diagnosis and start of cancer treatment, as well as treatment patterns between immigrants in Norway and the host population.Material and methods: We performed a nationwide, registry-based study with individual-level data, including 213,320 Norwegians and 8324 immigrants diagnosed with breast, colorectal, lung or prostate cancer in 1990-2014. Differences in time from diagnosis to treatment and in treatment patterns were described for the selected cancer sites. The Cox and logistic regressions were used to adjust for patient and tumour characteristics.Results: After adjustment for covariates, hazard ratios for time from diagnosis to treatment for non-Western immigrants compared to Norwegians were 0.88 (95% confidence interval (CI): 0.82-0.95) for breast cancer and 0.84 (95% CI: 0.75-0.95) for lung cancer, indicating longer waiting times. Treatment patterns in the four major cancer sites were similar among immigrants and the Norwegian host population, except for breast cancer, where women from East and South Asia received less breast-conserving surgery than the Norwegian host population (adjusted odds ratios 0.65 (95% CI: 0.46-0.93) for East Asians and 0.75 (95% CI: 0.50-1.13) for South Asians).Conclusions: The present study reports delayed treatment for lung and breast cancer among immigrants from non-Western countries in Norway. Systematic differences in cancer treatment were not detected. However, less breast-conserving surgery among breast cancer patients from Asia compared to Norwegians was observed.

Serum 25-hydroxyvitamin D levels predict cancer survival: a prospective cohort with measurements prior to and at the time of cancer diagnosis.

PURPOSE: Circulating 25-hydroxyvitamin D (25-OHD) levels have been inversely associated with cancer death, but the nature of this relationship is unclear. We investigated this association using repeated measurements of serum 25-OHD. PATIENTS AND METHODS: Pre-diagnostic serum samples were collected in population health surveys in Norway (1973-2004). Participants who subsequently developed cancer (1984-2004) provided a second serum sample at the time of cancer diagnosis. Samples were stored in the Janus Serum Bank. Repeated samples existed from 202 breast cancers, 193 lung cancers, 124 lymphomas, and 37 colon cancers. Serum 25-OHD was measured via competitive radioimmunoassay. Cox regression models assessed associations between 25-OHD and cancer-specific death (case fatality) through 2012, given as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The median time between pre-diagnostic and diagnostic samples was 14.4 years. The median 25-OHD levels were 63.3 and 62.5 nmol/L, respectively. During follow-up, 313 cancer deaths occurred. Compared to low pre-diagnostic 25-OHD levels (<46 nmol/L), higher levels (≥46 nmol/L) had significantly lower HRs (39-54%) of case fatality. This result was also seen for the diagnostic samples. Donors who had both samples at high (≥62 nmol/L) levels had 59% lower HR of case fatality, compared to those for whom both samples were at low levels (<46 nmol/L). Furthermore, versus a decline in serum 25-OHD (median -22.4 nmol/L) from pre-diagnostic to diagnostic samples, a rise (median 22.3 nmol/L) was associated with lower case fatality (HR 0.57, 95% CI 0.43-0.75). CONCLUSION: Our findings suggest a causal relationship between vitamin D and cancer case fatality.

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.

Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts.

BACKGROUND: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. METHODS: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. RESULTS: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. CONCLUSIONS: Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.

Quality assurance in melanoma care: The EU-MELACARE study.

BACKGROUND: A significant disparity regarding survival outcome for melanoma among European regions is well recognized and access to high quality care for European melanoma patients needs to be improved. There is an unmet need for the implementation of minimal standard of care within defined clinical pathways and Quality Assurance (QA) indicators. OBJECTIVE: The EU-MELACARE study aims to identify shared variables for cutaneous melanoma cases recorded in melanoma registries across Europe. MATERIAL AND METHODS: Opinion leaders involved in melanoma data registration and care quality analysis in 34 European countries were invited to respond to an expert survey covering questions regarding the melanoma registration practice in their countries and the characteristics, coverage and variables collected by the relevant melanoma registries. RESULTS: Data regarding 13 melanoma registries from 11 European countries contributed to the study. The majority (61,5%) were population based registries and more than half (62%) had national coverage. The included registries collected a median of 38 variables (Interquartile Range, IRQ 21-76). We identified 24 shared variables available in >70% of registries. CONCLUSIONS: This study provides valuable specific information on information recorded for melanoma cases are registered within Europe. A core of shared variables has been identified, which will constitute the basis for a standardized set of QA indicators for assessing and monitoring melanoma care across European countries.

Differences in cancer survival between immigrants in Norway and the host population.

Cancer survival is an important indicator for quality of cancer care. We sought to determine if there are differences in cancer survival between immigrants and the host population in Norway. We performed a nationwide registry-based study comprising subjects diagnosed with cancer between 1990 and 2014, and followed until the end of 2016. Survival was estimated for 13 cancer sites with cause-specific survival. Adjustments were made for common confounders (age, sex, year of diagnosis and place of residence) and defined mediators (stage at diagnosis, comorbidity and socioeconomic factors). A total of 500,255 subjects were available for analysis, of which 11,252 were Western and 8,701 non-Western immigrants. We did not find differences in cancer survival between Western immigrants and Norwegians, while non-Western immigrants, with some exceptions, had similar or better survival. Better lung cancer survival in non-Western immigrants than Norwegians was notable (hazard ratio (95% confidence interval): 0.78 (0.71-0.85)), and not explained by defined mediators. Immigrants from Eastern Europe and Balkan with melanoma (hazard ratio: 1.54 (1.12-2.12)) and prostate cancer (hazard ratio: 1.34 (1.08-1.67)), and possibly from sub-Saharan Africa with breast cancer (hazard ratio: 1.41 (0.94-2.12)) had worse survival than Norwegians. The results suggest that immigrants in Norway have good cancer survival relative to the host population. Poor survival in immigrants from Eastern Europe and Balkan with melanoma and prostate cancer, and sub-Saharan Africa with breast cancer might be a concern.

High mortality due to cutaneous melanoma in Norway: a study of prognostic factors in a nationwide cancer registry.

PURPOSE: The purpose of this study was to examine why Norway has the highest rate of mortality due to cutaneous melanoma (CM) in Europe. The Norwegian Malignant Melanoma Registry (NMMR) enables the study of clinical and histopathological characteristics of patients who die due to CM. RESULTS: The NMMR and the Norwegian Cause of Death Registry provided data on the clinical and histopathological factors as well as the date and cause of death, through June 2015 for all first invasive CMs diagnosed in 2008-2012 (n=8087). Cox regression was used to estimate associations between clinical and pathological factors and CM-specific death. Multiple imputation was used to handle missing data. RESULTS: The CMs were equally distributed between men (49.9%) and women (50.1%), and the median follow-up was 4.0 years (range: 0.08-7.5 years). Trunk was the most common anatomic site (48%), superficial spreading melanoma was the dominant melanoma subtype (68.2%), median Breslow thickness was 1.0 mm, ulceration was present in 23% of CMs, and 91.8% of cases were in a local clinical stage at diagnosis. Compared to women, men were diagnosed at a higher age, with thicker and more-often-ulcerated tumor, and more often were in advanced clinical stages. During follow-up, 1015 patients died due to CM, representing 52.8% of all deaths. The nodular subtype made up the dominant proportion of fatal CM cases (55.3% in women, 64.6% in men). Sex, age, anatomic site (trunk), T-stage, ulceration, clinical stage, and having a second primary CM were associated with increased risk of CM-specific death. CONCLUSION: Our data suggest that the high rate of mortality due to CM observed in Norway is attributable to the more advanced stage of the disease at diagnosis. Most high-risk cases occurred in male patients ≥70 years of age. Efforts to improve awareness and secondary prevention of CM, including warning signs of all melanoma subtypes, are required urgently and should be targeted toward men in particular.

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.