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 < 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 (ptrend = 0.002) and height (ptrend < 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. This is the peer reviewed version of the article, which has been published in final form at Wiley. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Fructan, and not gluten, as symptom trigger in self-reported non-celiac gluten sensitivity.

Background & Aims: Non-celiac gluten sensitivity is characterized by symptom improvement after gluten withdrawal in absence of celiac disease. The mechanisms of non-celiac gluten sensitivity are unclear, and there are no biomarkers for this disorder. Foods with gluten often contain fructans, a type of fermentable oligo-, di-, monosaccharides and polyols. We aimed to investigate the effect of gluten and fructans separately in individuals with self-reported gluten sensitivity. Methods: We performed a double-blind crossover challenge of 59 individuals on a self-instituted gluten-free diet, for whom celiac disease had been excluded. The study was performed at Oslo University Hospital in Norway from October 2014 through May 2016. Participants were randomly assigned to groups placed on diets containing gluten (5.7 g), fructans (2.1 g), or placebo, concealed in muesli bars, for 7 days. Following a minimum 7-day washout period (until the symptoms induced by the previous challenge were resolved), participants crossed over into a different group, until they completed all 3 challenges (gluten, fructan, and placebo). Symptoms were measured by Gastrointestinal Symptom Rating Scale Irritable Bowel Syndrome (GSRS-IBS) version. A linear mixed model for analysis was used. Results: Overall GSRS-IBS scores differed significantly during gluten, fructan, and placebo challenges; mean values were 33.1 ± 13.3, 38.6 ± 12.3, and 34.3 ± 13.9, respectively (P = .04). Mean scores for GSRS-IBS bloating were 9.3 ± 3.5, 11.6 ± 3.5, and 10.1 ± 3.7, respectively, during the gluten, fructan, and placebo challenges (P = .004). The overall GSRS-IBS score for participants consuming fructans was significantly higher than for participants consuming gluten (P = .049), as was the GSRS bloating score (P = .003). Thirteen participants had the highest overall GSRS-IBS score after consuming gluten, 24 had the highest score after consuming fructan, and 22 had the highest score after consuming placebo. There was no difference in GSRS-IBS scores between gluten and placebo groups. Conclusions: In a randomized, double-blind, placebo-controlled crossover study of individuals with self-reported non-celiac gluten sensitivity, we found fructans to induce symptoms, measured by the GSRS-IBS. Clinicaltrials.gov no: NCT02464150

Prediagnostic serum 25-hydroxyvitamin D and melanoma risk

Abstract 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 HR imputed 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 &lt; 25 kg/m 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

Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population-based Janus Cohort

Background Breslow thickness is the most important prognostic factor of localized cutaneous melanoma (CM), but associations with anthropometric factors have been sparsely and incompletely investigated. Objectives To examine prediagnostic body mass index (BMI), body surface area (BSA), and height, weight and weight change in relation to Breslow thickness, overall and by anatomical site and histological subtype; and to assess possible nonlinear associations between these anthropometric factors and Breslow thickness. Methods CMs in the Janus Cohort were identified between 1972 and 2014. Linear regression was used to estimate geometric mean ratios (GMRs) of Breslow thickness with 95% confidence intervals (CIs) according to anthropometric factors. Restricted cubic splines in generalized linear models predicted adjusted mean Breslow thickness, and were used to assess possible nonlinear relationships. Results Of 2570 cases of CM, obese patients had a GMR of 1·16 (95% CI 1·04–1·30) of Breslow thickness vs. normal‐weight patients. For BSA and weight, quintile 5 showed GMRs of 1·13 (95% CI 1·00–1·27) and 1·17 (95% CI 1·03–1·33) of Breslow thickness vs. quintile 1, respectively. Associations seemed restricted to superficial spreading melanomas and CMs on the trunk and lower limbs. The associations plateaued at an adjusted mean Breslow thickness of about 2·5 mm (BMI 29 kg m−2, BSA 2·05 m2 and weight 90 kg), before declining for the highest values. No associations were found for height and weight change. Conclusions This large case‐series of incident CM demonstrated positive associations between BMI, BSA, weight and Breslow thickness, and suggested that behavioural or other mechanisms apply at high values. This is the peer reviewed version of the article, which has been published in final form at Wiley. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.