A protocol for prospective studies 5-hydroxyvitamin D, leptin and b ass index in relation to cutaneou elanoma incidence and survival

Introduction The incidence and mortality rates of cutaneous melanoma (CM) are increasing among fai skinned populations worldwide. Ultraviolet radiation s the principal risk factor for CM, but is also the mai source of 25-hydroxyvitamin D (25(OH)D), which has associated with reduced risk and better prognosis of cancer types. However, both low and high 25(OH)D l have been associated with increased risk of CM. Obe as measured by body mass index (BMI) is associated risk of several cancers and has also been suggested risk factor for CM, and may also be related to insuffi 25(OH)D and/or high leptin levels. Moreover, contract CM diagnosis has been associated with increased ri developing second cancer. We aim to study whether prediagnostic serum levels of 25(OH)D, high prediag evels of BMI and high serum leptin levels influence ncidence, Breslow thickness and CM mortality, and second cancer and survival after a CM diagnosis. Methods and analysis Cohort and nested case–co studies will be carried out using the population-base Janus Serum Bank Cohort (archival prediagnostic se BMI, smoking and physical activity), with follow-up fr 1972 to 2014. Additional data will be received from t Cancer Registry of Norway, the national Cause of De Registry, Statistics Norway (education and occupatio and exposure matrices of UVR. Time-to-event regres models will be used to analyse the cohort data, whil he nested case–control studies will be analysed by conditional logistic regression. A multilevel approach be applied when incorporating group-level data. Ethics and dissemination The project is approved he Regional Committee for Medical Research Ethics and is funded by the Norwegian Cancer Society. Res will be published in peer-reviewed journals, at scient conferences and in the news media

Anthropometric Factors and Cutaneous Melanoma: Prospective Data from the Population-based Janus Cohort

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population-based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972–2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non-linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking status. During a mean follow-up of 27 years, 3,000 incident CM cases were identified. In men, CM risk was positively associated with body mass index, body surface area (BSA), height and weight (all ptrends \u3c 0.001), and the exposure-response curves indicated an exponential increase in risk for all anthropometric factors. Weight loss of more than 2 kg in men was associated with a 53% lower risk (HR 0.47, 95% CI: 0.39, 0.57). In women, CM risk increased with increasing BSA (ptrend50.002) and height (ptrend \u3c 0.001). The shape of the height- CM risk curve indicated an exponential increase. Our study suggests that large body size, in general, is a CM risk factor in men, and is the first to report that weight loss may reduce the risk of CM among men

Craniofacial and dentoalveolar morphology in individuals with Prader–Willi syndrome: a case-control study

Background Prader–Willi syndrome (PWS) is a complex multisystem genetic disorder with distinct genetic and clinical features. Among other clinical symptoms, PWS is characterized by severe infantile hypotonia with feeding problems, childhood onset hyperphagia, obesity, scoliosis, short stature combined with growth hormone deficiency and developmental delay. PWS is associated with facial dysmorphology, orofacial dysfunction, oral abnormalities, low salivary flow and subsequent severe tooth wear. Little is known about the craniofacial growth direction or dental and skeletal relationships in individuals with PWS in different ages. The purpose of this study was to assess the craniofacial and dentoalveolar characteristics and to investigate the craniofacial growth direction separately in children, young adults and adults with PWS, using a cephalometric analysis of lateral cephalograms. Results Lateral cephalograms of 42 individuals with a confirmed genetic diagnosis of PWS were analysed and divided into three groups according to their age: Children ( 20 years). Cephalometric variables were compared between PWS patients and controls by age and sex. Significant deviations and distinct craniofacial patterns were found in children, young adults and adults with PWS compared with the control group. Children showed retrognatic mandible with a skeletal class II relationship, posterior growth direction and longer anterior face height. The young adults had smaller cranial base angle, a skeletal class II pattern and a higher anterior lower face than the control group. Adults with PWS had a prognathic mandible, skeletal class III relationship with anterior growth direction, more retroclined lower incisors and proclined upper incisors than the controls. Similar results were found when comparing the three groups with PWS; the adults had a prognathic mandible, skeletal class III pattern and anterior growth direction. Children had a retropositioned mandibula, skeletal class II relationship and posterior growth direction. Conclusion This study may contribute to a better understanding of the craniofacial growth pattern in children, young adults and adults with PWS and may have a clinical importance when planning dental treatment, such as prosthodontics and/or orthodontics

Harmonizing work history data in epidemiologic studies with overlapping employment records

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

Lifestyle associated factors and risk of urinary bladder cancer: A prospective cohort study from Norway.

A number of lifestyle associated factors, such as high body mass index (BMI), low physical activity, and related metabolic disorders, are associated with increased risk of cancer at several sites. For urinary bladder cancer (BC), such studies show inconsistent results, which could result from inadequate adjustment for smoking and occupational exposure. In the population‐based Janus Cohort (n = 292 851), we investigated the independent and combined impact of BMI, physical activity, blood pressure, and blood lipids on the risk of BC, by thorough adjustment for smoking and potential occupational exposure. We used cox proportional hazard regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between the lifestyle associated factors and BC risk. The associations observed were dependent on smoking status and gender. Among men, diastolic blood pressure (DBP) (HR 1.07, 95% CI 1.02‐1.12) and systolic blood pressure (SBP) (HR 1.04, 95% CI 1.01‐1.07) were positively associated with BC risk. Stratification by smoking status revealed a positive association between DBP and BC risk in never smokers (HR 1.14, 95% CI 1.00‐1.30), while no association was seen for current and former smokers. A risk score, integrating information across the lifestyle factors was positively associated with BC risk in men (ptrend = 0.043). In women, physical activity was associated with a decreased BC risk, but only among never smokers (HR 0.65, 95% CI 0.45‐0.94). In conclusion, relations between lifestyle associated factors and BC risk were most evident in never smokers, suggesting that smoking dominates the relation in current smokers

Vitamin D and vitamin D-binding protein and risk of bladder cancer: A nested case-control study in the Norwegian Janus Serum Bank Cohort

Background High circulating levels of vitamin D (25(OH)D) are suggested to reduce the risk of urinary bladder cancer (BC), but the evidence is weak, and several studies lack sufficient adjustment for potential confounders (e.g., smoking, body mass index (BMI), and physical activity). Moreover, few studies have investigated the role of vitamin D-binding protein (DBP) in this context. We conducted a matched nested case–control study including 378 cases and 378 controls within the Norwegian population-based Janus cohort, using serum collected 5–41 years prior to diagnosis, to study 25(OH)D and BC risk, by taking circulating DBP into account. Methods Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), for 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, an estimate of unbound (free) 25(OH)D levels. We adjusted for smoking (status and pack-years), BMI, physical activity, education and (mutually) for 25(OH)D and DBP. Restricted cubic splines were employed to examine nonlinear associations. Results High optimal levels of circulating 25(OH)D (≥100 nmol/L) (HR 0.35, 95% CI 0.19–0.64) were associated with decreased BC risk, when compared with insufficient concentrations (50–74 nmol/L). This association was less pronounced for optimal levels (75–99 nmol/L) (HR = 0.69, 95% CI 0.47–1.01). Moreover, estimated free 25(OH)D, was associated with decreased BC risk for molar ratio 17–21 (HR 0.66, 95% CI 0.44–0.97) and ≥22 (HR 0.50, 95% CI 0.29–0.82), compared to molar ratio 11–16. The HR function for BC risk was not linear, rather reversed u-shaped, with the highest HR at 62.5 nmol/L and 13.5 molar ratio, respectively. Conclusion High levels of total and estimated free 25(OH)D were associated with reduced risk of BC, compared with insufficient concentrations. DBP was not associated with BC risk. We did not observe any impact of DBP or any of the studied lifestyle factors on the association between 25(OH)D and BC

Genetic testing is essential for initiating statin therapy in children with familial hypercholesterolemia: Examples from Scandinavia

Background and aims In familial hypercholesterolemia (FH), statin treatment should be considered from 8 to 10 years of age, but the prevalence of statin use among children is not known. Methods Statin use (2008–2018) among children aged 10–14 and 15–19 years was obtained from the national prescription databases in Norway, Sweden and Denmark. We assumed that all statin users in these age groups had FH, and that the estimated prevalence of FH is 1 in 250 inhabitants. Changes in prevalence rates of statin use between 2008 and 2018 by country, age and sex were estimated using the Joinpoint Regression Program version 4.8.0.1. Differences in prevalence rate ratio each year between countries were analyzed using Poisson regression. Results Among children aged 10–14 years, there was a significant increase in statin use in Norway and Denmark between 2008 and 2018, while in Sweden an increase was only seen after 2014. Among children aged 15–19 years, an increase in statin use was only observed in Norway and Sweden between 2008 and 2018. Statin use was significantly more prevalent in Norway than in Sweden and Denmark each year, and in 2018 the proportion of children using statins was 4–5 times (10–14 years) and 3 times (15–19 years) higher in Norway compared with Sweden and Denmark. In 2018 in Norway, 19% and 35% of children aged 10–14 years and 15–19 years estimated to have FH used statins respectively; corresponding percentages in Sweden were 4.5% and 10%, and in Denmark 3% and 12%. In Norway, the increase in statin use between 2008 and 2018 roughly corresponded to the increase in children with genetically verified FH. Conclusions Between 2008 and 2018, statin use increased in children aged 10–19 years in Norway, Sweden and Denmark, but with large differences between the countries; statin use was 3–5 times more prevalent in Norway than in Sweden and Denmark, which may be due to a more widespread use of genetic testing for FH in Norway

Ultraviolet radiation and risk of cutaneous melanoma and squamous cell carcinoma in males and females in the Norwegian Offshore Petroleum Workers cohort

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 < 0.001), and sunscreen use (ptrend < 0.001). Conclusions Our results support associations between UVR exposure and skin cancer risk in male and female offshore petroleum workers. This occupational group may be especially relevant for targeted sun protection advice

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

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