Post-diagnosis adiposity, physical activity, sedentary behaviour, dietary factors, supplement use and colorectal cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.

Based on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta-analyses to investigate the association of post-diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non-linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J-shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited-no conclusion). The evidence on recreational physical activity and lower risk of all-cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62-0.77) and recurrence/disease-free survival (RR: 0.80, 95% CI: 0.70-0.92) was graded as limited-suggestive. There was limited-suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), intake of whole grains and coffee with lower risk of all-cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all-cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited-no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well-designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients.

Operationalisation of a standardised scoring system to assess adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations in the UK biobank.

Introduction: In 2018, The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) published ten evidence-based Cancer Prevention Recommendations designed to reduce the risk of cancer via improved lifestyle behaviours. In 2019, Shams-White and colleagues created the "2018 WCRF/AICR Score" which aimed to standardise how adherence to these recommendations is assessed. The standardised scoring system includes seven of the recommendations concerning weight, physical activity and diet, with an optional eighth recommendation on breastfeeding. To promote transparency and reproducibility, the present paper describes the methodology for operationalisation of the standardised scoring system in the UK Biobank. Methods: UK Biobank recruited >500,000 individuals aged 37-73 years, between 2006 and 2010. In 2021, we held a workshop with experts which aimed to reach consensus on how to operationalise the scoring system using data available within UK Biobank. We used data on anthropometric measurements, physical activity and diet to calculate adherence scores. 24 h dietary assessment data were used to measure adherence to the following recommendations: "Eat a diet rich in wholegrains, vegetables, fruit, and beans", "Limit consumption of "fast foods" and other processed foods high in fat, starches or sugars" and "Limit consumption of sugar-sweetened drinks"; food frequency questionnaire data were used to assess adherence to "Limit consumption of red and processed meat" and "Limit alcohol consumption". Participants were allocated points for meeting, partially meeting or not meeting each recommendation, using cut-offs defined in the standardised scoring system. Results: At our workshop, discussions included the use of national guidelines to assess adherence to the recommendation on alcohol consumption, as well as challenges faced including defining the adapted ultra-processed food variables. A total score was calculated for 158,415 participants (mean 3.9 points, range 0-7 points). We also describe the methodology to derive a partial 5-point adherence score using data from the food frequency questionnaire in 314,616 participants. Conclusion: We describe the methodology used to estimate adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations for participants in the UK Biobank, including some of the challenges faced operationalising the standardised scoring system.

Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.

Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.

Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis.

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2  = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.

Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded 'limited-suggestive' likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality.

Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta-analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random-effects linear dose-response meta-analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta-analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta-analysis was only possible for all-cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25-hydroxyvitamin D (25(OH)D), and for breast cancer-specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces the risk of all-cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92-1.02), breast cancer-specific mortality (RR for high vs low: 0.83, 95% CI: 0.64-1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61-0.92); that dietary fibre intake decreases all-cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80-0.94); and that serum 25(OH)D is inversely associated with all-cause and breast cancer-specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89-0.97 and 0.94, 95% CI: 0.90-0.99, respectively). The remaining associations were graded as limited-no conclusion.

Different COVID-19 outcomes among systemic rheumatic diseases: a nation-wide cohort study.

OBJECTIVES: To investigate coronavirus disease 2019 (COVID-19)-associated risk of hospitalization and death in RA, AS, PsA, SLE and SSc in comparison with the general population during the first year of the pandemic, and compare their overall mortality with 2019. METHODS: Interlinking nationwide electronic registries, we recorded confirmed COVID-19-associated infections, hospitalizations and deaths, and all-cause deaths between 1 March 2020 and 28 February 2021 in all adults with RA, AS, PsA, SLE and SSc under treatment (n = 74 970, median age 67.5, 51.2, 58.1, 56.2 and 62.2 years, respectively) and in random comparators from the general population matched (1:5) on age, sex and region of domicile. Deaths from all causes during 2019 were also recorded. RESULTS: Compared with the general population, incidence rates (IR) for COVID-19-associated hospitalization were higher in RA [IR ratio (IRR) 1.71(1.50-1.95)], SLE [2.0 (1.4-2.7)] and SSc [2.28 (1.29-3.90)], while COVID-19-associated death rates were higher in RA [1.91 (1.46-2.49)]. When focusing only on severe acute respiratory syndrome coronavirus 2-infected subjects, after adjusting for age and gender, the odds ratio for COVID-19 associated death was higher in RA [1.47 (1.11-1.94)] and SSc [2.92 (1.07-7.99)] compared with the general population. The all-cause mortality rate compared with the general population increased in RA during the first year of the pandemic (IRR 0.71) with reference to 2019 (0.59), and decreased in SSc (IRR 1.94 vs 4.36). CONCLUSION: COVID-19 may have a more severe impact in patients with systemic rheumatic disease than in the general population. COVID-19-related mortality is increased in subgroups of patients with specific rheumatic diseases, underscoring the need for priority vaccination and access to targeted treatments.

Physical Activity and Health-Related Quality of Life in Women With Breast Cancer: A Meta-Analysis.

BACKGROUND: Physical activity (PA) is associated with improved health-related quality of life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund-American Institute for Cancer Research Continuous Update Project. METHODS: PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent expert panel graded the evidence. RESULTS: A total of 79 randomized controlled trials (14 554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy-Breast (WMD = 5.94, 95% confidence intervals [CI] = 2.64 to 9.24; I2 = 59%, n = 12), Functional Assessment of Cancer Therapy-General (WMD = 4.53, 95% CI = 1.94 to 7.13; I2 = 72%, n = 18), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (WMD = 6.78, 95% CI = 2.61 to 10.95; I2 = 76.3%, n = 17). The likelihood of causality was considered probable that PA improves HRQoL in breast cancer survivors. Effects were weaker for physical function and mental and emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions. CONCLUSION: PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental and emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.

Is lifestyle Modification the Key to Counter Chronic Diseases?

Dietary patterns, defined as the quantities, proportions, variety, or combination of different foods and drinks, as well as the frequency with which they are habitually consumed, are associated with an increased or decreased incidence of chronic diseases [...].

The 2018 World Cancer Research Fund/American Institute for Cancer Research Score and Cancer Risk: A Longitudinal Analysis in the NIH-AARP Diet and Health Study.

BACKGROUND: We examined associations between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations using the standardized 2018 WCRF/AICR Score and cancer risk among older U.S. adults. METHODS: Participants included 215,102 adults in the NIH-AARP Diet and Health Study followed between 2004 and 2011 (mean 7.0 person-years). Scores (range: 0-7 points) were calculated from self-reported weight, physical activity, and diet and alcohol intake measures. Outcomes included 17 cancers reviewed by WCRF/AICR (cases: male n = 11,066; female n = 8,865) and top three U.S. cancers in males (total n = 4,658; lung n = 2,211; prostate n = 920; colorectal n = 1,527) and females (total n = 5,957; lung n = 1,475; post-menopausal breast n = 3,546; colorectal n = 936). Cox proportional hazard ratios (HRs) were estimated for score and cancer risk associations, stratifying by sex and smoking status. RESULTS: Each one-point score increase was associated with 6% to 13% reduced cancer risk across combined outcomes, except for male never smokers' risk for top three cancers and male current smokers' risk for both combined cancer outcomes. Higher scores were associated with decreased lung cancer risk only among male former smokers (HR, 0.84; 95% CI, 0.79-0.89) and female current smokers (HR, 0.89; 95% CI, 0.82-0.96). Higher scores were associated with 7% to 19% decreased breast cancer risk across smoking strata and 10% to 14% decreased colorectal cancer risk among male and female never and former smokers. CONCLUSIONS: Greater recommendations adherence was associated with reduced cancer risk. IMPACT: Findings emphasize the importance of considering combined contributions of multiple lifestyle factors for cancer prevention among older adults and the potential modifying role of smoking history.

The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score and All-Cause, Cancer, and Cardiovascular Disease Mortality Risk: A Longitudinal Analysis in the NIH-AARP Diet and Health Study.

Background: The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) published Cancer Prevention Recommendations in 2018 focused on modifiable lifestyle factors. Objectives: The aim was to examine how adherence to WCRF/AICR recommendations via the 2018 WCRF/AICR score is associated with risk for all-cause, cancer, and cardiovascular disease (CVD) mortality outcomes among older US adults. Methods: Baseline and follow-up questionnaire data (n = 177,410) were used to calculate weight, physical activity, and diet components of the 2018 WCRF/AICR score (0-7 total points). Adjusted HRs and 95% CIs were estimated, stratified by sex and smoking status. Results: There were 16,055 deaths during a mean of 14.2 person-years. Each 1-point score increase was associated with a 9-26% reduced mortality risk for all outcomes, except for current male smokers' cancer mortality risk. When the score was categorized comparing highest (5-7 points) with lowest (0-2 points) scores, associations with reduced all-cause mortality risk were strongest in former smokers (HRmales: 0.51; 95% CI: 0.43, 0.61; HRfemales: 0.38; 95% CI: 0.31, 0.46), followed by current smokers (HRmales: 0.55; 95% CI: 0.34, 0.89; HRfemales: 0.44; 95% CI: 0.32, 0.59) and never smokers (HRmales: 0.57; 95% CI: 0.47, 0.70; HRfemales: 0.50; 95% CI: 0.41, 0.60). An association with cancer mortality risk was also seen in former smokers (HRmales: 0.59; 95% CI: 0.43, 0.81; HRfemales: 0.52; 95% CI: 0.37, 0.73) and female current (HRfemales: 0.55; 95% CI: 0.32, 0.96) and never (HRfemales: 0.57; 95% CI: 0.40, 0.80) smokers; findings were not statistically significant in other strata. For CVD mortality, highest compared with lowest scores were associated with a 49-73% risk reduction, except in male never and current smokers. In exploratory analysis, physical activity, body weight, alcohol, and plant-based foods were found to be predominant components in the score. Conclusions: Greater 2018 WCRF/AICR scores were associated with lower mortality risk among older adults. Future research can explore how smoking modifies these relations, and further examine different populations and other cancer-relevant outcomes.

Prevalence and patterns of anti-osteoporotic drug use based on 2019 real-world nationwide data in Greece.

We used the Greek nationwide database to capture individuals on anti-osteoporotic treatment during 2019. From the estimated number of 683,679 osteoporotic individuals, only 42% were receiving treatment, with the total annual cost being almost one-tenth of the total cost of fractures. The treatment gap was significantly higher in males than in females. INTRODUCTION: Based on the 2019 European scorecard (SCOPE), osteoporosis is diagnosed in an estimated 683,679 individuals in Greece, with the direct cost of incident fractures being €694.7 million, although further relevant real-world data are scarce. METHODS: The e-Government Center for Social Security Services prescription database, which covers almost 100% of the Greek population, was used to capture all individuals on anti-osteoporotic treatment during 2019. RESULTS: A total of 288,983 among 8,641,341 people, corresponding to 3.3% of the total adult Greek population, had filled at least one anti-osteoporotic prescription (6.0% and 0.36% for females and males, respectively). Prevalence of anti-osteoporotic treatment increased with age, from 0.15% in those younger than 50 to 8.6% in those older than 70 years. Oral bisphosphonates were more frequently prescribed (58.8%), followed by denosumab (39.4%). Alendronate was more frequently prescribed in males and in people younger than 60 years. Denosumab was more frequently prescribed in females and in people older than 60 years. Selective estrogen-receptor modulators, teriparatide, and parenteral bisphosphonates accounted for 1.1%, 1.0%, and 0.02% of all prescriptions, respectively. Orthopedic surgeons (39.6%), endocrinologists (19.6%), general practitioners (19%), and rheumatologists (9.3%) prescribed the vast majority of anti-osteoporotic regimens, with significant differences in prescription patterns. The annual cost of treatment per patient increased significantly with age, being on average €323.33. CONCLUSIONS: Less than half of the estimated number of individuals with osteoporosis in 2019 in Greece received treatment, with the total annual cost being far less than the estimated cost of incident-fragility fractures. The impact of this undertreatment on related health care costs merits further investigation.

All-cause mortality in systemic rheumatic diseases under treatment compared with the general population, 2015-2019.

OBJECTIVES: To compare current all-cause mortality rates in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) versus general population. METHODS: In this population-based, retrospective cohort study, anonymised data on 11 186 586 citizens, including all patients with RA (42 735, 79% female), AS (9707, 43% female), PsA (13 779, 55% female), SLE (10 440, 89% female) and SSc (2277, 88% female), (median age of 64/47/54/53/59 years at study entry, respectively), under prescribed treatment between 2015 and 2019, were extracted from the electronic database covering nearly 99% of the Greek population. RESULTS: After 1:5 (patients:general population) matching for gender/age, we found that survival was worse in SSc, followed by SLE and inflammatory arthritis. Compared with the general population HRs for death increased from the first 3 years to 5 years of observation possibly due to increases in disease duration: RA (from 0.63 to 1.13 (95% CI: 1.05 to 1.22), AS (from 0.62 to 1.01, (95% CI: 0.76 to 1.33)), PsA (from 0.68 to 1.06, (95% CI: 0.88 to 1.28)), SLE (from 1.52 to 1.98, (95% CI: 1.67 to 2.33)) and SSc (from 2.27 to 4.24, (95% CI: 3.19 to 5.63)). In both SLE and SSc mortality was increased in men than women and in patients younger than 50 years. CONCLUSIONS: Survival rates over 5 years in inflammatory arthritis under treatment are currently becoming comparable (AS/PsA) or slightly higher (RA) than those of the general population. However, all-cause mortality is almost twofold and fourfold higher in SLE and SSc, respectively, being even higher for male and younger patients.

Does Sodium Intake Induce Systemic Inflammatory Response? A Systematic Review and Meta-Analysis of Randomized Studies in Humans

Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect of high versus low sodium dose (HSD vs. LSD), as defined per study, on plasma circulating inflammatory biomarkers. Eight RCTs that examined CRP, TNF-a and IL-6 were found. Meta-analysis testing the change of each biomarker in HSD versus LSD was possible for CRP (n = 5 studies), TNF-a (n = 4 studies) and IL-6 (n = 4 studies). The pooled difference (95% confidence intervals) per biomarker was for: CRP values of 0.1(-0.3, 0.4) mg/L; TNF-a -0.7(-5.0, 3.6) pg/mL; IL-6 -1.1(-3.3 to 1.1) pg/mL. Importantly, there was inconsistency between RCTs regarding major population characteristics and the applied methodology, including a very wide range of LSD (460 to 6740 mg/day) and HSD (2800 to 7452 mg/day). Although our results suggest that the different levels of daily sodium intake are not associated with significant changes in the level of systemic inflammation in humans, this outcome may result from methodological issues. Based on these identified methodological issues we propose that future RCTs should focus on young healthy participants to avoid confounding effects of comorbidities, should have three instead of two arms (very low, "normal" and high) of daily sodium intake with more than 100 participants per arm, whereas an intervention duration of 14 days is adequate.

Further Guidance in Implementing the Standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score.

The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score was developed to establish a simple, standardized scoring system for researchers to quantify adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations and assess its impact on cancer risk and other health-related outcomes. The aim of this commentary is to clarify potential points of ambiguity in its application, focusing on aspects related to specific subscore components (physical activity, fast foods, alcohol, and sugar-sweetened drinks), how to address different data needs due to varied data collection instruments, and future exploratory score approaches. Overall, we encourage researchers to utilize the standardized score to enhance comparability across populations and countries. Researchers who may adapt or augment the 2018 WCRF/AICR Score are strongly encouraged to provide detailed descriptions of their methods to promote transparency and reproducibility.

Operationalizing the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations: A Standardized Scoring System.

BACKGROUND: Following the publication of the 2018 World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) Third Expert Report, a collaborative group was formed to develop a standardized scoring system and provide guidance for research applications. METHODS: The 2018 WCRF/AICR Cancer Prevention Recommendations, goals, and statements of advice were examined to define components of the new Score. Cut-points for scoring were based on quantitative guidance in the 2018 Recommendations and other guidelines, past research that operationalized 2007 WCRF/AICR Recommendations, and advice from the Continuous Update Project Expert Panel. RESULTS: Eight of the ten 2018 WCRF/AICR Recommendations concerning weight, physical activity, diet, and breastfeeding (optional), were selected for inclusion. Each component is worth one point: 1, 0.5, and 0 points for fully, partially, and not meeting each recommendation, respectively (Score: 0 to 7-8 points). Two recommendations on dietary supplement use and for cancer survivors are not included due to operational redundancy. Additional guidance stresses the importance of accounting for other risk factors (e.g., smoking) in relevant models. CONCLUSIONS: The proposed 2018 WCRF/AICR Score is a practical tool for researchers to examine how adherence to the 2018 WCRF/AICR Recommendations relates to cancer risk and mortality in various adult populations.

Dietary, lifestyle and clinicopathological factors associated with APC mutations and promoter methylation in colorectal cancers from the EPIC-Norfolk study.

The tumour suppressor APC is the most commonly altered gene in colorectal cancer (CRC). Genetic and epigenetic alterations of APC may therefore be associated with dietary and lifestyle risk factors for CRC. Analysis of APC mutations in the extended mutation cluster region (codons 1276-1556) and APC promoter 1A methylation was performed on 185 archival CRC samples collected from participants of the European Prospective Investigation into Cancer (EPIC)-Norfolk study, with the aim of relating these to high-quality seven-day dietary and lifestyle data collected prospectively. Truncating APC mutations (APC(+) ) and promoter 1A methylation (PM(+) ) were identified in 43% and 23% of CRCs analysed, respectively. Distal CRCs were more likely than proximal CRCs to be APC(+) or PM(+) (p = 0.04). APC(+) CRCs were more likely to be moderately/well differentiated and microsatellite stable than APC(-) CRCs (p = 0.05 and 0.03). APC(+) CRC cases consumed more alcohol than their counterparts (p = 0.01) and PM(+) CRC cases consumed lower levels of folate and fibre (p = 0.01 and 0.004). APC(+) or PM(+) CRC cases consumed higher levels of processed meat and iron from red meat and red meat products (p = 0.007 and 0.006). Specifically, CRC cases harbouring GC-to-AT transition mutations consumed higher levels of processed meat (35 versus 24 g/day, p = 0.04) and iron from red meat and red meat products (0.8 versus 0.6 mg/day, p = 0.05). In a logistic regression model adjusted for age, sex and cigarette-smoking status, each 19 g/day (1SD) increment increase in processed meat consumption was associated with cases with GC-to-AT mutations (OR 1.68, 95% CI 1.03-2.75). In conclusion, APC(+) and PM(+) CRCs may be influenced by diet and GC-to-AT mutations in APC are associated with processed meat consumption, suggesting a mechanistic link with dietary alkylating agents, such as N-nitroso compounds.

MLH1 promoter methylation, diet, and lifestyle factors in mismatch repair deficient colorectal cancer patients from EPIC-Norfolk.

There is conflicting evidence for the role diet and lifestyle play in the development of mismatch repair (MMR)-deficient colorectal cancers (CRC). In this study, associations between MMR deficiency, clinicopathological characteristics, and dietary and lifestyle factors in sporadic CRC were investigated. Tumor samples from 185 individuals in the EPIC-Norfolk study were analyzed for MLH1 gene promoter methylation and microsatellite instability (MSI). Dietary and lifestyle data were collected prospectively using 7-day food diaries (7dd) and questionnaires. MMR-deficient tumor cases (MLH1 promoter methylation positive, MSI-H) were more likely to be female, older at diagnosis, early Dukes' stage (A/B), and proximal in location (MSI-H P = 0.03, 0.03, 0.02, and 0.001, respectively). Tumors with positive MLH1 promoter methylation (>20%) were associated with poor differentiation (P = 0.03). Low physical activity was associated with cases without MSI (P = 0.05). MMR deficiency was not significantly associated with cigarette smoking or alcohol, folate, fruit, vegetable, or meat consumption. We conclude that MMR-deficient tumors represent a distinct subset of sporadic CRC that are proximal in location, early Dukes' stage, and poorly differentiated, in cases that are female and older at diagnosis. There is no overall role for diet and lifestyle in MMR status in CRC, consistent with age-related susceptibility to MLH1 promoter methylation.

Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors.

BACKGROUND: The PTEN tumour suppressor gene and PIK3CA proto-oncogene encode proteins which contribute to regulation and propagation of signal transduction through the PI3K/AKT signalling pathway. This study investigates the prevalence of loss of PTEN expression and mutations in both PTEN and PIK3CA in colorectal cancers (CRC) and their associations with tumour clinicopathological features, lifestyle factors and dietary consumptions. METHODS: 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for PTEN and PIK3CA mutations by DNA sequencing and PTEN expression changes by immunohistochemistry. Dietary and lifestyle data were collected prospectively using seven day food diaries and lifestyle questionnaires. RESULTS: Mutations in exons 7 and 8 of PTEN were observed in 2.2% of CRC and PTEN loss of expression was identified in 34.9% CRC. Negative PTEN expression was associated with lower blood low-density lipoprotein concentrations (p = 0.05). PIK3CA mutations were observed in 7% of cancers and were more frequent in CRCs in females (p = 0.04). Analysis of dietary intakes demonstrated no link between PTEN expression status and any specific dietary factor. PTEN expression negative, proximal CRC were of more advanced Dukes' stage (p = 0.02) and poor differentiation (p < 0.01). Testing of the prevalence of PIK3CA mutations and loss of PTEN expression demonstrated that these two events were independent (p = 0.55). CONCLUSION: These data demonstrated the frequent occurrence (34.9%) of PTEN loss of expression in colorectal cancers, for which gene mutations do not appear to be the main cause. Furthermore, dietary factors are not associated with loss of PTEN expression. PTEN expression negative CRC were not homogenous, as proximal cancers were associated with a more advanced Dukes' stage and poor differentiation, whereas distal cancers were associated with earlier Dukes' stage.