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.

Hospital surgical volume and colorectal cancer survival in Norway: A nationwide cohort study.

BACKGROUND: Studies of hospital surgical volume and colorectal cancer survival are inconclusive. We investigated whether surgical volume was associated with survival of patients operated for colorectal cancer in Norway. METHODS: Using Cancer Registry of Norway data, we compared excess mortality from colorectal cancer by hospital surgical volume among 26,989 colon and 9779 rectal cancer patients diagnosed 2009-2020 and followed-up to 31.12.2021. Hospitals were divided into terciles according to their three-year average annual surgical volume; colon: low (< 22), middle (22-73), high (> 73); rectal: low (< 17), middle (17-38), high (> 38). We estimated excess hazard ratios (EHR) with flexible parametric models adjusted for age, year, stage, surgical urgency and surgery location (within/outside patient's residential health trust). RESULTS: Low-volume hospitals had the highest proportion of late-stage or acutely operated colon cancer patients. Colon cancer patients operated at low- versus high-volume hospitals had significantly increased crude excess mortality (EHR = 1.30; 95 % CI = 1.14-1.48) but no difference after adjustment for age, year, and stage (EHR = 0.97; 0.85-1.11). High-volume hospitals had the highest proportion of late-stage rectal cancer patients and patients operated outside their residential area. Rectal cancer patients operated at low- versus high-volume hospitals did not have significantly different excess mortality before (EHR = 0.84; 0.64-1.10) or after (EHR = 1.03; 0.79-1.35) adjustment for age, year, stage, surgical urgency and surgery location. After accounting for case-mix, hospital surgical volume was not associated with excess mortality from colon (P = 0.40) or rectal cancer (P = 0.22). CONCLUSION: Low hospital surgical volume was not associated with poorer colorectal cancer survival.

Characteristics and fate of patients with rectal cancer not entering a curative-intent treatment pathway: A complete nationwide registry cohort of 3,304 patients.

BACKGROUND: Treatment options for advanced and metastatic rectal cancer have increased during the past decades. However, a considerable proportion of the patients are not eligible for curative treatment, and data on this subset are scarce from a population-based perspective. This study aimed to describe treatment pathways and survival in a national cohort of patients with primary stage IV rectal cancer or stage I-III rectal cancer not eligible for curative treatment. METHODS: A national cohort of all patients reported 2008-2015 to the Norwegian Colorectal Cancer Registry with primary metastatic rectal cancer or who did not undergo curative resections for stage I-III rectal cancer was studied with regard to patient characteristics, treatments, and survival. RESULTS: Of 8291 patients diagnosed with rectal cancer, 3304 (39.9%) were eligible for analysis. The majority (76.8%) had metastatic disease, and 23.2% did not undergo curative resections for other reasons. We identified four main treatment journeys: no tumour-directed treatment, 25.1%; resection of the primary tumour, 44.6%; oncological treatment, 28.4%; and R0 resection of the primary tumour and metastases, 1.9%; these translated into ten different treatment pathways. Survival differed considerably between a median of 5.3 months for M1 disease with non-tumour-directed treatment to a five-year survival of 67% for M1 with R0 resection. CONCLUSION: Almost 40% of all patients with rectal cancer did not enter a curative-intent treatment pathway. The patient journeys and outcomes varied greatly. This large but understudied population warrants further in-depth analyses of treatment efficacy and effects on quality of life.

Survival Trends of Right- and Left-Sided Colon Cancer across Four Decades: A Norwegian Population-Based Study.

BACKGROUND: Patients with right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ clinically and molecularly. The main objective was to investigate stage-stratified survival and recurrence of RCC and LCC across four 10-year periods. METHODS: Patients diagnosed from 1977 to 2016 with colon adenocarcinoma were included from the Cancer Registry of Norway. Primary tumor location (PTL) was defined as RCC if proximal and LCC if distal to the splenic flexure. Multivariable regressions were used to estimate HRs for overall survival (OS), recurrence-free survival (RFS), survival after recurrence (SAR), and excess HRs (eHR) for relative survival (RS). RESULTS: 72,224 patients were eligible for analyses [55.1% (n = 39,769/72,224) had RCC]. In 1977 to 1986, there was no difference between LCC and RCC in OS [HR, 1.01; 95% confidence interval (CI), 0.97-1.06; P = 0.581] or RS (eHR, 0.96; 95% CI, 0.90-1.02; P = 0.179). In 2007 to 2016, LCC had significantly better OS (HR, 0.84; 95% CI, 0.80-0.87; P < 0.001) and RS (eHR, 0.76; 95% CI, 0.72-0.81; P < 0.001) compared with RCC. The gradually diverging and significantly favorable prognosis for LCC was evident for distant disease across all time periods and for regional disease from 2007 onward. There was no difference in RFS between LCC and RCC in patients less than 75 years during 2007 to 2016 (HR, 0.99; 95% CI, 0.91-1.08; P = 0.819); however, SAR was significantly better for LCC (HR, 0.61; 95% CI, 0.53-0.71; P < 0.001). CONCLUSIONS: A gradually diverging and increasingly favorable prognosis was observed for patients with LCC with advanced disease over the past four decades. IMPACT: Current PTL survival disparities stress the need for further exploring targetable molecular subgroups across and within different PTLs to further improve patient outcomes.

The validity of cancer information on death certificates in Norway and the impact of death certificate initiated cases on cancer incidence and survival.

BACKGROUND: Death certificates are an important source of information for cancer registries. The aim of this study was to validate the cancer information on death certificates, and to investigate the effect of including death certificate initiated (DCI) cases in the Cancer Registry of Norway when estimating cancer incidence and survival. METHODS: All deaths in Norway in the period 2011-2015 with cancer mentioned on the death certificates were linked to the cancer registry. Notifications not registered from other sources were labelled death certificate notifications (DCNs), and considered as either cancer or not, based on available information in the registry or from trace-back to another source. RESULTS: From the total of 65 091 cancers mentioned on death certificates in the period 2011-2015, 58,425 (89.8%) were already in the registry. Of the remaining 6 666 notifications, 2 636 (2 129 with cancer as underlying cause) were not regarded to be new cancers, which constitutes 4.0% of all cancers mentioned on death certificates and 39.5% of the DCNs. Inclusion of the DCI cases increased the incidence of all cancers combined by 2.6%, with largest differences for cancers with poorer prognosis and for older age groups. Without validation, including the 2 129 disregarded death certificates would over-estimate the incidence by 1.3%. Including DCI cases decreased the five-year relative survival estimate for all cancer sites combined with 0.5% points. CONCLUSION: In this study, almost 40% of the DCNs were regarded not to be a new cancer case, indicating unreliability of death certificate information for cancers that are not already registered from other sources. The majority of the DCNs where, however, registered as new cases that would have been missed without death certificates. Both including and excluding the DCI cases will potentially bias the survival estimates, but in different directions. This biases were shown to be small in the Cancer Registry of Norway.

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.

Underlying conditions in adults with COVID-19. / Underliggende tilstander hos voksne med covid-19.

BACKGROUND: Cardiovascular diseases, cancer, type-2 diabetes and chronic obstructive pulmonary disease (COPD) were initially noted as the most common diseases among individuals who were hospitalised for COVID-19. However, the evidence base is weak. The objective of this study is to describe how selected diseases were distributed among adults with confirmed COVID-19 (COVID-19 positive tests) and among those hospitalised for COVID-19 compared to the general population. MATERIAL AND METHOD: We used data from the Norwegian Patient Registry, the Norwegian Registry for Primary Health Care and the Norwegian Surveillance System for Communicable Diseases for adults from the age of 20 and older for the period 1 March 2020-13 May 2020. RESULTS: Of all those who tested positive for COVID-19, 7 632 (94 %) were aged 20 years or older, and 1 025 (13.4 %) of these had been hospitalised. Among those hospitalised with COVID-19, there was a higher proportion of individuals with cardiovascular diseases (18.3 % versus 15.6 %), cancer (6.9 % versus 5.4 %), type-2 diabetes (8.6 % versus 5.2 %) and COPD (3.8 % versus 2.7 %) than in the general population as a whole after adjusting for age. The proportion of hospitalised patients with asthma, other chronic respiratory disease, cardiovascular disease, ongoing cancer treatment, complications related to hypertension, obesity and overweight, neurological disorders and cardiac and renal failure was also higher than in the general population. There were few differences between persons who had tested positive for COVID-19 and the general population in terms of underlying conditions. INTERPRETATION: Among those hospitalised for COVID-19, there was a higher proportion of patients with underlying illnesses than in the general population. This may indicate that these patients tend to have a more severe course of disease or that they are more likely to be hospitalised compared to healthy individuals. The results must be interpreted with caution, since the sample of COVID-19 individuals is non-random.

Education, income and risk of cancer: results from a Norwegian registry-based study.

INTRODUCTION: Several studies have shown an association between socioeconomic status and incidence of cancer. In this study, we have examined the association between socioeconomic factors, using income and education as proxies, and cancer incidence in Norway, a country known to be egalitarian, with universal access to health care and scoring high on the human development index. METHODS: We linked individual data for the total Norwegian population with information on all cancer patients registered in the Cancer Registry of Norway (CRN) with any cancer diagnosed between 2012 and 2016. Data on education, and individual income, were provided from Statistics Norway. We used Poisson regression to obtain incidence rate ratios (IRR) across education and income levels for 23 cancer sites. RESULTS: A total of 9 cancers among men and 13 cancers among women were observed to have significantly higher incidence rates in cases with the lowest level of education. Melanoma for both sexes, testis and prostate cancer in men, and breast cancer in women were found to have a higher incidence rate among those with the highest level of education. The largest differences in IRR were found for lung cancer, where men and women with college or university education as their highest completed education had a two- to threefold decreased risk, compared to those with primary school (IRR men; 0.40 [0.37-0.43], women 0.34 [0.31-0.37]). The results for income mirrored the results for education among men, while for women we did not observe many differences in cancer risk across income groups. CONCLUSION: Our findings were consistent with findings from other studies showing that the incidence rate of cancer differs across levels of socioeconomic status. We may need behavioral change campaigns focused on lifestyle changes that lower the risk of cancer and target perhaps to those with lower socioeconomic status.

Validation of Assisted Reproductive Technology in the Medical Birth Registry of Norway Versus the Norwegian Prescription Database.

BACKGROUND: Increasing attention has been given to the long-term effects of assisted reproductive technology (ART). This study assessed the validity and completeness of ART as registered in the Medical Birth Registry of Norway (MBRN) using drug prescription data from the Norwegian Prescription Database (NorPD) as reference. METHODS: In this nationwide registry validation study, we included all pregnancies recorded in the MBRN between 2005 and 2017. We estimated sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the MBRN, using data from the NorPD as reference. We obtained the total percentage of ART pregnancies that could be identified (completeness) from both registries using the capture-recapture method. We analyzed subgroups by maternal age, gestational length, mode of ART treatment, health region, and mode of registration of ART (ART institution or birth notification form). RESULTS: Twenty-three thousand seven hundred eighteen of a total 765,789 pregnancies were registered as ART pregnancies through the MBRN and 20,807 as ART pregnancies through the NorPD. The sensitivity of the MBRN was 85.1% (95% confidence interval [CI] = 84.7, 85.6) and the PPV was 74.7% (74.1-75.2). Sensitivity declined with increasing maternal age: 71.5% (69.4-73.7) in the age group 40-44 years, and 40.7% (22.2-59.3) in the ages above 45 years. Completeness when combining data was 96.2% (96.0-96.5). CONCLUSIONS: Our analysis shows that, when identifying women pregnant through ART, NorPD data complemented MBRN data to obtain a more complete count of all women giving birth after ART in Norway.

Use of Antidepressants and Risk of Cutaneous Melanoma: A Prospective Registry-Based Case-Control Study.

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.

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.

Distribution of allele frequencies for genes associated with physical activity and/or physical capacity in a homogenous Norwegian cohort- a cross-sectional study.

BACKGROUND: There are large individual differences in physical activity (PA) behavior as well as trainability of physical capacity. Heritability studies have shown that genes may have as much impact on exercise participation behavior as environmental factors. Genes that favor both trainability and participation may increase the levels of PA. The present study aimed to assess the allele frequencies in genes associated with PA and/or physical capacity, and to see if there is any association between these polymorphisms and self-reported PA levels in a cohort of middle-aged Norwegians of Scandinavian descent (n = 831; mean age mean age (± SD) 55.5 ± 3.8 years). RESULTS: The genotype distributions of the ACTN3 R577X, ACE I/D and MAOA uVNTR polymorphisms were similar to other populations of European descent. When comparing the genotype distribution between the low/medium level PA group (LMPA) and high level PA groups (HPA), a significant difference in ACTN3 577X allele distribution was found. The X allele frequency was 10% lower in the HPA level group (P = 0.006). There were no differences in the genotype distribution of the ACE I/D or MAOA uVNTR polymorphism. Education and previous participation in sports or outdoor activities was positively associated with the self-reported PA levels (P ≤ 0.001). CONCLUSIONS: To the best of our knowledge, this is the first study to report association between ACTN3 R577X genotype and PA level in middle-aged Scandinavians. Nevertheless, the contribution of a single polymorphism to a complex trait, like PA level, is likely small. Socioeconomic variables, as education and previous participation in sports or outdoor activities, are positively associated with the self-reported PA levels.

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.

Cancer trends and population structure in Norway 1990-2016. / Kreftutvikling og befolkningssammensetning i Norge 1990­2016.

BAKGRUNN: Befolkningssammensetningen i Norge har endret seg, og innvandrere utgjør nå nær 14 % av befolkningen. Vi vet ikke hvordan dette påvirker kreftbildet. I denne studien presenterer vi forekomst av kreft for den norskfødte delen av befolkningen for å kunne få et bilde på hvordan forekomsten har endret seg, sett bort fra effekten av innvandring. MATERIALE OG METODE: Data fra Kreftregisteret og populasjonsdata fra Statistisk sentralbyrå ble benyttet for å beregne aldersstandardiserte insidensrater av kreft i Norge i perioden 1990-2016. RESULTATER: Studiepopulasjonen besto av 6 703 675 personer, hvorav 82,3 % ble definert som norskfødte. Ratene for alle kreftformer samlet hos norskfødte og totalbefolkningen fulgte hverandre mer eller mindre jevnt. I siste femårsperiode (2012-16) var ratene for den norskfødte delen av befolkningen 2 % høyere enn de nasjonale ratene, og føflekk- og livmorhalskreft hadde den største prosentvise forskjellen med 6-8 % høyere rater. Raten for leverkreft var 3-4 % lavere for norskfødte sammenlignet med totalbefolkningen. FORTOLKNING: De nasjonale ratene har så langt gitt et godt bilde på kreftutviklingen i den norskfødte delen av befolkningen. Siden forskjellen mellom ratene økte mot slutten av tidsperioden, kan fødeland være en viktig faktor å ta hensyn til i presentasjonen av kreftforekomst.

Cancer risk in mother and child after fertility treatment. / Kreftrisiko hos mor og barn etter fertilitetsbehandling.

BAKGRUNN: I Norge fødes nå om lag 2 500 barn årlig etter fertilitetsbehandling. Hvorvidt behandlingen er forbundet med økt kreftrisiko, er fremdeles usikkert. KUNNSKAPSGRUNNLAG: Oversikten inkluderer kohortstudier om kreftrisiko hos kvinner behandlet med fertilitetsbehandling og barn unnfanget etter slik behandling. Et systematisk søk etter artikler ble gjort i EMBASE og Medline for perioden 2006-17. RESULTATER: Resultatene viser ingen generell økning i kreft hos kvinner som har fått fertilitetsbehandling. Hos barn antyder resultatene en tendens til økt risiko for hematologisk kreft, men ingen generell økt kreftrisiko. FORTOLKNING: Det er ingen entydige funn av forhøyet risiko for kreft hos kvinner som har gjennomgått fertilitetsbehandling, eller hos barn unnfanget etter slik behandling. Oppfølgingstiden er foreløpig kort, og det er behov for store befolkningsbaserte kohortstudier med lengre oppfølgingsperioder.