The burden of colon cancer attributable to modifiable factors-The Norwegian Women and Cancer Study.

Colon cancer is the second most frequently diagnosed cancer in women in Norway, where incidence rates of colon cancer increased 3-fold between 1955 and 2014, for unknown reasons. We aimed to assess the burden of colon cancer attributable to modifiable risk factors in Norwegian women using the data from the Norwegian Women and Cancer (NOWAC) study. Self-reported information from 35 525 women from the NOWAC study were available. These included the following exposures: smoking status, alcohol consumption, body mass index, physical activity, intake of calcium, fibers, and red and processed meat. Colon cancer cases were identified from the Cancer Registry of Norway. A parametric piecewise constant hazards model was used to estimate the strength of exposure-cancer associations. Population attributable fractions with 95% confidence intervals (CIs) were calculated considering competing risk of death. The fraction of incident colon cancer attributable to ever smoking was 18.7% (95% CI 4.7%-30.6%), low physical activity 10.8% (95% CI -0.7% to 21.0%), alcohol consumption 14.5% (95% CI -2.8% to 28.9%), and low intake of calcium 10.0% (95% CI -7.8% to 24.8%). A small proportion of colon cancer cases was attributable to combined intake of red and processed meat over 500 g/week, overweight/obesity, and low intake of fibers. Jointly, these seven risk factors could explain 46.0% (95% CI 23.0%-62.4%) of the colon cancer incidence burden. Between 23% and 62% of the colon cancer burden among women in Norway was attributable to modifiable risk factors, indicating an important preventive potential of a healthy lifestyle.

Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study.

BACKGROUND: Classical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers. METHODS: We derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35-65 years at recruitment (1990-2000) in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 15.3 years, 47,110 incident cancer cases were recorded. PC1 (overall adiposity) was positively associated with the risk of overall cancer, with a HR per 1 standard deviation (SD) increment equal to 1.07 (95% confidence interval 1.05 to 1.08). Positive associations were observed with 10 cancer types, with HRs (per 1 SD) ranging from 1.36 (1.30-1.42) for endometrial cancer to 1.08 (1.03-1.13) for rectal cancer. PC2 (tall stature with low WHR) was positively associated with the risk of overall cancer (1.03; 1.02-1.04) and five cancer types which were not associated with PC1. PC3 (tall stature with high WHR) was positively associated with the risk of overall cancer (1.04; 1.03-1.05) and 12 cancer types. PC4 (high BMI and weight with low WC and HC) was not associated with overall risk of cancer (1.00; 0.99-1.01). CONCLUSIONS: In this multi-national study, distinct body shape phenotypes were positively associated with the incidence of 17 different cancers and overall cancer.

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.

Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score.

BACKGROUND: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. METHODS: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992-2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. RESULTS: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell's C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264-0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084-0.575)). CONCLUSIONS: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.

Physical activity and cutaneous melanoma risk: A Norwegian population-based cohort study.

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.

Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study.

BACKGROUND & AIMS: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC). METHODS: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection). RESULTS: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38-0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33-0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC. CONCLUSIONS: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity. LAY SUMMARY: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.

Physical activity and risk of endometrial cancer in the Norwegian Women and Cancer (NOWAC) study.

Few studies have investigated the association between endometrial cancer and physical activity (PA) using repeated measures of PA and different subtypes of endometrial cancer. We aimed to investigate the association between endometrial cancer and PA level at two points in time in women with different body mass index (BMI) profiles, and to calculate the population attributable fraction (PAF) of endometrial cancer for low PA levels. We included 82,759 women with complete information on PA at baseline in the Norwegian Women and Cancer Study; 52,370 had follow-up information on PA. 687 endometrial cancer cases were identified. Multivariate cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). The PAF indicated the proportion of endometrial cancer that could be avoided in the population if these women had a higher PA level. There was a statistically significant association between low PA levels at baseline and follow-up and endometrial cancer risk, with a dose-response trend (lowest PA level: HR = 1.60, 95% CI 1.16-2.20; highest PA level: HR = 0.73, 95% CI 0.45-1.16 compared to the median). Analyses that included follow-up measurements yielded similar results. 21.9% (95% CI 7.1-34.3) of endometrial cancers could be avoided if women with low PA levels (≤ 4 in a 1-10 degree self reported PA scale) increased their PA levels to 5-10. We found an inverse dose-response association between PA and endometrial cancer, independent of BMI. In this nationally representative cohort, 21.9% of endometrial cancers could potentially be avoided if PA levels increased to higher PA levels.

Mediating Role of Lifestyle Behaviors in the Association between Education and Cancer: Results from the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand whether the observed associations might be partially explained by lifestyle behaviors. METHODS: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level [measured through the Relative Index of Inequality (RII)] on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). RESULTS: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared with more educated participants. Mediation analyses showed that portions of the TE of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). CONCLUSIONS: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. IMPACT: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.

Criterion validity of a 10-category scale for ranking physical activity in Norwegian women.

BACKGROUND: Accurate measurement of physical activity (PA) is critical to establish dose-response relationships with various health outcomes. We compared the self-administered PA questionnaire from the Norwegian Women and Cancer Study (NOWAC) with a criterion method in middle-aged Norwegian women. METHODS: A sample of 177 randomly recruited healthy women attended two clinical visits approximately 4-6 months apart. At each visit, the women completed the NOWAC PA questionnaire (NOPAQ), rating their overall PA level on a 10-category scale (1 being a "very low" and 10 being a "very high" PA level) and performed an 8-minute step-test to estimate aerobic fitness (VO2max). After each visit, the women wore a combined heart rate and movement sensor for 4 consecutive days of free-living. Measures of PA obtained from the combined heart rate and movement sensor, which were used as criterion, included individually calibrated PA energy expenditure (PAEE), acceleration, and hours/day of moderate-to-vigorous intensity PA (MVPA). These were averaged between visits and compared to NOPAQ scores at visit 2. RESULTS: Intra-class correlation coefficients for objective measures from both free-living periods were in the range of 0.65-0.87 (P < 0.001), compared to 0.62 (P < 0.001) for NOPAQ. There was a moderate but significant (P < 0.001) Spearman's rank correlation coefficient in the range of 0.36-0.46 between NOPAQ and objective measures of PA. Linear trends for the association between the NOPAQ rating scale with PAEE, hours/day of MVPA and VO2max (P < 0.001) were also demonstrated. CONCLUSIONS: Self-reported PA level measured on a 10-category scale appears valid to rank PA in a female Norwegian population.

Life-Course Trajectories of Physical Activity and Melanoma Risk in a Large Cohort of Norwegian Women.

Purpose: Physical activity (PA) is a cornerstone in disease prevention and varies throughout life. A pooled analysis of cohort studies and a meta-analysis of cohort studies found positive associations between PA and melanoma risk. However, previous studies focused on PA at specific ages and often lacked information on ultraviolet radiation (UVR) exposure. Using the population-based Norwegian Women and Cancer (NOWAC) cohort, including information on PA and UVR exposure, we estimated life-course PA trajectories from adolescence to adulthood and their associations with melanoma. Methods: Total PA across different domains (recreation, occupation, transport, household) was reported for ages 14 and 30 years, and when responding to the questionnaire (31-76 years) using a 10-point scale, validated to rank PA levels in Norwegian females. We estimated life-course PA trajectories using a latent class mixed model in 152,248 women divided into three subcohorts depending on age at questionnaire completion: 31-39 (n = 27,098), 40-49 (n = 52,515) and ≥50 years (n = 72,635). The unique 11-digit identity number of Norwegian citizens was used to link NOWAC to the Cancer Registry of Norway for information on cancer diagnoses, emigration and death. Associations between PA trajectories and melanoma risk were estimated in each subcohort using multivariable Cox regression. Results: Five classes of individual life-course PA trajectories were identified in subcohort 31-39 years (low, moderate, high, decreasing, increasing PA) and four in subcohorts 40-49 and ≥50 years (low, moderate, high, decreasing PA). No significant association was found between life-course PA trajectories and melanoma risk in any subcohort. Hazard ratios (95% confidence intervals) for the high versus moderate trajectory were 0.92 (0.66-1.29), 1.15 (0.97-1.37) and 0.90 (0.78-1.05) for subcohorts 31-39, 40-49 and ≥50 years, respectively. Conclusion: Our results do not support a positive association between PA and melanoma risk found in previous studies, which is important for public health guidelines promoting regular PA.

Combined Lifestyle Behaviors and the Incidence of Common Cancer Types in the Norwegian Women and Cancer Study (NOWAC).

INTRODUCTION: Only a small number of studies have examined the impact of combined lifestyle behaviors on cancer incidence, and never in a Norwegian population. PURPOSE: To examine linear and nonlinear associations of combined lifestyle factors, assessed through a healthy lifestyle index (HLI), with the incidence of postmenopausal breast, colorectal, lung, postmenopausal endometrial, postmenopausal ovarian, pancreatic, and kidney cancer among women in Norway. METHODS: This prospective study included 96,869 women enrolled in the Norwegian Women and Cancer (NOWAC) cohort. Baseline information on lifestyle factors was collected between 1996 and 2004. The HLI was constructed from five lifestyle factors: physical activity level, body mass index, smoking, alcohol consumption, and diet. Each factor contributed 0 to 4 points to the HLI score, which ranged from 0 to 20, with higher scores representing a healthier lifestyle. Multiple imputation was used to handle missing data. Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Restricted cubic splines were used to examine nonlinearity in the associations. RESULTS: The HRs for a one-point increment on the HLI score were 0.97 (95% CI: 0.96-0.98) for postmenopausal breast cancer, 0.98 (0.96-1.00) for colorectal cancer, 0.86 (0.84-0.87) for lung cancer, 0.93 (0.91-0.95) for postmenopausal endometrial cancer, 0.99 (0.96-1.02) for postmenopausal ovarian cancer, 0.92 (0.89-0.95) for pancreatic cancer, and 0.94 (0.91-0.97) for kidney cancer. Nonlinearity was observed for the inverse associations between HLI score and the incidence of lung cancer and postmenopausal breast cancer. CONCLUSION: Based on our results, healthier lifestyle, as assessed by the HLI score, was associated with lower incidence of postmenopausal breast, colorectal, lung, postmenopausal endometrial, pancreatic, and kidney cancer among women, although the magnitude and linearity varied. Adoption of healthier lifestyle behaviors should be a public health priority to reduce the cancer burden among Norwegian women.

Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults.

IMPORTANCE: Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood. OBJECTIVE: To determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking. DESIGN, SETTING, AND PARTICIPANTS: We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015. EXPOSURES: Leisure-time physical activity of a moderate to vigorous intensity. MAIN OUTCOMES AND MEASURES: Incident cancer during follow-up. RESULTS: A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16-1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers. CONCLUSIONS AND RELEVANCE: Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.