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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

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.

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.

Background & Aims A gluten-free diet usually leads to mucosal remission in celiac disease, but persistent symptoms are common. A low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet is an established treatment for irritable bowel syndrome (IBS). We have assessed the efficacy of a moderately low FODMAP diet on persistent symptoms in treated celiac patients. Methods A randomized controlled trial was performed from 2018 to 2019 in 70 adults with biopsy-proven celiac disease. Inclusion criteria were as follows: persistent gastrointestinal symptoms defined by a Gastrointestinal Symptom Rating Scale (GSRS)–IBS version score of 30 or higher, gluten-free diet adherence for 12 months or longer, and serologic and mucosal remission. Participants were randomized to a low FODMAP–gluten-free diet (intervention) or usual gluten-free diet (control). The GSRS-IBS score was recorded at baseline and at weeks 1 to 4, and the Celiac Symptom Index at baseline and at week 4. Statistics included marginal models for repeated data and analyses of covariance. Results We included 34 participants in the intervention group and 36 in the control group. Time development of GSRS–IBS total scores differed significantly between the groups (Pinteraction < .001), evident after 1 week (mean difference in intervention vs control, -8.2; 95% CI, -11.5 to -5.0) and persisting through week 4 (mean difference in intervention vs control, -10.8; 95% CI, -14.8 to -6.8). Moreover, significantly lower scores were found for the dimensions of pain, bloating, diarrhea, and satiety (Pinteraction ≤ .04), but not constipation (Pinteraction = .43). FODMAP intake during the intervention was moderately low (mean, 8.1 g/d; 95% CI, 6.7–9.3 g/d). The Celiac Symptom Index was significantly lower in the intervention group at week 4 (mean difference, -5.8; 95% CI, -9.6 to -2.0). Conclusions A short-term moderately low FODMAP diet significantly reduced gastrointestinal symptoms and increased celiac disease–specific health, and should be considered for the management of persistent symptoms in celiac disease. ClinicalTrials.gov: NCT03678935.

Background Strict adherence to a gluten-free diet usually leads to clinical and histological remission in celiac disease. Few studies have investigated the prevalence of persistent symptoms in a celiac population. We aimed to study the impact of gastrointestinal symptoms on general health in a large number of treated celiac patients, and describe the prevalence of persistent gastrointestinal symptoms and investigate associated factors. Methods Adults with celiac disease filled out background questions, the Celiac Symptom Index (CSI) and the celiac disease adherence test (CDAT) in a web-based national survey. Participants who reported gastrointestinal symptoms during the previous week also recorded the gastrointestinal symptom rating scale-irritable bowel syndrome version (GSRS-IBS). Statistical analysis included chi-squared test, t-test, correlation, and linear regression. Results Of 3834 participants (82% women; mean age 47 years), 54% reported gastrointestinal symptoms the previous week, and 30% of these had CSI score ≥45, indicative of the relatively poor quality of life (vs. 5% among those without gastrointestinal symptoms). The prevalence of persistent gastrointestinal symptoms (GSRS-IBS ≥30) was 40% and the most prominent symptoms were bloating (44%) and pain (37%). Age, sex, symptoms at the time of diagnosis, comorbidity, dietary adherence and CeD-specific health were significantly associated with gastrointestinal symptoms (p

This is the peer reviewed version of the following article: Cervenka, I., Al Rahmoun, M., Mahamat-Saleh, Y., Fournier, A., Boutron-Ruault, M.-C., Severi, G. ... Kvaskoff, M. (2019). Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, which has been published in final form at https://doi.org/10.1002/ijc.32674. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

Objective The aim was to examine the influence of modified Atkins diet on serum concentration of antiepileptic drugs (AEDs). Methods Prospective data from 63 adult patients with either focal or generalized drug‐resistant epilepsy recruited to 12‐week dietary treatment as add‐on to AEDs are analyzed. AED serum concentrations, ketones, glucose, and hemoglobin A1c were measured before and after the dietary intervention. Paired t test was used and Spearman correlation coefficient, r, was estimated. Results Mean age was 37 years (range 16‐65 years). Mean serum concentrations of carbamazepine, clobazam, and valproate were significantly reduced after 4 and 12 weeks of the diet period (

Summary Background & aims The mechanisms behind non-coeliac gluten sensitivity (NCGS) are not fully understood although clinical symptoms have shown to subside after wheat withdrawal. Self-prescription of a gluten-free diet (GFD) without medical supervision is common in NCGS subjects, resulting in dietary restrictions that can cause macro- and micronutrient deficiencies. The primary aim was to describe dietary intake, including FODMAP, in subjects with self-reported gluten sensitivity on GFD in whom coeliac disease (CD) and wheat allergy were excluded. Secondary, clinical symptoms and health-related quality of life (HR-QoL) were examined. Methods Baseline characteristics were obtained from 65 adults with self-reported NCGS on GFD recruited to a randomised placebo-controlled challenge trial at Oslo University Hospital. Dietary intake was obtained by a seven-day food record and symptoms recorded by questionnaires. Results Mean proportions of energy were 43 E% from fat, 40 E% from carbohydrate and 17 E% from protein. Intakes of vitamin D, folic acid, calcium, iodine and iron were lower than recommended, mean (SD) 7.3 (5.8) μg, 235 (105) μg, 695 (309) mg, 81 (52) μg and 9.6 (7.5) mg, respectively. Mean (SD) intake of FODMAP was 11.6 g (8.7). Gastrointestinal symptoms as scored by 100 mm visual analogue scale (VAS) were all below 15 mm of which wind and bloating were the most expressed. Tiredness, concentration difficulties, fatigue and muscle/joint pain were scored highest among extra-intestinal symptoms. Gastrointestinal symptoms as scored by gastrointestinal symptom rating scale – irritable bowel syndrome version (GSRS-IBS) were correlated with mild depression (r = 0.43) and inversely correlated with five sub-domains of HR-QoL (−0.29 Conclusion Subjects with self-reported NCGS on GFD had high proportion of energy from fat and sub-optimal intakes of vitamin D, folic acid, calcium, iodine and iron. Despite GFD and moderate intake of FODMAP, the subjects reported various gastro- and extra-intestinal symptoms and reduced HR-QoL. The findings highlight the importance of dietary education and nutritional follow-up of subjects on GFD.

Elevated lipoprotein(a) (Lp(a)) is associated with CVD and is mainly genetically determined. Studies suggest a role of dietary fatty acids (FA) in the regulation of Lp(a); however, no studies have investigated the association between plasma Lp(a) concentration and n-6 FA. We aimed to investigate whether plasma Lp(a) concentration was associated with dietary n-6 FA intake and plasma levels of arachidonic acid (AA) in subjects with familial hypercholesterolaemia (FH). We included FH subjects with (n 68) and without (n 77) elevated Lp(a) defined as ≥75 nmol/l and healthy subjects (n 14). Total FA profile was analysed by GC–flame ionisation detector analysis, and the daily intake of macronutrients (including the sum of n-6 FA: 18 : 2n-6, 20 : 2n-6, 20 : 3n-6 and 20 : 4n-6) were computed from completed FFQ. FH subjects with elevated Lp(a) had higher plasma levels of AA compared with FH subjects without elevated Lp(a) (P = 0·03). Furthermore, both FH subjects with and without elevated Lp(a) had higher plasma levels of AA compared with controls (P < 0·001). The multivariable analyses showed associations between dietary n-6 FA intake and plasma levels of AA (P = 0·02) and between plasma levels of Lp(a) and AA (P = 0·006). Our data suggest a novel link between plasma Lp(a) concentration, dietary n-6 FA and plasma AA concentration, which may explain the small diet-induced increase in Lp(a) levels associated with lifestyle changes. Although the increase may not be clinically relevant, this association may be mechanistically interesting in understanding more of the role and regulation of Lp(a).

Evidence on sunscreen use and cutaneous squamous cell carcinoma (cSCC) risk is limited. Most studies have not taken sun protection factor (SPF) into consideration and used nonusers of sunscreen as the reference group. Nonusers are likely a priori at lower cSCC risk than users. No study has investigated the effect of high- versus low-SPF sunscreens on cSCC, appropriately adjusting for time-varying confounding. Using data from the Norwegian Women and Cancer Study (1991–2016), we investigated whether use of SPF ≥15 versus SPF

Physical activity (PA) is an important factor in cancer prevention, but positive association between PA and risk of cutaneous melanoma found in recent studies may complicate this strategy. Ultraviolet radiation (UVR) exposure during outdoor PA is a plausible explanation for a positive association. We investigated the associations between PA, UVR and melanoma risk in the Norwegian Women and Cancer cohort. Overall PA was reported by 151,710 women, aged 30–75 at inclusion, using a validated 10-point-scale at enrolment and during follow-up, together with recent numbers of sunburns, indoor tanning sessions and weeks on sunbathing vacations. Seasonal outdoor walking and seasonal PAs were recorded in subsamples (n = 102,671 and n = 29,077, respectively). Logistic and Cox regression were used. Mean follow-up was 18.5 years, and 1565 invasive incident melanoma cases were diagnosed. Overall PA was inversely associated with sunburns, while positively associated with sunbathing vacations and indoor tanning. Overall PA was not associated with melanoma risk in all body sites combined (ptrend = 0.61), but reduced risk was found in upper limb melanomas (hazard ratio (HR) = 0.70, 95% confidence interval (CI) 0.51–0.96; high versus low PA). Non-significant reduced risks were found for seasonal outdoor walking >2 h/day versus 30–60 min/day (summer HR = 0.81, 95% CI 0.66–1.00; autumn HR = 0.74, 95%CI 0.55–1.01). Seasonal PAs were not associated with melanoma risk. In conclusion, we found positive associations between overall PA and sunbathing vacations and indoor tanning, and, unlike literature, inverse association between overall PA and sunburns. Our results do not support a positive association between PA and melanoma risk in Norwegian women.

Background Pelvic girdle pain is prevalent during pregnancy, and women affected report weight-bearing activities to be their main disability. The Stork test is a commonly used single-leg-stance test. As clinicians report specific movement patterns in those with pelvic girdle pain, we aimed to investigate the influence of both pregnancy and pelvic girdle pain on performance of the Stork test. Methods In this cross-sectional study, 25 pregnant women with pelvic girdle pain, 23 asymptomatic pregnant and 24 asymptomatic non-pregnant women underwent three-dimensional kinematic analysis of the Stork test. Linear mixed models were used to investigate between-group differences in trunk, pelvic and hip kinematics during neutral stance, weight shift, leg lift and single leg stance. Findings Few and small significant between-group differences were found. Pregnant women with pelvic girdle pain had significantly less hip adduction during single leg stance compared to asymptomatic pregnant women (estimated marginal means (95% confidence intervals) -1.1° (−2.4°, 0.3°) and 1.0° (−0.4°, 2.4°), respectively; P = 0.03). Asymptomatic pregnant women had significantly less hip internal rotation compared to non-pregnant women 4.1° (1.6°, 6.7°) and 7.9° (5.4°, 10.4°), respectively (P = 0.04) and greater peak hip flexion angle of the lifted leg in single leg stance 80.4° (77.0°, 83.9°) and 74.1° (70.8°, 77.5°), respectively (P = 0.01). Variation in key kinematic variables was large across participants in all three groups. Interpretation Our findings indicate that trunk, pelvic and hip movements during the Stork test are not specific to pregnancy and/or pelvic girdle pain in the 2nd trimester. Instead, movement strategies appear unique to each individual.

Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose–response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03–1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02–1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04–1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01–1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02–1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose–response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.

Background Concerns have been raised that extensive use of personal care products that contain endocrine disrupting compounds increase the risk of hormone sensitive cancers. Objective To assess the effect of skincare product use on the risk of pre- and postmenopausal breast cancer, estrogen receptor positive (ER+) and negative (ER-) breast cancer and cancer of the endometrium. Methods We used data from 106,978 participants in the population-based Norwegian Women and Cancer cohort. Participants were categorized into non-, light, moderate, frequent and heavy users of skincare products based on self-reported use of hand and facial cream and body lotion. Cancer incidence information from the Cancer Registry of Norway was linked to individual data through the unique identity number of Norwegian citizens. Multivariable Cox proportional hazard regression was used to assess the effect of skincare product use on the risk of cancer of the breast and endometrium. We used multiple imputation by chained equations to evaluate the effect of missing data on observed associations. Results We found no associations between use of skincare products and incidence of premenopausal breast cancer (frequent/heavy versus non−/light use: hazard ratio [HR] =1.10, 95% confidence interval [CI]: 0.92–1.32), postmenopausal breast cancer (heavy versus light use: HR = 0.87, 95% CI: 0.65–1.18, frequent versus light use: HR = 0.97, 95% CI: 0.88, 1.07) or endometrial cancer (frequent/heavy versus non−/light use: HR = 0.97, 95% CI: 0.79–1.20). Use of skincare products did not increase the risk of ER+ or ER- breast cancer and there was no difference in effect across ER status (0.58 ≤ pheterogeneity ≤ 0.99). The magnitude and direction of the effect estimates based on complete case analyses and multiple imputation were similar. Conclusion Heavy use of skincare products, i.e. creaming the body up to two times per day during mid-life, did not increase the risk of cancer of the breast or endometrium.

Objective Ketogenic diets reduce seizures in children with drug-resistant epilepsy. Whether adults benefit from similar treatment has not been clarified. We therefore examined the efficacy of the modified Atkins diet in adults with drug-resistant focal epilepsy. Methods We performed a randomized clinical trial (RCT) with patients >16 years who had at least 3 seizures per month despite having tried at least 3 antiepileptic drugs. They were randomized to either 12 weeks on the modified Atkins diet (diet group) or habitual diet (control group). Primary endpoint was a change in seizure frequency from baseline to the intervention period, comparing those on diet with controls. Results We assigned 37 patients to the diet group and 38 to the control group. Nine of the patients in the diet group and 4 controls were excluded. Of those who completed the dietary intervention (n = 24), median seizure change was -1.0 (interquartile range [IQR] -13.7-8.8), while in the control group (n = 32) the median change was 4.5 (IQR -4.8-33.5). The median difference between the groups was -7.0 (95% confidence interval [CI] -37.0-3.0; P = .21). In the intention-to-treat analysis, the relative risk (RR) for achieving >50% seizure reduction was 1.8 (95% CI 0.3-10.2; P = .65), while for achieving >25% seizure reduction RR was 2.43 (95% CI 0.94-6.28; P = .06). We observed no serious adverse events. Significance In this RCT investigating the effect of an adjunctive modified Atkins diet on seizure frequency in adults with difficult-to-treat focal epilepsy, we found a significant reduction in seizure frequency in the diet group compared to the controls, but only for moderate benefit (>25% seizure reduction) among those who completed the intervention. However, seizure response varied considerably between individuals, perhaps negatively influenced by a drop in serum concentrations of antiepileptic drugs.

Postprandial hypertriacylglycerolaemia is associated with an increased risk of developing CVD. How fat quality influences postprandial lipid response is scarcely explored in subjects with familial hypercholesterolaemia (FH). The aim of this study was to investigate the postprandial response of TAG and lipid sub-classes after consumption of high-fat meals with different fat quality in subjects with FH compared with normolipidaemic controls. A randomised controlled double-blind cross-over study with two meals and two groups was performed. A total of thirteen hypercholesterolaemic subjects with FH who discontinued lipid-lowering treatment 4 weeks before and during the study, and fourteen normolipidaemic controls, were included. Subjects were aged 18–30 years and had a BMI of 18·5–30·0 kg/m2. Each meal consisted of a muffin containing 60 g (70 E%) of fat, either mainly SFA (40 E%) or PUFA (40 E%), eaten in a random order with a wash-out period of 3–5 weeks between the meals. Blood samples were collected at baseline (fasting) and 2, 4 and 6 h after intake of the meals. In both FH and control subjects, the level of TAG and the largest VLDL sub-classes peaked at 2 h after intake of PUFA and at 4 h after intake of SFA. No significant differences were found in TAG levels between meals or between groups (0·25≤P≤0·72). The distinct TAG peaks may reflect differences in the postprandial lipid metabolism after intake of fatty acids with different chain lengths and degrees of saturation. The clinical impact of these findings remains to be determined.

Background and aims Heart failure (HF) and atrial fibrillation/flutter (AF) are important causes of morbidity and mortality. Subjects with familial hypercholesterolemia (FH) carry a high risk of coronary artery disease (CAD) but it is not known if the risk of HF and AF is increased in FH. The present study investigated the incidence of hospitalization for HF and AF in a genetically verified FH cohort, age 25 years and older, compared to the general population. Methods Incidence rates of hospitalization for HF and AF were estimated from national registry data. Standardized incidence ratios (SIRs) were calculated. Results 4273 genotyped FH patients (51.7% women) with a total observation period of 18,300 patient years were studied. Overall, the expected number of FH patients with HF was 27.7 and the observed number of cases was 54 (SIR (95% CI) 2.0 (1.5–2.6)). The highest excess risk was observed in the age group 25–49 years, where SIRs were 3.8 (1.2–11.8) and 4.2 (2.0–8.8) in women and men, respectively. The total expected number of FH patients with AF was 39.4 while the observed number of cases was 77 (SIR 2.0 (1.6–2.4)). Among FH patients with an incident event of HF, nearly 90% had a previous diagnosis of CAD, and nearly 40% had suffered from a myocardial infarction. Conclusions We demonstrate a doubling of the risk of hospitalization for HF or AF in patients with FH. This is could have an important prognostic impact for patients and economic impact for the society.

Final version with altered title. Importance - No study, to our knowledge, has prospectively investigated a dose-response association between lifetime indoor tanning and risk of cutaneous squamous cell carcinoma (SCC). Objective - To investigate the dose-response association between lifetime indoor tanning and SCC risk, the association between duration of use and age at initiation with SCC risk, and the association between age at initiation and age at diagnosis. Design, Setting, and Participants - This cohort study included data from women born from 1927 to 1963 from the Norwegian Women and Cancer study, established in 1991 with follow-up through December 31, 2015. Baseline questionnaires were issued to participants from 1991 to 2007, with follow-up questionnaires given every 5 to 7 years. Data analysis was performed from January 2, 2018, to March 2, 2019. Exposures - Participants reported pigmentation factors. Sunburns, sunbathing vacations, and indoor tanning were reported for childhood, adolescence, and adulthood. Main Outcomes and Measures - Information on all cancer diagnoses and dates of emigration or death were obtained through linkage to the Cancer Registry of Norway, using the unique personal identification number of Norwegian citizens. Results - A total of 159 419 women (mean [SD] age at inclusion, 49.9 [8.3] years) were included in the study. During follow-up (mean [SD], 16.5 [6.4] years), 597 women were diagnosed with SCC. Risk of SCC increased with increasing cumulative number of indoor tanning sessions. The adjusted hazard ratio (HR) for highest use vs never use was 1.83 (95% CI, 1.38-2.42; P Conclusion and Relevance - The findings provide supporting evidence that there is a dose-response association between indoor tanning and SCC risk among women. The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation. These results support development of policies that regulate indoor tanning.

The long-term cholesterol-lowering effect of replacing intake of SFA with PUFA is well established, but has not been fully explained mechanistically. We examined the postprandial response of meals with different fat quality on expression of lipid genes in peripheral blood mononuclear cells (PBMC) in subjects with and without familial hypercholesterolaemia (FH). Thirteen subjects with FH (who had discontinued lipid-lowering treatment ≥4 weeks prior to both test days) and fourteen normolipidaemic controls were included in a randomised controlled double-blind crossover study with two meals, each with 60 g of fat either mainly SFA (about 40% energy) or n-6 PUFA (about 40% energy). PBMC were isolated in fasting, and 4 and 6 h postprandial blood samples. Expression of thirty-three lipid genes was analysed by reverse transcription quantitative PCR. A linear mixed model was used to assess postprandial effects between meals and groups. There was a significant interaction between meal and group for MSR1 (P = 0·03), where intake of SFA compared with n-6 PUFA induced a larger reduction in gene expression in controls only (P = 0·01). Intake of SFA compared with n-6 PUFA induced larger reductions in gene expression levels of LDLR and FADS1/2, smaller increases of INSIG1 and FASN, and larger increases of ABCA1 and ABCG1 (P = 0·01 for all, no group interaction). Intake of SFA compared with n-6 PUFA induced changes in gene expression of cholesterol influx and efflux mediators in PBMC including lower LDLR and higher ABCA1/G1, potentially explaining the long-term cholesterol-raising effect of a high SFA intake.

Post‐exertional malaise and delayed recovery are hallmark symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME /CFS ). Studies on repeated cardiopulmonary exercise testing (CPET ) show that previous exercise negatively affects oxygen uptake (VO 2) and power output (PO ) in ME /CFS . Whether this affects arterial lactate concentrations ([Laa]) is unknown. We studied 18 female patients (18–50 years) fulfilling the Canadian Consensus Criteria for ME /CFS and 15 healthy females (18–50 years) who underwent repeated CPET s 24 h apart (CPET 1 and CPET 2) with [Laa] measured every 30th second. VO 2 at peak exercise (VO 2peak) was lower in patients than in controls on CPET 1 (P < 0.001) and decreased in patients on CPET 2 (P < 0.001). However, the difference in VO 2peak between CPET s did not differ significantly between groups. [Laa] per PO was higher in patients during both CPET s (P interaction < 0.001), but increased in patients and decreased in controls from CPET 1 to CPET 2 (P interaction < 0.001). Patients had lower VO 2 (P = 0.02) and PO (P = 0.002) at the gas exchange threshold (GET , the point where CO 2 production increases relative to VO 2), but relative intensity (%VO 2peak) and [Laa] at GET did not differ significantly from controls on CPET 1. Patients had a reduction in VO 2 (P = 0.02) and PO (P = 0.01) at GET on CPET 2, but no significant differences in %VO 2peak and [Laa] at GET between CPET s. Controls had no significant differences in VO 2, PO or %VO 2peak at GET between CPET s, but [Laa] at GET was reduced on CPET 2 (P = 0.008). In conclusion, previous exercise deteriorates physical performance and increases [Laa] during exercise in patients with ME /CFS while it lowers [Laa] in healthy subjects.

The role of body weight change in survival among recipients of hematopoietic stem-cell transplantation is controversial. We assessed the effect of optimizing energy and protein intake on 1-year survival, body weight and body composition, and the effect of body weight and body composition on 1-year survival in 117 patients (57 intervention, 60 control) in a randomized controlled trial. Cox regression was used to study effects of the intervention, weight and body composition on death, relapse, and nonrelapse mortality (NRM). We found no significant effect of intervention versus control on death hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.54−2.04, p = 0.88), relapse (HR 1.15, 95% CI 0.48−2.27, p = 0.75), and NRM (HR 0.95, 95% CI 0.39−2.28, p = 0.90). Body weight, fat-free mass index, body fat mass index and total body water changed over time (p

This is the peer reviewed version of the following article: Støer, N.C., Botteri, E., Ghiasvand, R., Busund, M., Vangen, S., Lund, E. ... Weiderpass, E. (2019. Reproductive factors and risk of melanoma: a population-based cohort study. British Journal of Dermatology, 181(2), 282-289, which has been published in final form at https://doi.org/10.1111/bjd.17771. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Background - The association between reproductive factors and risk of cutaneous melanoma (CM) is unclear. We investigated this issue in the Norwegian Women and Cancer cohort study. Objectives - To examine the association between the reproductive factors age at menarche, menstrual cycle length, parity, age at first and last birth, menopausal status, breastfeeding duration and length of ovulatory life, and CM risk, overall and by histological subtypes and anatomical site. Methods - We followed 165 712 women aged 30–75 years at inclusion from 1991–2007 to the end of 2015. Multivariable Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results - The mean age at cohort enrolment was 49 years. During a median follow‐up of 18 years, 1347 cases of CM were identified. No reproductive factors were clearly associated with CM risk. When stratifying by histological subtype we observed significant heterogeneity (P = 0·01) in the effect of length of ovulatory life on the risk of superficial spreading melanoma (HR 1·02, 95% CI 1·01–1·04 per year increase) and nodular melanoma (HR 0·97, 95% CI 0·94–1·01 per year increase). When stratifying by anatomical site, menopausal status (HR 0·54, 95% CI 0·31–0·92, postmenopausal vs. premenopausal) and menstrual cycle length (HR 1·07, 95% CI 1·01–1·13, per day increase) were associated with CM of the trunk, and significant heterogeneity between anatomical sites was observed for menopausal status (P = 0·04). Conclusions - In this large population‐based Norwegian cohort study, we did not find convincing evidence of an association between reproductive factors and risk of CM.

IntroductionThe 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.

Finally version with altered title. Importance - Aortic valve stenosis (AS) is the most common valve disease. Elevated levels of low-density lipoprotein (LDL) cholesterol are a risk factor; however, lipid-lowering treatment seems not to prevent progression of AS. The importance of LDL cholesterol in the development of AS thus remains unclear. People with familial hypercholesterolemia (FH) have elevated LDL cholesterol levels from birth and until lipid-lowering treatment starts. Thus, FH may serve as a model disease to study the importance of LDL cholesterol for the development of AS. Objective - To compare the incidence of AS per year in all genetically proven patients with FH in Norway with the incidence of these diseases in the total Norwegian population of about 5 million people. Design, Setting, and Participants - This is a registry-based prospective cohort study of all Norwegian patients with FH with regard to first-time AS between 2001 and 2009. All genotyped patients with FH in Norway were compared with the total Norwegian populations through linkage with the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry regarding occurrence of first-time AS. Data were analyzed between January 1, 2018, and December 31, 2018. Main Outcomes and Measures - Standardized incidence ratios. Results - In total, 53 cases of AS occurred among 3161 persons (1473 men [46.6%]) with FH during 18 300 person-years of follow-up. Mean age at inclusion and at time of AS were 39.9 years (range, 8-91 years) and 65 years (range, 44-88 years), respectively. Total standardized incidence ratios were 7.9 (95% CI, 6.1-10.4) for men and women combined, 8.5 (95% CI, 5.8-12.4) in women, and 7.4 (95% CI, 5.0-10.9) in men, respectively, indicating marked increased risk of AS compared with the general Norwegian population. Conclusions and Relevance - In this prospective registry study, we demonstrate a marked increase in risk of AS in persons with FH.

BACKGROUND Walking difficulties are common among pregnant women with pelvic girdle pain. This cross-sectional study investigated the influence of pelvic girdle pain, pregnancy and speed on spatiotemporal and trunk, pelvic and hip kinematics during gait in the 2nd trimester of pregnancy. METHODS Three-dimensional gait analysis at self-selected speed was performed in 25 pregnant women with pelvic girdle pain, 24 asymptomatic pregnant and 24 non-pregnant women. Linear mixed models were used to investigate between-group differences in gait variables. Adjustment for gait speed was included in the analysis. Correlations between speed and fear of movement, disability and pain were examined using Spearman correlation coefficient (rs). FINDINGS Pregnant women with pelvic girdle pain walked 18% slower (estimated marginal means (95% confidence intervals) 1.18 (1.22, 1.24) meter/s) compared to asymptomatic pregnant women (1.44 (1.38, 1.50) meter/s) (P

Background: The condition non-coeliac gluten sensitivity (NCGS) is clinically similar to coeliac disease, but lack objective diagnostic criteria. Symptom relief on gluten-free diet followed by gluten containing food challenge may confirm the condition in clinical settings. Aim: To describe the results of an open bread challenge in patients with suspected NCGS, and to compare the results with recently suggested cut-offs for symptom change. Material and methods: Fifty-six patients (12 males) self-instituted on gluten-free diet with negative coeliac disease diagnostics were examined for NCGS by an open bread challenge. Symptoms were reported by Gastrointestinal Symptom Rating Scale, IBS-version (GSRS-IBS) and visual analogue scale (VAS). Results were retrospectively compared to the Salerno and Monash cut-offs for symptom change. Results: Forty-seven patients were diagnosed with NCGS. Total GSRS-IBS score and overall symptoms by VAS increased significantly in NCGS (p

Background Patients with familial hypercholesterolemia have increased cardiovascular disease mortality but the magnitude of the increased risk is uncertain. The primary aim of this study was to investigate all causes of death and place and manner of deaths in a large sample of genotyped familial hypercholesterolemia patients. Design, methods and results In this registry study data on 5518 patients with genotyped familial hypercholesterolemia were linked to the Norwegian Cause of Death Registry during 1992-2013. Standardized mortality ratios and 95% confidence intervals (CIs) were estimated. There were in total 189 deaths. Cardiovascular disease was the most common cause of death (42.3%). Mean age at cardiovascular disease death was 64.5 years (range 33-91). Cardiovascular disease mortality including all cardiovascular disease deaths mentioning any place on the death certificate was significantly higher in familial hypercholesterolemia patients compared to the general Norwegian population under 70 years of age. Standardized mortality ratio (95% CI) was highest in the 20-39 years age group; 4.12 (1.85-9.18) decreasing to 0.77 (0.50-1.19) for those over 80 years. For total cardiovascular disease deaths occurring out of hospital, standardized mortality ratio was 12.35 (5.14-29.70) for those aged 20-39 years. Conclusion Familial hypercholesterolemia patients under 70 years of age have significantly higher cardiovascular disease mortality compared to the general Norwegian population. For those aged 20-39 years the risk of cardiovascular disease deaths occurring out of hospital was increased 12-fold. In spite of genotyped familial hypercholesterolemia and premature cardiovascular disease deaths, the majority of all death certificates did not include familial hypercholesterolemia among any of the contributing causes of death.

Background Familial hypercholesterolaemia increases the risk for cardiovascular disease. The primary aim of the present study was to describe sex differences in incidence and prevalence of cardiovascular disease leading to hospitalisation in a complete cohort of genotyped familial hypercholesterolaemia patients. Design and methods In this registry study data on 5538 patients with verified genotyped familial hypercholesterolaemia were linked to data on all Norwegian cardiovascular disease hospitalisations, and hospitalisations due to pre-eclampsia/eclampsia, congenital heart defects and diabetes. Results During 1994-2009 a total of 1411 of familial hypercholesterolaemia patients were hospitalised, and ischaemic heart disease was reported in 90% of them. Mean (SD) age at first hospitalisation and first re-hospitalisation was 45.1 (16.5) and 47.6 (16.3) years, respectively, with no sex differences ( P = 0.66 and P = 0.93, respectively). More men (26.9%) than women (24.1%) with familial hypercholesterolaemia were hospitalised ( P = 0.02). The median (25th-75th percentile) number of hospital admissions was four (two to seven) per familial hypercholesterolaemia patient, with no sex differences ( P = 0.87). Despite having familial hypercholesterolaemia at the time of hospitalisation, the diagnosis of familial hypercholesterolaemia was registered in only 45.7% of the patients at discharge. Conclusion Most cardiovascular disease hospitalisations were due to ischaemic heart disease. Familial hypercholesterolaemia patients were first time hospitalised at age 45.1 years, with no significant sex differences in age, which are important novel findings. The awareness and registration of the familial hypercholesterolaemia diagnosis during the hospital stays were disturbingly low.

There are little long-term data on patients with familial hypercholesterolemia (FH) who initiated lipid-lowering therapy during childhood.To study long-term outcomes in young adults with FH who participated in clinical trials on lipid-lowering therapy during childhood.Participants in at least 1 of 6 clinical trials that took place between 1999 and 2008 were interviewed in 2011 or 2013. Frequency of medical consultations, use of lipid-lowering therapy, lipid levels, side effects, diet, tobacco use, and emotional issues were investigated using information from interviews, blood samples and medical records.Of the 118 individuals who participated in the trials, 67 (57%) were included. Median age was 25 years, and median time before follow-up was 10 years. Forty-eight (72%) participants were using statins at follow-up, 8 (12%) were also using ezetimibe, and 19 (28%) were not using any lipid-lowering therapy. Mean LDL-cholesterol (LDL-C) was 3.68 mmol/L in statin users and 6.08 mmol/L in non-users (P.001). Only 6 (9%) participants reached treatment goal, ie, an LDL-C ≤2.5 mmol/L. Participants who attended a consultation ≤2 years before follow-up had a significantly lower LDL-C compared with those who had a consultation2 years before follow-up (4.10 and 5.17 mmol/L, respectively; P = .02). Statin users had their last consultation more recently than non-users (median 1.4 and 2.2 years, respectively; P = .02).Statins are underused in this population, and most patients have not reached treatment goal. Those with recent consultations had lower LDL-C levels and were more often statin users. Therefore, yearly consultations for young adults with FH seem warranted.

Source at https://doi.org/10.1002/ijc.31854. Insulin‐like growth factor‐I (IGF‐I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF‐I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF‐I concentrations and melanoma risk. A nested case–control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF‐I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF‐I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF‐I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF‐I measured in adulthood and the risk of melanoma.

Background & aims: Reduced quality of life (QoL) is prevalent after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this randomized trial we examined the effect of individualized nutritional support during hospitalization for allo-HSCT. Primary outcome was change in global QoL three months post-HSCT with oral mucositis (OM) and acute graft-versus-host disease (aGVHD) as main secondary outcomes. Methods: Whereas the intervention group received recommended minimum daily intakes of 126 kJ/kg and 0.75 g protein/kg as food, supplements, enteral or parenteral nutrition, the controls received routine feeding. QoL was self-reported using the EORTC QLQ-C30 questionnaire. Results: Between August, 2010 and February, 2016, we randomized 59 and 60 patients to intervention and control, respectively; 40 and 48 being eligible for analysis of QoL. There was no difference between the two groups in mean global QoL after three months (-3.10, 95% 45 CI -11.90-5.69; P=0.49). Nor were there any differences in OM grades 3-4 (RR (vs grades 0-2), 1.11, 95% CI 0.59-2.11 and 0.95, 95% CI 0.72-1.25, respectively; P=0.78), or a GVHD grades 3 or 4 (RR (vs grades 0-2) 0.44, 95% CI 0·12-1.60; and 0.65, 95% CI 0.20-2.20, respectively; P=0.37). Conclusion: Individualized nutritional support with recommended energy and protein intakes during hospitalization had no effect on QoL, OM or aGVHD three months after allo-HSCT compared to routine nutrition. The study was funded by Oslo University Hospital and the Throne Holst Foundation, Norway.

Background: The Timed Up and Go (TUG) test, a standardized functional mobility test, has been proposed as a physical performance-based measure in pregnant women with pelvic girdle pain (PGP). Objectives: This cross-sectional study aimed to investigate physical function by the use of TUG in pregnant women with PGP compared to asymptomatic pregnant and non-pregnant women, and to identify factors associated with increased TUG. Methods: In total, 25 pregnant women with PGP, 24 asymptomatic pregnant and 25 asymptomatic non-pregnant women participated. One-way analysis of variance was used to explore difference in TUG between the groups and multiple linear regression analyses to explore associations between TUG and potential explanatory variables. Results: The time on TUG varied among pregnant women with PGP, and was significantly higher (mean (95% CI) 6.9 (6.5, 7.3) seconds) than for asymptomatic pregnant (5.8 (5.5, 6.0), p < 0.001) and non-pregnant (5.5 (5.4, 5.6), p < 0.001) women. In the total study sample, group, increased BMI and sick leave were significantly associated with increased TUG (p-values≤0.02). In pregnant women with PGP, pain intensity was the only significant clinical factor associated with increased TUG (p = 0.002). Conclusion: Pregnant women with PGP used longer time and showed larger variation in TUG than asymptomatic pregnant and non-pregnant women, this underpins that TUG targets activities relevant to PGP. Our results provide new knowledge about factors influencing TUG time. Importantly, multivariable analyses suggest that pain intensity should be considered when interpreting TUG time in pregnant women with PGP.

Background: Ecological studies have reported possible effects of sunlight on the risk of several diseases. Little evidence is available on the association between mortality and solar and artificial UV exposure by individual level from prospective studies. Methods: The Swedish Women's Lifestyle and Health cohort study included women aged 30 to 49 years in 1991–1992. Participants completed a questionnaire and were followed-up through linkages to national registries until the end of 2006. Cox models were used to estimate adjusted HRs and 95% CIs for all-cause mortality and for cancer and cardiovascular disease (CVD) mortality. Results: During 15 years of follow-up, among the 38,472 women included in the present study, 754 deaths occurred: 457 due to cancer and 100 due to CVD. When combining the information on sun exposure from age 10 to 39 years, women who got sunburned twice or more per year during adolescence had a reduced all-cause mortality, compared with women who had been sunburned once or less. A reduced risk for all-cause and CVD mortality was observed in women who went on sunbathing vacations more than once a year over three decades. Solarium use once or more per month for at least one decade increased the risk of all-cause mortality, when compared with women who never used a solarium. Conclusions: Solar UV exposure was associated with reduced overall and CVD mortality, whereas artificial UV exposure was associated with increased overall and cancer mortality among Swedish women. Impact: Moderate sun exposure may protect against cause-specific mortality. Cancer Epidemiol Biomarkers Prev; 20(4); 683–90. ©2011 AACR.

Background Errors in Breslow thickness reporting can give misclassification of T category, an important classifier in melanoma staging. Objective We sought to investigate precision (number of digits) and terminal digit clustering in Breslow thickness and potential consequences for T category. Methods All first primary and morphologically verified invasive melanomas in Norway between 2008 and 2015 were included. A smoothing model was fitted to estimate the underlying Breslow thickness distribution without digit clustering. Results Thickness was reported for 13,057 (97.5%) patients; the median was 1.0 mm (range, 0.09-85). It was reported as whole numbers (15.6%), to 1 decimal (78.2%) and 2 decimal places (6.2%)—thin tumors with more precision than thick tumors. Terminal digit clustering was found with marked peaks in the observed frequency distribution for terminal digits 0 and 5, and with drops around these peaks. Terminal digit clustering increased proportions of patients classified with T1 and T4 tumors and decreased proportions classified with T2 and T3. Limitations Breslow thickness was not reported in 2.5% of cases. Conclusions The Norwegian recommendation of measurement to the nearest 0.1 mm was not followed. Terminal digit clustering was marked, with consequences for T category. Pathologists, clinicians, and epidemiologists should know that clustering of thickness data around T category cut points can impact melanoma staging with consequent effect on patient management and prognosis.

ObjectiveThe primary objective was to study the risk of acute myocardial infarction (AMI) and coronary heart disease (CHD) in patients with familial hypercholesterolaemia (FH) and compare with the risk in the general population.MethodsPatients with an FH mutation but without prior AMI (n=3071) and without prior CHD (n=2795) were included in the study sample during 2001–2009. We obtained data on all AMI and CHD hospitalisations in Norway. We defined incident cases as first time hospitalisation or out-of-hospital death due to AMI or CHD. We estimated standardised incidence ratios (SIRs) with 95% CIs with indirect standardisation using incidence rates for the total Norwegian population stratified by sex, calendar year and 1 year age groups as reference rates.ResultsSIRs for AMI (95% CIs) were highest in the age group 25–39 years; 7.5 (3.7 to 14.9) in men and 13.6 (5.1 to 36.2) in women and decreased with age to 0.9 (0.4 to 2.1) in men and 1.8 (0.9 to 3.7) in women aged 70–79 years. Similarly, SIRs for CHD were highest among patients 25–39 years old; 11.1 (7.1–17.5) in men and 17.3 (9.6–31.2) in women and decreased 2.4 (1.4–4.2) in men and 3.2 (1.5–7.2) in women at age 70–79. For all age groups, combined SIRs for CHD were 4.2 (3.6–5.0) in men and 4.7 (3.9–5.7) in women.ConclusionPatients with FH are at severely increased risk of AMI and CHD compared with the general population. The highest excess risk was in the youngest group aged 25–39 years, in both sexes.

Background To better understand previous associations reported regarding nausea and vomiting in pregnancy (NVP) and pelvic girdle pain (PGP), an investigation into timing of symptom onset for NVP and PGP in pregnancy, as well as the association of NVP with PGP 4-6 months post-partum was performed. We hypothesised that women with NVP symptoms would be most susceptible to experiencing persistence of PGP post-partum. Methods Fifty two thousand six hundred seventy-eight pregnancies from the Norwegian Mother and Child Cohort Study were analysed regarding nausea, vomiting, pelvic girdle pain, and health outcome data collected from questionnaires answered between gestation weeks 15, 20, 30, and 6 months post-partum. Logistic regression was used. Results Women experiencing NVP and PGP together (6.9%) were heaviest in the sample, youngest at menarche and had highest proportion with education ≤12 years. The primiparous women in this group had the lowest timespan from menarche to pregnancy. Women with nausea alone (NP) and NVP had higher odds of PGP 4-6 months post-partum (adjusted odds ratio, aOR = 2.14, 95% CI 1.70–2.71, and aOR = 2.83, 95% CI 2.25–3.57, respectively), compared to symptom-free women. NP/NVP symptoms appeared early in the first trimester, while PGP symptoms appeared later in pregnancy. Women with longer durations of nausea and/or vomiting had a higher proportion of PGP compared to shorter duration women. Conclusions Women with NP and NVP had increased odds of PGP 4-6 months post-partum, and women with a long duration of nausea and/or vomiting had a higher proportion of PGP than women with shorter duration, both during pregnancy and 4-6 months post-partum. This finding suggests a synergistic relationship between NP/NVP and PGP.

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."

Source at https://doi.org/10.1001/jamadermatol.2018.3964. Importance: Two pathways have been hypothesized for the development of cutaneous melanoma: one typically affects the head and neck, a site with chronic sun damage, and the other affects the trunk, which is less exposed to the sun. However, the possible cause of limb melanomas is less studied under this hypothesis. Objective: To investigate the association between phenotypic characteristics, pattern of UV radiation exposure, and risk of melanoma on different body sites. Design, Setting, and Participants: This study used data on 161 540 women with information on phenotypic characteristics and UV radiation exposure who were part of the Norwegian Women and Cancer study, a population-based prospective study established in 1991 with exposure information collected by questionnaires at baseline and every 4 to 6 years during follow-up through 2015. Data analysis was performed from October 2017 through May 2018. Exposures: Participants reported hair color, eye color, untanned skin color, number of small symmetric and large asymmetric nevi, and freckling, as well as histories of sunburns, sunbathing vacations, and indoor tanning in childhood, adolescence, and adulthood. Main Outcomes and Measures: The Norwegian Women and Cancer study was linked to the Cancer Registry of Norway for data on cancer diagnosis and date of death or emigration. Primary melanoma site was categorized as head and neck, trunk, upper limbs, and lower limbs. Results: During follow-up of the 161 540 women in the study (mean age at study entry, 50 years [range, 34-70 years]; mean age at diagnosis, 60 years [range, 34-87 years]), 1374 incident cases of melanoma were diagnosed. Having large asymmetric nevi was a significant risk factor for all sites and was strongest for the lower limbs (relative risk [RR], 3.38; 95% CI, 2.62-4.38) and weakest for the upper limbs (RR, 1.96; 95% CI, 1.22-3.17; P = .02 for heterogeneity). Mean lifetime number of sunbathing vacations was significantly associated with risk of trunk melanomas (RR, 1.14; 95% CI, 1.07-1.22) and lower limb melanomas (RR, 1.12; 95% CI, 1.05-1.19) but not upper limb melanomas (RR, 0.98; 95% CI, 0.88-1.09) and head and neck melanomas (RR, 0.87; 95% CI, 0.73-1.04; P = .006 for heterogeneity). Indoor tanning was associated only with trunk melanomas (RR for the highest tertile, 1.49; 95% CI, 1.16-1.92) and lower limb melanomas (RR for the highest tertile, 1.33; 95% CI, 1.00-1.76; P = .002 for heterogeneity). Skin color, hair color, small symmetric nevi, and history of sunburns were associated with risk of melanoma on all sites. Conclusions and Relevance: These results appear to support the hypothesis of divergent pathways to melanoma and that recreational sun exposure and indoor tanning are associated with melanoma on the lower limbs, the most common site of melanoma in women. These findings appear to have important preventive implications.

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma, however epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multi-centre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma., In France, the E3N study was financially supported by the Mutuelle Générale de l'Education Nationale (MGEN), the European Community, the French League Against Cancer (LNCC); Gustave Roussy; and the French Institute of Health and Medical research (INSERM). EPIC-Greece was supported by the Hellenic Health Foundation. Support for EPIC Norfolk is from Medical Research Council UK and Cancer Research UK. EPIC-Italy was supported by the Italian Association for Cancer Research (AIRC).

The aims were to study: prevalence of pelvic girdle pain (PGP) one year postpartum; clinical course of PGP, physical functioning (PF) and bodily pain (BP) (from SF-36, 0 (worst) to 100 (best)) from gestation week (GW) 30 to one year postpartum; and whether findings at GW30 were associated with development of PF and BP from GW30 to one year postpartum. 215 pregnant women were followed from GW30 to one year postpartum. Clinical examination and questionnaire were used at GW30, questionnaire only were used at 12 weeks and one year postpartum. The women were categorised by GW30 clinical variables: self-reported PGP, pain locations in the pelvis and response to two clinical tests. Linear mixed models for repeated measures were used to study PF and BP during follow-up, within the categories of clinical variables. PGP prevalence remained unchanged from 12 weeks to one year postpartum (31-30%). PF and BP scores improved markedly from GW30 to 12 weeks postpartum, and marginally thereafter. Median PF scores were 70, 95 and 100 at GW30, 12 weeks and one year postpartum, respectively. Corresponding median BP scores were 52, 84 and 84. We found significant interactions between each clinical variable and time (P ≤ 0.01) for PF and BP. The most afflicted women at GW30 experienced largest improvement. Despite high PGP prevalence one year postpartum, most women recovered in terms of PF and BP scores. Unfavourable clinical course postpartum did not appear to depend on self-reported PGP, pain locations in the pelvis, or response to clinical tests at GW30.

Objective To investigate primarily the dietary intake, as well as demographics and selected lifestyle factors, of women experiencing nausea and vomiting in pregnancy, nausea only, or women who are symptom free. Design Prospective cohort study. Setting The Norwegian Mother and Child Cohort Study, a population-based pregnancy cohort. Sample Analyses were based on 51 675 Norwegian pregnancies. Methods Dietary intake was assessed by a self-reported food frequency questionnaire answered in the first trimester of pregnancy, as were data regarding nausea and vomiting. Chi-squared tests, one-way analysis of variance, and multiple linear regression were used. Main outcome measures Nausea and vomiting in pregnancy (NVP), gestational weight gain (GWG), and dietary intake. Results We found that 17 070 (33%) women experienced NVP, 20 371 (39%) experienced only nausea, and 14 234 (28%) were symptom free. Women with NVP were younger and heavier at pregnancy onset, with the lowest GWG and highest energy intake during pregnancy, primarily from carbohydrates and added sugars, compared with the other groups (P

Purpose To assess melanoma risk in relation to sunscreen use and to compare high– with low–sun protection factor (SPF) sunscreens in relation to sunbathing habits in a large cohort study. Materials and Methods We used data from the Norwegian Women and Cancer Study, a prospective population-based study of 143,844 women age 40 to 75 years at inclusion with 1,532,247 person-years of follow-up and 722 cases of melanoma. Multivariable Cox proportional hazards regression was used to estimate the association between sunscreen use (never, SPF < 15, SPF ≥ 15) and melanoma risk by calculating hazard ratios and 95% CIs. The population attributable fraction associated with sunscreen use was estimated. Results Sunscreen users reported significantly more sunburns and sunbathing vacations and were more likely to use indoor tanning devices. SPF ≥ 15 sunscreen use was associated with significantly decreased melanoma risk compared with SPF < 15 use (hazard ratio, 0.67; 95% CI, 0.53 to 0.83). The estimated decrease in melanoma (population attributable fraction) with general use of SPF ≥ 15 sunscreens by women age 40 to 75 years was 18% (95% CI, 4% to 30%). Conclusion Use of SPF ≥ 15 rather than SPF < 15 sunscreens reduces melanoma risk. Moreover, use of SPF ≥ 15 sunscreen by all women age 40 to 75 years could potentially reduce their melanoma incidence by 18%.

After the introduction of the prostate specific antigen (PSA) test in the 1980s, a sharp increase in the incidence rate of prostate cancer was seen in the United States. The age-specific incidence patterns exhibited remarkable shifts to younger ages, and declining rates were observed at old ages. Similar trends were seen in Norway. We investigate whether these features could, in combination with PSA testing, be explained by a varying degree of susceptibility to prostate cancer in the populations. We analyzed incidence data from the United States’ Surveillance, Epidemiology, and End Results program for 1973–2010, comprising 511,027 prostate cancers in men ≥40 years old, and Norwegian national incidence data for 1953–2011, comprising 113,837 prostate cancers in men ≥50 years old. We developed a frailty model where only a proportion of the population could develop prostate cancer, and where the increased risk of diagnosis due to the massive use of PSA testing was modelled by encompassing this heterogeneity in risk. The frailty model fits the observed data well, and captures the changing age-specific incidence patterns across birth cohorts. The susceptible proportion of men is $$39.9\,\%\,\left( {95\,\%\,{\text{CI}}\, 38.2, 41.6\,\% } \right)$$ in the United States and $$30.4\,\%\, \left( {95\,\%\, {\text{CI}} \,28.9, 32.0\,\% } \right)$$ in Norway. Cumulative incidence rates at old age are unchanged across birth cohort exposed to PSA testing at younger and younger ages. The peaking cohort-specific age-incidence curves of prostate cancer may be explained by the underlying heterogeneity in prostate cancer risk. The introduction of the PSA test has led to a larger number of diagnosed men. However, no more cases are being diagnosed in total in birth cohorts exposed to the PSA era at younger and younger ages, even though they are diagnosed at younger ages. Together with the earlier peak in the age-incidence curves for younger cohorts, and the strong familial association of the cancer, this constitutes convincing evidence that the PSA test has led to a higher proportion, and an earlier timing, of diagnoses in a limited pool of susceptible individuals.

Indoor tanning is associated with increased risk of melanoma, but most evidence comes from case-control studies. Using data from the Norwegian Women and Cancer Study, a large prospective cohort study, we investigated the associations of age at initiation of indoor tanning, duration of tanning-device use, and dose response with melanoma risk and examined the role of indoor tanning in age at melanoma diagnosis. We used Poisson regression to estimate relative risks and 95% confidence intervals for the relationship of indoor tanning to melanoma risk and linear regression to examine age of indoor tanning initiation in relation to age at diagnosis. During follow-up of 141,045 women (1991-2012; mean duration follow-up = 13.7 years), 861 women were diagnosed with melanoma. Melanoma risk increased with increasing cumulative number of tanning sessions (for highest tertile of use vs. never use, adjusted relative risk = 1.32, 95% confidence interval (CI): 1.08, 1.63); P-trend = 0.006. Age at initiation

The Armitage–Doll model with random frailty can fail to describe incidence rates of rare cancers influenced by an accelerated biological mechanism at some, possibly short, period of life. We propose a new model to account for this influence. Osteosarcoma and Ewing sarcoma are primary bone cancers with characteristic age–incidence patterns that peak in adolescence. We analyze Surveillance, Epidemiology and End Result program incidence data for whites younger than 40 years diagnosed during the period 1975–2005, with an Armitage–Doll model with compound Poisson frailty. A new model treating the adolescent growth spurt as the accelerated mechanism affecting cancer development is a significant improvement over that model. We also model the incidence rate conditioning on the event of having developed the cancers before the age of 40 years and compare the results with those predicted by the Armitage–Doll model. Our results support existing evidence of an underlying susceptibility for the two cancers among a very small proportion of the population. In addition, the modeling results suggest that susceptible individuals with a rapid growth spurt acquire the cancers sooner than they otherwise would have if their growth had been slower. The new model is suitable for modeling incidence rates of rare diseases influenced by an accelerated biological mechanism. Copyright © 2012 John Wiley & Sons, Ltd.

Most studies of cutaneous head and neck melanomas (CHNM) have reported poorer survival in CHNM compared with other sites, especially on the scalp/neck.We sought to compare patient and tumor characteristics between CHNM and cutaneous trunk and extremity melanomas and between CHNM locations (face/ear vs scalp/neck, anterior vs posterior), and to study prognostic factors in patients with CHNM.We studied all CHNM (n = 1074) from 8120 cases of cutaneous melanomas diagnosed in Norway in 2008 to 2012.Compared with cutaneous trunk and extremity melanomas, CHNM were more frequently found in men, more often nodular and lentigo maligna cutaneous melanomas, and diagnosed at higher T stage (P ≤ .01). CHNM located on posterior sites were diagnosed at significantly higher T stage, and were significantly more often diagnosed with ulceration and at more advanced stage compared with CHNM located on anterior sites (P .001). T stage and clinical stage were the only significant prognostic factors for melanoma-specific and overall death in the multivariable analysis (P .001).Low number of cases and the relatively high frequency of missing values are limitations.More advanced CHNM were diagnosed on posterior compared with anterior locations, but location was not a significant prognostic factor for cutaneous melanoma-specific or overall death in the multivariable models.

Background: Except for skin melanoma and nonmelanoma skin cancer, little evidence from prospective studies is available on the association between UV exposure and cancer risk. Methods: We followed prospectively 49,261 women aged 30 to 49 years at enrollment in 1991 to 1992 for 15 years. Cancer incidence was analyzed by fitting Cox models, and estimating hazard ratios (HR) and 95% confidence intervals (CI). Results: 2,303 incident cases of cancer were diagnosed (breast: 1,053, ovary: 126, lung: 116, colon-rectum: 133, and brain: 116). No associations were found between any cumulative measure of UV exposure at ages 10 to 39 years and overall cancer risk. However, spending ≥1 week/year between ages 10 and 29 years on sunbathing vacations led to an inverse association with overall cancer risk (HR: 0.70, 95% CI: 0.53–0.93) and breast cancer risk (HR: 0.56, 95% CI: 0.36–0.89) when compared with women who never went on such vacations. Solarium use was inversely associated with breast cancer risk, whereas ≥2 sunburns/year was inversely associated with lung cancer risk. No other associations were found between sun exposure or solarium use at ages 10 to 39 years and cancer risk. Conclusion: We found no evidence of an association between any cumulative measure of UV exposure at ages 10 to 39 years and overall cancer risk. UV exposure earlier in life was related to reduced overall and breast cancer risk. Impact: Further research is needed to define the amount of solar or artificial UV exposure that may, or may not, be beneficial for cancer prevention. Cancer Epidemiol Biomarkers Prev; 20(7); 1358–67. ©2011 AACR.

Vitamin D is well known for its important role in calcium and phosphor homeostasis. Recent research suggests that vitamin D also prevent some type of cancers. We studied solar vitamin D effective UV radiation (VD dose), dietary vitamin D, sun-seeking holidays, use of solarium, frequency of sunburn and breast cancer risk in a large population-based cohort study. A total of 41,811 women from the prospective Norwegian Women and Cancer Study, aged 40-70 years at baseline, were followed from 1997/1998 to 2007. Dietary vitamin D intake was calculated at baseline. Information on historical VD dose was used as a proxy for cutaneously obtained vitamin D status. Cox proportional hazards model was used. We adjusted for age, height, BMI, baseline menopausal status, use of hormone replacement therapy, use of oral contraception, alcohol, mother's history of breast cancer, mammography and parity. During 8.5 years of follow-up, 948 new cases of breast cancer were registered using data from the Norwegian Cancer Registry. We found no significant associations between VD dose, or vitamin D intake, or sun-seeking holidays, or use of solarium, or frequency of sunburn, and breast cancer risk. Relative risks (95% confidence intervals) for highest versus lowest category were 1.17 (0.95-1.44), 0.95 (0.75-1.21), 1.07 (0.87-1.32), 0.93 (0.76-1.14) and 1.10 (0.89-1.36), respectively. Our results do not support an association between vitamin D status, and breast cancer risk.

The objective of this prospective cohort study was to examine how results of clinical tests on women with pelvic girdle pain (PGP) in late pregnancy were associated with disability and pain intensity 12 weeks postpartum controlling for socio-demographical and psychological factors. Out of the 283 women clinically examined in gestation week 30, 179 were considered afflicted from PGP and constituted the study sample. Potential risk factors were assessed by questionnaires (at inclusion and in gestation week 30) and clinical examination in gestation week 30. The clinical examination included pain provocation tests for the pelvis as well as the active straight leg raise test. We used pain intensity and disability (disability rating index, DRI) as response variables, derived from questionnaires 12 weeks postpartum. Using multivariable linear regression analyses, sum of pain provocation tests and pre-pregnancy low back pain (LBP) were significantly associated with DRI 12 weeks postpartum. Furthermore, sum of pain provocation tests and number of pain sites were significantly associated with pain intensity. In conclusion, we found that when including results of clinical tests as risk factors together with socio-demographical and psychological factors in multivariable regression models, the clinical risk factors are the ones that remain significant. These results are of clinical importance because they seem to have the potential to identify women with a poor prognosis.