Healthy lifestyle change and all-cause and cancer mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35-70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). RESULTS: After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. CONCLUSIONS: Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.

Association of Mediterranean diet with survival after breast cancer diagnosis in women from nine European countries: results from the EPIC cohort study.

BACKGROUND: The Mediterranean diet has been associated with lower risk of breast cancer (BC) but evidence from prospective studies on the role of Mediterranean diet on BC survival remains sparse and conflicting. We aimed to investigate whether adherence to Mediterranean diet prior to diagnosis is associated with overall and BC-specific mortality. METHODS: A total of 13,270 incident breast cancer cases were identified from an initial sample of 318,686 women in 9 countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adherence to Mediterranean diet was estimated through the adapted relative Mediterranean diet (arMED), a 16-point score that includes 8 key components of the Mediterranean diet and excludes alcohol. The degree of adherence to arMED was classified as low (score 0-5), medium (score 6-8), and high (score 9-16). Multivariable Cox proportional hazards models were used to analyze the association between the arMED score and overall mortality, and Fine-Gray competing risks models were applied for BC-specific mortality. RESULTS: After a mean follow-up of 8.6 years from diagnosis, 2340 women died, including 1475 from breast cancer. Among all BC survivors, low compared to medium adherence to arMED score was associated with a 13% higher risk of all-cause mortality (HR 1.13, 95%CI 1.01-1.26). High compared to medium adherence to arMED showed a non-statistically significant association (HR 0.94; 95% CI 0.84-1.05). With no statistically significant departures from linearity, on a continuous scale, a 3-unit increase in the arMED score was associated with an 8% reduced risk of overall mortality (HR3-unit 0.92, 95% CI: 0.87-0.97). This result sustained when restricted to postmenopausal women and was stronger among metastatic BC cases (HR3-unit 0.81, 95% CI: 0.72-0.91). CONCLUSIONS: Consuming a Mediterranean diet before BC diagnosis may improve long-term prognosis, particularly after menopause and in cases of metastatic breast cancer. Well-designed dietary interventions are needed to confirm these findings and define specific dietary recommendations.

The association between body fatness and mortality among breast cancer survivors: results from a prospective cohort study.

Evidence linking body fatness to breast cancer (BC) prognosis is limited. While it seems that excess adiposity is associated with poorer BC survival, there is uncertainty over whether weight changes reduce mortality. This study aimed to assess the association between body fatness and weight changes pre- and postdiagnosis and overall mortality and BC-specific mortality among BC survivors. Our study included 13,624 BC survivors from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, with a mean follow-up of 8.6 years after diagnosis. Anthropometric data were obtained at recruitment for all cases and at a second assessment during follow-up for a subsample. We measured general obesity using the body mass index (BMI), whereas waist circumference and A Body Shape Index were used as measures of abdominal obesity. The annual weight change was calculated for cases with two weight assessments. The association with overall mortality and BC-specific mortality were based on a multivariable Cox and Fine and Gray models, respectively. We performed Mendelian randomization (MR) analysis to investigate the potential causal association. Five-unit higher BMI prediagnosis was associated with a 10% (95% confidence interval: 5-15%) increase in overall mortality and 7% (0-15%) increase in dying from BC. Women with abdominal obesity demonstrated a 23% (11-37%) increase in overall mortality, independent of the association of BMI. Results related to weight change postdiagnosis suggested a U-shaped relationship with BC-specific mortality, with higher risk associated with losing weight or gaining > 2% of the weight annually. MR analyses were consistent with the identified associations. Our results support the detrimental association of excess body fatness on the survival of women with BC. Substantial weight changes postdiagnosis may be associated with poorer survival.

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.

Association between anthropometry and lifestyle factors and risk of B-cell lymphoma: An exposome-wide analysis.

To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.

Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.

Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study. METHODS: Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants. RESULTS: After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR1-sd 1.50, 95% CI 1.30-1.74), WC (OR1-sd 1.46, 95% CI 1.27-1.69), and WHR (OR1-sd 1.54, 95% CI 1.33-1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR1-sd: 1.26, 95% CI 1.07-1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06-0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05-0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32-0.87, p = 0.01). CONCLUSIONS: Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.

Physical activity in Sami and non-Sami populations in rural Northern Norway, the SAMINOR 2 Clinical Survey.

BACKGROUND: The Sami people is an indigenous minority population living in the northern parts of Norway and mainly in rural areas. We lack data of contemporary levels of physical activity (PA) in rural regions of Northern Norway and in the Sami population in particular. We aimed to describe the PA levels and investigate whether PA levels differs between Sami and non-Sami and between coastal and inland areas. METHODS: We used data from the second survey of the Population-based Study on Health and Living Conditions in Regions with Sami and Norwegian Populations - the SAMINOR 2 Clinical Survey (2012-2014) that includes the adult population in 10 municipalities in the counties Troms, Finnmark and Nordland. Participants self-reported on PA, ethnicity and modifiable lifestyle factors. Twelve thousand four hundred fifty-five individuals were invited with a response rate of 48.2% (n = 6004 participants). We tested differences using chi-square tests, two sample t-tests and linear regression models. RESULTS: Among 5628 participants, 41.1 and 40.9% of men and women, respectively, were defined as Sami. We found no ethnic differences in PA in men overall. However, Sami men living in Tana, and Nesseby reported higher PA compared to non-Sami men in the same area. For Sami women there was overall lower PA levels compared to non-Sami women, especially pronounced in Kautokeino/ Karasjok. CONCLUSION: This study showed small differences in PA levels between Sami and non-Sami men. Sami women had lower PA levels compared to their non-Sami counterparts. It is important to identify whether there are differences in various ethnic populations, together with other predictors for PA in future planning of public health interventions.

Healthy lifestyle and the risk of pancreatic cancer in the EPIC study.

Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants' shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e-09) and 0.77 (0.72, 0.82; ptrend = 1.7e-15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e-04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.

Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study.

BACKGROUND & AIMS: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision. METHODS: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests. RESULTS: After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors. CONCLUSIONS: The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.

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.

Physical activity before and after breast cancer diagnosis and survival - the Norwegian women and cancer cohort study.

BACKGROUND: The main aim of this study was to investigate pre- and post-diagnostic physical activity (PA) levels, as well as changes in pre- and post-diagnostic PA levels, and their association with all-cause and breast cancer-specific mortality in women with breast cancer. Our study will add to the knowledge on whether a modifiable behavior such as PA can improve survival. METHODS: We included 1,327 women with breast cancer from the population-based Norwegian Women and Cancer study, which enrolled women from 1991 to 2003. Breast cancer cases were identified through linkage to the Cancer Registry of Norway; date and cause of death were obtained from the National Register for Causes of Death through 31 December 2012. Self-reported pre- and post-diagnostic PA levels were assessed, and Cox proportional hazard regression and spline regression were used to evaluate the associations. RESULTS: Pre-diagnostic PA levels were not associated with all-cause or breast cancer-specific mortality. Post-diagnostic PA levels were associated with a significant trend (P<0.001) of decreased all-cause and breast cancer-specific mortality, which was stronger among older women (aged 50-74 years) and did not differ across categories of body mass index. All-cause mortality (hazard ratio [HR]=1.76, 95% confidence interval [CI] 1.21-2.56) and breast cancer-specific mortality (HR=2.05, 95% CI 1.35-3.10) increased among women who reduced their post-diagnostic PA level. These values were similar among women whose maintained an inactive PA level pre- and post-diagnosis. CONCLUSION: Overall, we observed a dose-response trend, with an inverse association between increased post-diagnostic PA level and all-cause and breast cancer-specific mortality, as well as a higher mortality risk among women who reduced their post-diagnostic PA levels. Our results are very promising for women with breast cancer, and indicate that health care professionals should consider adding PA as a part of primary cancer treatment.

Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study.

Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3 : 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3 : 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.

BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors--healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend<0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend<0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend<0.0001) for rectal cancer, respectively (P-difference by cancer sub-site=0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.

Physical activity and the risk of postmenopausal breast cancer - the Norwegian Women and Cancer Study.

BACKGROUND: The relationship between physical activity (PA) throughout life and the risk of postmenopausal breast cancer overall and by estrogen receptor (ER) and progesterone receptor (PR) status, has been reported, but without consistent results. The present study aimed to investigate PA from young age to adulthood in participants of the Norwegian Women and Cancer (NOWAC) Study, in order to determine whether changes in PA level affect the risk of postmenopausal breast cancer. METHODS: 1767 invasive breast cancer cases were identified among 80,202 postmenopausal participants of the NOWAC Study during 8.2 years of median follow-up. PA levels at age 14 years, 30 years and at cohort enrollment were obtained via a self-administered questionnaire. Multivariate Cox proportional hazard regression models were used to estimate relative risks and 95% confidence intervals of the risk of postmenopausal breast cancer overall and by ER/PR status. RESULTS: Risk of postmenopausal breast cancer overall and by ER/PR status was not associated with physical activity level at enrollment. Women with a low PA level at age 30 had an increased risk of ER+/PR + breast tumors (P for trend = 0.04) compared to women with a moderate physical activity level at age 30. Women with a low physical activity level at all three periods of life had a 20% significantly reduced risk of postmenopausal breast cancer, as well as a reduced risk of ER+/PR + and ER+/PR- breast tumors, compared with women who maintained a moderate physical activity level. However, when analyses were corrected for multiple tests, the result was no longer statistically significant. The findings were consistent over strata of age, body mass index and use of hormone replacement therapy. CONCLUSIONS: The study results from this large Norwegian cohort do not support an association between physical activity at different periods of life and the risk of postmenopausal breast cancer.

Associations Between Self-Rated Health and Mortality in the Norwegian Women and Cancer (NOWAC) Study.

Purpose: We investigated the association between self-rated health (SRH) and cancer incidence and SRH and all-cause mortality among Norwegian women. Population and Methods: We used data from 110,104 women in the Norwegian Women and Cancer (NOWAC) cohort aged 41-70 years at baseline. We used flexible parametric survival analysis with restricted cubic splines to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SRH and mortality in the entire cohort. We employed the same method in a multistate design to assess associations between baseline SRH and 1) cancer incidence, and 2) all-cause mortality in subgroups of women who did and did not receive a cancer diagnosis during follow-up. Results: With very good SRH as reference category for all associations and median age at end of follow-up, lower SRH was associated with increased mortality (HRgood SRH 1.19, 95% CI 1.12-1.26) and HRpoor SRH 1.81, 95% CI 1.66-1.97). Lower SRH at baseline was associated with cancer incidence (HRgood SRH 1.14, 95% CI 1.08-1.20 and HRpoor SRH 1.44, 95% CI: 1.32-1.58). Poor baseline SRH was associated with increased mortality for women who received a cancer diagnosis (HRpoor SRH 1.20, 95% CI 1.04-1.39), and SRH showed a strong association with increased mortality for women who stayed cancer free (HRgood SRH 1.59, 95% CI 1.44-1.77 and HRpoor SRH 3.34, 95% CI 2.91-3.84). Conclusion: Lower SRH at baseline predicted increased cancer risk and all-cause mortality in middle-aged to older women. Poor SRH at baseline predicted all-cause mortality in women who later received a cancer diagnosis. Both good and poor SRH at baseline predicted all-cause mortality in women who stayed cancer-free, and the association was stronger for these women compared to both the entire cohort and to women who were subsequently diagnosed with cancer.

On the use of the healthy lifestyle index to investigate specific disease outcomes.

The healthy lifestyle index (HLI), defined as the unweighted sum of individual lifestyle components, was used to investigate the combined role of lifestyle factors on health-related outcomes. We introduced weighted outcome-specific versions of the HLI, where individual lifestyle components were weighted according to their associations with disease outcomes. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the association between the standard and the outcome-specific HLIs and the risk of T2D, CVD, cancer, and all-cause premature mortality. Estimates of the hazard ratios (HRs), the Harrell's C-index and the population attributable fractions (PAFs) were compared. For T2D, the HR for 1-SD increase of the standard and T2D-specific HLI were 0.66 (95% CI: 0.64, 0.67) and 0.43 (0.42, 0.44), respectively, and the C-index were 0.63 (0.62, 0.64) and 0.72 (0.72, 0.73). Similar, yet less pronounced differences in HR and C-index were observed for standard and outcome-specific estimates for cancer, CVD and all-cause mortality. PAF estimates for mortality before age 80 were 57% (55%, 58%) and 33% (32%, 34%) for standard and mortality-specific HLI, respectively. The use of outcome-specific HLI could improve the assessment of the role of lifestyle factors on disease outcomes, thus enhancing the definition of public health recommendations.

Physical activity and risk of breast cancer overall and by hormone receptor status: the European prospective investigation into cancer and nutrition.

Physical activity is associated with reduced risks of invasive breast cancer. However, whether this holds true for breast cancer subtypes defined by the estrogen receptor (ER) and the progesterone receptor (PR) status is controversial. The study included 257,805 women from the multinational EPIC-cohort study with detailed information on occupational, recreational and household physical activity and important cofactors assessed at baseline. During 11.6 years of median follow-up, 8,034 incident invasive breast cancer cases were identified. Data on ER, PR and combined ER/PR expression were available for 6,007 (67.6%), 4,814 (54.2%) and 4,798 (53.9%) cases, respectively. Adjusted hazard ratios (HR) were estimated by proportional hazards models. Breast cancer risk was inversely associated with moderate and high levels of total physical activity (HR = 0.92, 95% confidence interval (CI): 0.86-0.99, HR = 0.87, 95%-CI: 0.79-0.97, respectively; p-trend = 0.002), compared to the lowest quartile. Among women diagnosed with breast cancer after age 50, the largest risk reduction was found with highest activity (HR = 0.86, 95%-CI: 0.77-0.97), whereas for cancers diagnosed before age 50 strongest associations were found for moderate total physical activity (HR = 0.78, 95%-CI: 0.64-0.94). Analyses by hormone receptor status suggested differential associations for total physical activity (p-heterogeneity = 0.04), with a somewhat stronger inverse relationship for ER+/PR+ breast tumors, primarily driven by PR+ tumors (p-heterogeneity < 0.01). Household physical activity was inversely associated with ER-/PR- tumors. The results of this largest prospective study on the protective effects of physical activity indicate that moderate and high physical activity are associated with modest decreased breast cancer risk. Heterogeneities by receptor status indicate hormone-related mechanisms.

Time trends in body height according to educational level. A descriptive study from the Tromsø Study 1979-2016.

OBJECTIVES: The objective of our study was to describe time trends in body height according to attained educational level in women and men in Norway. METHODS: We used previously collected data from six repeated cross-sectional studies in the population based Tromsø Study 1979-2016. Measured body height in cm and self-reported educational level were the primary outcome measures. We included 31 466 women and men aged 30-49 years, born between 1930 and 1977. Participants were stratified by 10-year birth cohorts and allocated into four groups based on attained levels of education. Descriptive statistics was used to estimate mean body height and calculate height differences between groups with different educational levels. RESULTS: Mean body height increased by 3.4 cm (95% confidence interval (CI) 3.0, 3.8) in women (162.5-165.9 cm) and men (175.9-179.3 cm) between 1930 and 1977. The height difference between groups with primary education compared to long tertiary education was 5.1 cm (95% CI 3.7, 6.5) in women (161.6-166.7 cm) and 4.3 cm (95% CI 3.3, 5.3) in men (175.0-179.3 cm) born in 1930-39. The height differences between these educational groups were reduced to 3.0 cm (95% CI 1.9, 4.1) in women (163.6-166.6 cm) and 2.0 cm (95% CI 0.9, 3.1) in men (178.3-180.3 cm) born in 1970-77. CONCLUSIONS: Body height increased in women and men. Women and men with long tertiary education had the highest mean body height, which remained stable across all birth cohorts. Women and men in the three other groups had a gradual increase in height by birth cohort, reducing overall height differences between educational groups in our study population.

A Smartphone-Based Information Communication Technology Solution for Primary Modifiable Risk Factors for Noncommunicable Diseases: Pilot and Feasibility Study in Norway.

BACKGROUND: Cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes are the 4 main noncommunicable diseases. These noncommunicable diseases share 4 modifiable risk factors (tobacco use, harmful use of alcohol, physical inactivity, and unhealthy diet). Short smartphone surveys have the potential to identify modifiable risk factors for individuals to monitor trends. OBJECTIVE: We aimed to pilot a smartphone-based information communication technology solution to collect nationally representative data, annually, on 4 modifiable risk factors. METHODS: We developed an information communication technology solution with functionalities for capturing sensitive data from smartphones, receiving, and handling data in accordance with general data protection regulations. The main survey comprised 26 questions: 8 on socioeconomic factors, 17 on the 4 risk factors, and 1 about current or previous noncommunicable diseases. For answers to the continuous questions, a keyboard was displayed for entering numbers; there were preset upper and lower limits for acceptable response values. For categorical questions, pull-down menus with response options were displayed. The second survey comprised 9 yes-or-no questions. For both surveys, we used SMS text messaging. For the main survey, we invited 11,000 individuals, aged 16 to 69 years, selected randomly from the Norwegian National Population Registry (1000 from each of the 11 counties). For the second survey, we invited a random sample of 100 individuals from each county who had not responded to the main survey. All data, except county of residence, were self-reported. We calculated the distribution for socioeconomic background, tobacco use, diet, physical activity, and health condition factors overall and by sex. RESULTS: The response rate was 21.9% (2303/11,000; women: 1397/2263; 61.7%, men: 866/2263, 38.3%; missing: 40/2303, 1.7%). The median age for men was 52 years (IQR 40-61); the median age for women was 48 years (IQR 35-58). The main reported reason for nonparticipation in the main survey was that the sender of the initial SMS was unknown. CONCLUSIONS: We successfully developed and piloted a smartphone-based information communication technology solution for collecting data on the 4 modifiable risk factors for the 4 main noncommunicable diseases. Approximately 1 in 5 invitees responded; thus, these data may not be nationally representative. The smartphone-based information communication technology solution should be further developed with the long-term goal to reduce premature mortality from the 4 main noncommunicable diseases.