Cumulative exposure to estrogen may increase the risk of migraine in women.

BACKGROUND: Migraine is a common disorder, particularly affecting women during their reproductive years. This female preponderance has been linked to exposure to female sex hormones. METHODS: We used self-reported data from women born in 1943-1965 enrolled in the Norwegian Women and Cancer Study to examine the differences between women with migraine and women without migraine in a prospective design with respect to both endogenous and exogenous female sex hormone exposure. RESULTS: In total, 62,959 women were included in the study, of whom 24.8% reported previous migraine (n = 15,635). Using a Cox proportional hazards model, we found that higher age at menarche reduced the risk of migraine (hazards ratio (HR) = 0.96, 95% confidence interval (CI) = 0.95-0.98) and that oral contraceptive use and parity increased the risk of migraine (HR = 1.12, 95% CI = 1.06-1.18 and HR = 1.37, 95% CI = 1.29-1.46, respectively). CONCLUSIONS: Older age at menarche appears to reduce migraine risk, whereas oral contraceptive use and having children appear to increase the risk. Further research is required to investigate the causality of these associations.

Replacing red and processed meat with lean or fatty fish and all-cause and cause-specific mortality in Norwegian women. The Norwegian Women and Cancer Study (NOWAC): a prospective cohort study.

Nordic Nutrition Recommendations recommend reducing red and processed meat and increasing fish consumption, but the impact of this replacement on mortality is understudied. This study investigated the replacement of red and processed meat with fish in relation to mortality. Of 83 304 women in the Norwegian Women and Cancer Study (NOWAC) study, 9420 died during a median of 21·0 years of follow-up. The hazard ratios (HR) for mortality were estimated using Cox proportional hazards regression with analyses stratified on red and processed meat intake due to non-linearity. Higher processed meat (> 30 g/d), red and processed meat (> 50 g/d), and fatty fish consumption were associated with higher mortality, while red meat and lean fish consumption were neutral or beneficial. Among women with higher processed meat intake (> 30 g/d), replacing 20 g/d with lean fish was associated with lower all-cause (HR 0·92, 95 % CI 0·89, 0·96), cancer (HR 0·92, 95 % CI 0·88, 0·97) and CVD mortality (HR 0·82, 95 % CI 0·74, 0·90), while replacing with fatty fish was associated with lower CVD mortality (HR 0·87, 95 % CI 0·77, 0·97), but not with all-cause or cancer mortality. Replacing processed meat with fish among women with lower processed meat intake (≤ 30 g/d) or replacing red meat with fish was not associated with mortality. Replacing processed meat with lean or fatty fish may lower the risk of premature deaths in Norwegian women, but only in women with high intake of processed meat. These findings suggest that interventions to reduce processed meat intake should target high consumers.

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis.

PURPOSE: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. RESULTS: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. CONCLUSIONS: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).

The role of lifestyle factors in the association between education and self-reported fibromyalgia: a mediation analysis.

BACKGROUND: Socioeconomic status as measured by education, income, or occupation, has been associated with fibromyalgia but the underlying mechanism and the role of lifestyle factors are unclear. Thus, we examine the role of modifiable lifestyle factors (body mass index, physical activity, alcohol consumption and smoking) in the association between education and self-reported fibromyalgia. METHODS: We used data from 74,157 participants in the population-based prospective Norwegian Women and Cancer (NOWAC) study. Socioeconomic position, operationalized as years of educational attainment, and lifestyle factors were assessed via self-reported questionnaires. Multiple mediation analysis was used to decompose total effects into direct and indirect effects. Estimates were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The cumulative incidence of fibromyalgia was 3.2% after a median follow up time of 13 years. Fibromyalgia was inversely associated with years of educational attainment for ≤ 9 years (HR = 2.56; 95% CI 2.32-2.91) and for 10-12 years (HR = 1.84; 95% CI 1.72-2.02), compared with ≥ 13 years of education. Overall, all lifestyle factors together jointly mediated 17.3% (95% CI 14.3-21.6) and 14.1% (95% CI 11.3-18.9) of the total effect for ≤ 9 years and 10-12 years of education, respectively. Smoking and alcohol consumption contributed the most to the proportion mediated, for ≤ 9 years (5.0% and 7.0%) and 10-12 years (5.6% and 4.5%) of education. CONCLUSION: The association between education and self-reported fibromyalgia was partly explained through lifestyle factors, mainly smoking and alcohol consumption.

Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers: A retrospective nested case-control study in two prospective cohorts.

The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts.

Air Bubbles Activate Complement and Trigger Hemostasis and C3-Dependent Cytokine Release Ex Vivo in Human Whole Blood.

Venous air embolism, which may complicate medical and surgical procedures, activates complement and triggers thromboinflammation. In lepirudin-anticoagulated human whole blood, we examined the effect of air bubbles on complement and its role in thromboinflammation. Whole blood from 16 donors was incubated with air bubbles without or with inhibitors of C3, C5, C5aR1, or CD14. Complement activation, hemostasis, and cytokine release were measured using ELISA and quantitative PCR. Compared with no air, incubating blood with air bubbles increased, on average, C3a 6.5-fold, C3bc 6-fold, C3bBbP 3.7-fold, C5a 4.6-fold, terminal complement complex sC5b9 3.6-fold, prothrombin fragments 1+2 (PTF1+2) 25-fold, tissue factor mRNA (TF-mRNA) 26-fold, microparticle tissue factor 6.1-fold, ß-thromboglobulin 26-fold (all p < 0.05), and 25 cytokines 11-fold (range, 1.5-78-fold; all p < 0.0001). C3 inhibition attenuated complement and reduced PTF1+2 2-fold, TF-mRNA 5.4-fold, microparticle tissue factor 2-fold, and the 25 cytokines 2.7-fold (range, 1.4-4.9-fold; all p < 0.05). C5 inhibition reduced PTF1+2 2-fold and TF-mRNA 12-fold (all p < 0.05). C5 or CD14 inhibition alone reduced three cytokines, including IL-1ß (p = 0.02 and p = 0.03). Combined C3 and CD14 inhibition reduced all cytokines 3.9-fold (range, 1.3-9.5-fold; p < 0.003) and was most pronounced for IL-1ß (3.2- versus 6.4-fold), IL-6 (2.5- versus 9.3-fold), IL-8 (4.9- versus 8.6-fold), and IFN-γ (5- versus 9.5-fold). Antifoam activated complement and was avoided. PTF1+2 was generated in whole blood but not in plasma. In summary, air bubbles activated complement and triggered a C3-driven thromboinflammation. C3 inhibition reduced all mediators, whereas C5 inhibition reduced only TF-mRNA. Combined C5 and CD14 inhibition reduced IL-1ß release. These data have implications for future mechanistic studies and possible pharmacological interventions in patients with air embolism.

Labour market status and mortality risk: the Finnmark cohort study 1987-2017.

AIMS: The aim of this study was to investigate the age-varying mortality risk associated with different labour market status categories. METHODS: Data from a population-based survey carried out among adults aged 30-62 years in Finnmark in 1987/1988 were linked to the Norwegian Cause of Death Registry to identify all deaths occurring by December 2017. We used flexible parametric survival models to examine the age-varying associations between different labour market status categories (no paid work/homemaker, part-time work, full-time work, unemployment benefits, sick leave/rehabilitation allowance, and disability pension) and mortality. RESULTS: Men with part-time work, unemployment benefits, sick leave/rehabilitation allowance, or disability pension had an increased mortality risk compared with men with full-time work; however, these findings were restricted to ages below 60-70 years, varying with labour market status category. For women, excess mortality was linked to disability pension in the younger age groups; in older age groups it was linked to the labour market status category no paid work/homemaker. Non-employment was associated with low education level compared with full-time employment. CONCLUSIONS: The study showed increased mortality risk for some non-employment categories, with decreasing relative risk with age. Our findings suggest that the increased mortality risk is partly explained by health, pre-existing illnesses, and health-related behaviour and partly by other factors, such as social network and economic factors.

Lifestyle risk factors of self-reported fibromyalgia in the Norwegian Women and Cancer (NOWAC) study.

BACKGROUND: While the aetiology of fibromyalgia syndrome (FM) remains unknown, lifestyle factors have been linked to the disorder. However, there are few studies on the association between lifestyle factors and FM, thus we examine the risk of self-reported fibromyalgia given selected lifestyle factors. METHODS: We used data from 75,485 participants in the Norwegian Women and Cancer study. Information on FM and the lifestyle factors body mass index (BMI), physical activity level, smoking status/intensity, and alcohol consumption were obtained from baseline and follow-up questionnaires. We used Cox proportional hazards model to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: After a median follow-up time of 10 years, we observed 2,248 cases of self-reported fibromyalgia. Overweight (BMI 25-29.9 kg/m2) and obese (BMI ≥ 30 kg/m2) women had a relative risk of 1.34 (95% CI 1.21-1.47) and 1.62 (95% CI 1.41-1.87), respectively, compared to women with normal weight (BMI 18.5-24.9 kg/m2). Very low physical activity level (1-2) was associated with a 31% higher risk of self-reported fibromyalgia (HR 1.31, 95% CI 1.09-1.57) when compared to moderate physical activity level (5-6). There was a strong dose-response relationship between smoking status/intensity and self-reported fibromyalgia (p for trend < 0.001). Compared with moderate alcohol consumption (4.0-10 g/day), the risk of self-reported FM was 72% (HR 1.72; 95% CI 1.45-2.03) higher among teetotallers, and 38% (HR 1.38, 95% CI 1.23-1.54) higher among those with low consumption (0.1-3.9 g/day). CONCLUSIONS: Overweight and obesity, very low physical activity level, smoking, and alcohol consumption were associated with an increased risk of self-reported FM.

Overall lifestyle changes in adulthood are associated with cancer incidence in the Norwegian Women and Cancer Study (NOWAC) - a prospective cohort study.

BACKGROUND: Cancer is a leading cause of premature death worldwide and incidence is expected to rise in the coming decades. Many cohort studies, measuring lifestyle factors at one time-point, have observed that overall healthy lifestyles were inversely related to cancer incidence. However, there is little knowledge on the impact of lifestyle modification within adulthood. METHODS: Using the Norwegian Women and Cancer study, two repeated self-reported assessments of lifestyle behaviours were used to calculate healthy lifestyle index scores at each time-point (N = 66 233). The associations between change in healthy lifestyle index score and lifestyle-related cancer incidence, including alcohol-, tobacco-, obesity-, and reproductive-related, and site-specific breast and colorectal cancer incidence were estimated using Cox proportional hazard regression models. To assess nonlinearity in the dose-response relationships, restricted cubic spline models were used. RESULTS: Independent of baseline lifestyle, positive lifestyle changes were inversely related to the incidence of overall lifestyle-related cancers, as well as alcohol-related, tobacco-related, obesity-related, and reproductive-related cancers, but not breast and colorectal site-specific cancers. An association between lifestyle worsening and cancer incidence compared to stable lifestyle was observed. CONCLUSIONS: This study provides evidence that overall lifestyle changes among cancer-free women between the ages of 41 and 76 impact the incidence of many cancer types. Regardless of baseline lifestyle, there was a negative dose-response relationship between magnitude of positive lifestyle change and the incidence of overall lifestyle-related cancers. We observed that underlying this trend was an especially clear association between lifestyle worsening and increased risk compared to stable lifestyle. For adult women, maintaining a stable healthy lifestyle and lifestyle improvement are important for preventing the occurrence of many cancer types.

A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk.

BACKGROUND: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. OBJECTIVE: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. METHODS: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. RESULTS: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. CONCLUSIONS: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.

Non-linear associations between healthy Nordic foods and all-cause mortality in the NOWAC study: a prospective study.

BACKGROUND: The shape of the associations between intake of foods basic in a healthy Nordic diet and long-term health is not well known. Therefore, we have examined all-cause mortality in a large, prospective cohort of women in Norway in relation to intake of: Nordic fruits and vegetables, fatty fish, lean fish, wholegrain products, and low-fat dairy products. METHODS: A total of 83 669 women who completed a food frequency questionnaire between 1996 and 2004 were followed up for mortality until the end of 2018. Cox proportional hazards regression models were used to examine the associations between consumption of the Nordic food groups and all-cause mortality. The Nordic food groups were examined as categorical exposures, and all but wholegrain products also as continuous exposures in restricted cubic spline models. RESULTS: A total of 8 507 women died during the 20-year follow-up period. Nordic fruits and vegetables, fatty fish and low-fat dairy products were observed to be non-linearly associated with all-cause mortality, while higher intake of lean fish and wholegrain products reduced all-cause mortality. Intake levels and hazard ratios (HR) and 95% confidence intervals (CI) associated with lowest mortality were approximately 200 g/day of Nordic fruits and vegetables (HR 0.83 (95% CI: 0.77-0.91)), 10-20 g/day of fatty fish (10 g/day: HR 0.98 (95% CI: 0.94-1.02)) and 200 g/day of low-fat dairy products (HR 0.96 (95% CI: 0.81-1.01)) compared to no consumption. Consumption of fatty fish ≥ 60 g/day compared to no intake statistically significantly increased the mortality (60 g/day: HR 1.08 (95% CI: 1.01-1.16)), as did consumption of low-fat dairy products ≥ 800 g/day compared to no intake (800 g/day: HR 1.10 (95% CI: 1.02-1.20)). After stratification by smoking status, the observed association between Nordic fruits and vegetables and all-cause mortality was stronger in ever smokers. CONCLUSION: The associations between intake of foods basic in healthy Nordic diets and all-cause mortality may be non-linear. Therefore, assumptions of linear associations between traditional Nordic food groups and health outcomes could lead to wrong conclusions in analyses of healthy Nordic diets.

Seroprevalence of antibodies against SARS-CoV-2 in the adult population during the pre-vaccination period, Norway, winter 2020/21.

BackgroundSince March 2020, 440 million people worldwide have been diagnosed with COVID-19, but the true number of infections with SARS-CoV-2 is higher. SARS-CoV-2 antibody seroprevalence can add crucial epidemiological information about population infection dynamics.AimTo provide a large population-based SARS-CoV-2 seroprevalence survey from Norway; we estimated SARS-CoV-2 seroprevalence before introduction of vaccines and described its distribution across demographic groups.MethodsIn this population-based cross-sectional study, a total of 110,000 people aged 16 years or older were randomly selected during November-December 2020 and invited to complete a questionnaire and provide a dried blood spot (DBS) sample.ResultsThe response rate was 30% (31,458/104,637); compliance rate for return of DBS samples was 88% (27,700/31,458). National weighted and adjusted seroprevalence was 0.9% (95% CI (confidence interval): 0.7-1.0). Seroprevalence was highest among those aged 16-19 years (1.9%; 95% CI: 0.9-2.9), those born outside the Nordic countries 1.4% (95% CI: 1.0-1.9), and in the counties of Oslo 1.7% (95% CI: 1.2-2.2) and Vestland 1.4% (95% CI: 0.9-1.8). The ratio of SARS-CoV-2 seroprevalence (0.9%) to cumulative incidence of virologically detected cases by mid-December 2020 (0.8%) was slightly above one. SARS-CoV-2 seroprevalence was low before introduction of vaccines in Norway and was comparable to virologically detected cases, indicating that most cases in the first 10 months of the pandemic were detected.ConclusionFindings suggest that preventive measures including contact tracing have been effective, people complied with physical distancing recommendations, and local efforts to contain outbreaks have been essential.

The fraction of lung cancer attributable to smoking in the Norwegian Women and Cancer (NOWAC) Study.

BACKGROUND: We examined the association between active and passive smoking and lung cancer risk and the population attributable fraction (PAF) of lung cancer due to active smoking, in the Norwegian Women and Cancer Study, a nationally representative prospective cohort study. METHODS: We followed 142,508 women, aged 31-70 years, who completed a baseline questionnaire between 1991 and 2007, through linkages to national registries through December 2015. We used Cox proportional hazards models, to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We calculated PAF to indicate what proportion of lung cancer cases could have been prevented in the absence of smoking. RESULTS: During the more than 2.3 million person-years of observation, we ascertained 1507 lung cancer cases. Compared with never smokers, current (HR 13.88, 95% CI 10.18-18.91) smokers had significantly increased risk of lung cancer. Female never smokers exposed to passive smoking had a 1.3-fold (HR 1.34, 95% CI 0.89-2.01) non- significantly increased risk of lung cancer, compared with never smokers. The PAF of lung cancer was 85.3% (95% CI 80.0-89.2). CONCLUSION: More than 8 in 10 lung cancer cases could have been avoided in Norway, if the women did not smoke.

Open chest and pericardium facilitate transpulmonary passage of venous air emboli.

BACKGROUND: Transpulmonary passage of air emboli can lead to fatal brain- and myocardial infarctions. We studied whether pigs with open chest and pericardium had a greater transpulmonary passage of venous air emboli than pigs with closed thorax. METHODS: We allocated pigs with verified closed foramen ovale to venous air infusion with either open chest with sternotomy and opening of the pleura and pericardium (n = 8) or closed thorax (n = 16). All pigs received a five-hour intravenous infusion of ambient air, starting at 4-6 mL/kg/h and increased by 2 mL/kg/h each hour. We assessed transpulmonary air passage by transesophageal M-mode echocardiography and present the results as median with inter-quartile range (IQR). RESULTS: Transpulmonary air passage occurred in all pigs with open chest and pericardium and in nine pigs with closed thorax (56%). Compared to pigs with closed thorax, pigs with open chest and pericardium had a shorter to air passage (10 minutes (5-16) vs. 120 minutes (44-212), P < .0001), a smaller volume of infused air at the time of transpulmonary passage (12 mL (10-23) vs.170 mL (107-494), P < .0001), shorter time to death (122 minutes (48-185) vs 263 minutes (248-300, P = .0005) and a smaller volume of infused air at the time of death (264 mL (53-466) vs 727 mL (564-968), P = .001). In pigs with open chest and, infused air and time to death correlated strongly (r = 0.95, P = .001). CONCLUSION: Open chest and pericardium facilitated the transpulmonary passage of intravenously infused air in pigs.

Symptoms and signs of colorectal cancer, with differences between proximal and distal colon cancer: a prospective cohort study of diagnostic accuracy in primary care.

BACKGROUND: In an abdominal symptom study in primary care in six European countries, 511 cases of cancer were recorded prospectively among 61,802 patients 16 years and older in Norway, Denmark, Sweden, Netherlands, Belgium and Scotland. Colorectal cancer is one of the main types of cancer associated with abdominal symptoms; hence, an in-depth subgroup analysis of the 94 colorectal cancers was carried out in order to study variation in symptom presentation among cancers in different anatomical locations. METHOD: Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. Follow-up data were provided by the GP after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients. Fisher's exact test was used to analyse differences between groups. RESULTS: Almost all symptoms recorded could indicate colorectal cancer. 'Rectal bleeding' had a specificity of 99.4% and a PPV of 4.0%. Faecal occult blood in stool (FOBT) or anaemia may indicate gastrointestinal bleeding: when these symptoms and signs were combined, sensitivity reached 57.5%, with 69.2% for cancer in the distal colon. For proximal colon cancers, none of 18 patients had 'Rectal bleeding' at the initial consultation, but three of the 18 did so at a later consultation. 'Abdominal pain, lower part', 'Constipation' and 'Distended abdomen, bloating' were less specific and also less sensitive than 'Rectal bleeding', and with PPV between 0.7% and 1.9%. CONCLUSIONS: Apart from rectal bleeding, single symptoms did not reach the PPV 3% NICE threshold. However, supplementary information such as a positive FOBT or persistent symptoms may revise the PPV upwards. If a colorectal cancer is suspected by the GP despite few symptoms, the total clinical picture may still reach the NICE PPV threshold of 3% and justify a specific referral.

Coffee consumption and overall and cause-specific mortality: the Norwegian Women and Cancer Study (NOWAC).

Coffee consumption has previously been reported to reduce overall and cause-specific mortality. We aimed to further investigate this association by coffee brewing methods and in a population with heavy coffee consumers. The information on total, filtered, instant, and boiled coffee consumption from self-administered questionnaires was available from 117,228 women in the Norwegian Women and Cancer (NOWAC) Study. We used flexible parametric survival models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause, cardiovascular, and cancer mortality by total coffee consumption and brewing methods, and adjusted for smoking status, number of pack-years, age at smoking initiation, alcohol consumption, body mass index, physical activity, and duration of education. During 3.2 million person-years of follow-up, a total of 16,106 deaths occurred. Compared to light coffee consumers (≤ 1 cup/day), we found a statistically significant inverse association with high-moderate total coffee consumption (more than 4 and up to 6 cups/day, HR 0.89; 95% CI 0.83-0.94) and all-cause mortality. The adverse association between heavy filtered coffee consumption (> 6 cups/day) and all-cause mortality observed in the entire sample (HR 1.09; 95% CI 1.01-1.17) was not found in never smokers (HR 0.85; 95% CI 0.70-1.05). During the follow-up, both high-moderate total and filtered coffee consumption were inversely associated with the risk of cardiovascular mortality (HR 0.79; 95% CI 0.67-0.94; HR 0.80; 95% CI 0.67-0.94, respectively). The association was stronger in the analyses of never smokers (> 6 cups of filtered coffee/day HR 0.20; 95% CI 0.08-0.56). The consumption of more than 6 cups/day of filtered, instant, and coffee overall was found to increase the risk of cancer deaths during the follow-up. However, these associations were not statistically significant in the subgroup analyses of never smokers. The data from the NOWAC study indicate that the consumption of filtered coffee reduces the risk of cardiovascular deaths. The observed adverse association between coffee consumption and cancer mortality is most likely due to residual confounding by smoking.

Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study.

BACKGROUND: MicroRNAs (miRNAs) are promising biomarkers due to their structural stability and distinct expression profile in various cancers. We wanted to explore the miRNA expression in benign breast tissue and breast cancer subgroups in the Norwegian Women and Cancer study. METHODS: Specimens and histopathological data from study participants in Northern Norway diagnosed with breast cancer, and benign tissue from breast reduction surgery were collected. Main molecular subtypes were based on surrogate markers; luminal A (ER+ and/or PR+, HER2- and Ki67 ≤ 30%), luminal B (ER+ and/or PR+, HER2- and Ki67 > 30% or ER+ and/or PR+ and HER2+), HER2 positive (ER- and PR- and HER2+) and triple-negative (ER-, PR- and HER2-). RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue, and miRNAs were successfully analyzed in 102 cancers and 36 benign controls using the 7th generation miRCURY LNA microarray containing probes targeting all human miRNAs as annotated in miRBASE version 19.0. Validation with RT-qPCR was performed. RESULTS: On average, 450 miRNAs were detected in each sample, and 304 miRNAs were significantly different between malignant and benign tissue. Subgroup analyses of cancer cases revealed 23 miRNAs significantly different between ER+ and ER- tumors, and 47 miRNAs different between tumors stratified according to grade. Significantly higher levels were found in high grade tumors for miR-17-5p (p = 0.006), miR-20a-5p (p = 0.007), miR-106b-5p (p = 0.007), miR-93-5p (p = 0.007) and miR-25-3p (p = 0.015) from the paralogous clusters miR-17-92 and miR-106b-25. Expression of miR-17-5p (p = 0.0029), miR-20a-5p (p = 0.0021), miR-92a-3p (p = 0.011) and miR-106b-5p (p = 0.021) was significantly higher in triple-negative tumors compared to the rest, and miR-17-5p and miR-20a-5p were significantly lower in luminal A tumors. CONCLUSIONS: miRNA expression profiles were significantly different between malignant and benign tissue and between cancer subgroups according to ER- status, grade and molecular subtype. miRNAs in the miR-17-92 cluster and miR-17 family were overexpressed in high grade and triple-negative tumors associated with aggressive behavior. The expression and functional role of these miRNAs should be further studied in breast cancer to explore their potential as biomarkers in diagnostic pathology and clinical oncology.

Risk of lung cancer and physical activity by smoking status and body mass index, the Norwegian Women and Cancer Study.

We aimed to investigate physical activity (PA) and risk of different histological subtypes of lung cancer according to smoking status and body mass index using repeated measurements in a large cohort of women in Norway. The study sample for the multiple imputation analyses consisted of 86,499 and for the complete-case analysis 80,802 women. Repeated measurements of PA level, smoking habits, weight, and height were available for 54,691 women (63.2%), who were included in repeated measurement analyses combined with multiple imputation to address attrition. Cox proportional hazards regression models were used to calculate hazard ratios with 95% confidence intervals. During a median follow-up of 12.9 years, 866 cases of primary lung cancer were identified. We found an inverse association between PA and lung cancer overall. The results were consistent from multiple imputed data analysis to complete-case analysis of PA and possible confounders. We observed a similar trend for adenocarcinoma, but not for squamous cell or small cell carcinomas. Our findings suggest a more pronounced association between lung cancer overall and PA levels in current and former smokers, and in normal-weight and overweight participants with increasing PA levels. The potential of a modifiable lifestyle factor as PA to reduce the risk of lung cancer independently of smoking status is important in public health.

Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases. CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.

What makes women with food hypersensitivity do self-management work?

BACKGROUND: Managing a chronic condition takes work, and it is considered important that patients carry out this work. However, knowledge is lacking on what elements enhance self-management work. Persons with food hypersensitivity (FH) seem to do self-management work despite the relatively little support they receive. Our aim is to explore what makes women with FH carry out the work of managing their condition. Our research will shed light on the health care needs of women with FH and contribute to the knowledge on self-management among persons with chronic conditions. METHODS: We used the Self-determination theory and the Conservation of resources theory to analyze 16 qualitative individual interviews with women with FH aged 39-67 years. RESULTS: Our participants reported that eating selected foods resulted in uncomfortable symptoms, and their main motivation for carrying out self-management work was the wish to avoid these symptoms and their consequences. Participants' individual resources were crucial to the management of FH, and those who had a social network that included people with relevant competencies clearly benefited from this. Hindrances to the management of FH included competing priorities and not wanting to break with the social expectation of sharing a meal. CONCLUSIONS: Women with FH carried out self-management work because they were highly motivated. Important motivators included the uncomfortable symptoms that resulted from consuming some foods, which had negative consequences on their lives or could bring shame. The ability to perform self-management work was dependent on the availability of individual and social resources. Indeed, women with FH who have the individual and social resources necessary to manage their condition may not need health services, whereas those who do not have these resources, or have significant competing priorities, may need assistance from health services. The desire to avoid uncomfortable symptoms can be a motivator for persons with chronic conditions to do self-management work, while a lack of symptoms can reduce motivation. The competing role of basic needs can take two forms: when fulfilled, these needs may contribute to self-management work; however, people may opt out of self-management in order to fulfil basic needs.