Exploring the gut DNA virome in fecal immunochemical test stool samples reveals associations with lifestyle in a large population-based study.

Stool samples for fecal immunochemical tests (FIT) are collected in large numbers worldwide as part of colorectal cancer screening programs. Employing FIT samples from 1034 CRCbiome participants, recruited from a Norwegian colorectal cancer screening study, we identify, annotate and characterize more than 18000 DNA viruses, using shotgun metagenome sequencing. Only six percent of them are assigned to a known taxonomic family, with Microviridae being the most prevalent viral family. Linking individual profiles to comprehensive lifestyle and demographic data shows 17/25 of the variables to be associated with the gut virome. Physical activity, smoking, and dietary fiber consumption exhibit strong and consistent associations with both diversity and relative abundance of individual viruses, as well as with enrichment for auxiliary metabolic genes. We demonstrate the suitability of FIT samples for virome analysis, opening an opportunity for large-scale studies of this enigmatic part of the gut microbiome. The diverse viral populations and their connections to the individual lifestyle uncovered herein paves the way for further exploration of the role of the gut virome in health and disease.

Lifestyle changes in middle age and risk of cancer: evidence from the European Prospective Investigation into Cancer and Nutrition.

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers-including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others-using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95-0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07-1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65-0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.

Lower participation among immigrants in colorectal cancer screening in Norway.

Introduction: Organized cancer screening programs should be equally accessible for all groups in society. We assessed differences in participation in colorectal cancer (CRC) screening among different immigrant groups. Methods: Between 2012 and 2019, 140,000 individuals aged 50 to 74 years were randomly invited to sigmoidoscopy or repeated faecal immunochemical test (FIT) in a CRC screening trial. In this study, we included 46,919 individuals invited to sigmoidoscopy and 70,018 invited to the first round of FIT between 2012 and 2017. We examined difference in participation between non-immigrants and immigrants, and within different immigrant groups by geographic area of origin, using logistic regression models, adjusted for several sociodemographic factors and health factors. Results: In total, we included 106,695 non-immigrants and 10,242 immigrants. The participation rate for FIT was 60% among non-immigrants, 58% among immigrants from Western countries and 37% among immigrants from non-Western countries. The participation rate for sigmoidoscopy was 53% among non-immigrants, 48% among immigrants from Western countries and 23% among immigrants from non-Western countries. Compared to non-immigrants, multivariate adjusted odds ratio for non-participation in FIT screening was 1.13 (95% confidence interval 1.04-1.23) and 1.82 (1.69-1.96) for immigrants from Western and non-Western countries. The corresponding numbers in sigmoidoscopy screening were 1.34 (1.21-1.48) and 2.83 (2.55-3.14). The lowest participation was observed in immigrants from Eastern Europe, Northern Africa and Western Asia, and South-Central Asia. Conclusion: Participation in CRC screening in Norway was particularly low among non-Western immigrants, which could put them at increased risk for late stage diagnosis of CRC. Participation was lower in sigmoidoscopy screening than in FIT screening, especially among immigrants from non-Western countries.

Effect of invitation letter in language of origin on screening attendance: randomised controlled trial in BreastScreen Norway.

OBJECTIVE: To explore attendance at organised mammographic screening among immigrant groups that received an invitation letter and information leaflet (invitation) in their language of origin and Norwegian compared with Norwegian only. DESIGN: Randomised controlled trial. SETTING: Population based screening programme for breast cancer in Norway (BreastScreen Norway), which invites women aged 50-69 to two-view mammographic screening biennially. PARTICIPANTS: All women invited to BreastScreen Norway in the study period April 2021 to June 2022 whose language of origin was Arabic (women born in Algeria, Egypt, Lebanon, Iraq, Palestine, Sudan, Syria, Tunisia, or Morocco), English (women born in the Philippines), Polish (women born in Poland), Somali (women born in Somalia), or Urdu (women born in Pakistan) (n=11 347). INTERVENTION: The study group received an invitation to screening in their language of origin and in Norwegian, whereas the control group received an invitation in Norwegian only during the study period. MAIN OUTCOME MEASURE: Attendance at BreastScreen Norway during the study period. RESULTS: Overall attendance was 46.5% (2642/5683) in the study group and 47.4% (2682/5664) in the control group. No statistical differences in attendance were observed after stratification by language of invitation, age at invitation, or years since immigration. CONCLUSIONS: No difference in attendance was observed between immigrant women invited to BreastScreen Norway in their language of origin and in Norwegian compared with Norwegian only. Several barriers to cancer screening may exist among immigrants, and translating the invitation is probably only a part of a complex explanation. TRIAL REGISTRATION: NCT04672265. CLINICALTRIALS: gov NCT04672265.

Development and validation of a risk prediction model for post-polypectomy colorectal cancer in the USA: a prospective cohort study.

Background: Effective risk stratification tools for post-polypectomy colorectal cancer (PPCRC) are lacking. We aimed to develop an effective risk stratification tool for the prediction of PPCRC in three large population-based cohorts and to validate the tool in a clinical cohort. Methods: Leveraging the integrated endoscopic, histopathologic and epidemiologic data in three U.S population-based cohorts of health professional (the Nurses' Health Study (NHS) I, II and Health Professionals Follow-up Study (HPFS)), we developed a risk score to predict incident PPCRC among 26,741 patients with a polypectomy between 1986 and 2017. We validated the PPCRC score in the Mass General Brigham (MGB) Colonoscopy Cohort (Boston, Massachusetts, U.S) of 76,603 patients with a polypectomy between 2007 and 2018. In all four cohorts, we collected detailed data on patients' demographics, endoscopic history, polyp features, and lifestyle factors at polypectomy. The outcome, incidence of PPCRC, was assessed by biennial follow-up questionnaires in the NHS/HPFS cohorts, and through linkage to the Massachusetts Cancer Registry in the MGB cohort. In all four cohorts, individuals who were diagnosed with CRC or died before baseline or within six months after baseline were excluded. We used Cox regression to calculate the hazard ratio (HR), 95% confidence interval (CI) and assessed the discrimination using C-statistics and reclassification using the Net Reclassification Improvement (NRI). Findings: During a median follow-up of 12.8 years (interquartile range (IQR): 9.3, 16.7) and 5.1 years (IQR: 2.7, 7.8) in the NHS/HPFS and MGB cohorts, we documented 220 and 241 PPCRC cases, respectively. We identified a PPCRC risk score based on 11 predictors. In the validation cohort, the PPCRC risk score showed a strong association with PPCRC risk (HR for high vs. low, 3.55, 95% CI, 2.59-4.88) and demonstrated a C-statistic (95% CI) of 0.75 (0.70-0.79), and was discriminatory even within the low- and high-risk polyp groups (C-statistic, 0.73 and 0.71, respectively) defined by the current colonoscopy surveillance recommendations, leading to a NRI of 45% (95% CI, 36-54%) for patients with PPCRC. Interpretation: We developed and validated a risk stratification model for PPCRC that may be useful to guide tailored colonoscopy surveillance. Further work is needed to determine the optimal surveillance interval and test the added value of other predictors of PPCRC beyond those included in the current study, along with implementation studies. Funding: US National Institutes of Health, the American Cancer Society, the South-Eastern Norway Regional Health Authority, the Deutsche Forschungsgemeinschaft.

Long-term follow-up of colorectal cancer screening attendees identifies differences in Phascolarctobacterium spp. using 16S rRNA and metagenome sequencing.

Background: The microbiome has been implicated in the initiation and progression of colorectal cancer (CRC) in cross-sectional studies. However, there is a lack of studies using prospectively collected samples. Methods: From the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, we analyzed 144 archived fecal samples from participants who were diagnosed with CRC or high-risk adenoma (HRA) at screening and from participants who remained cancer-free during 17 years of follow-up. We performed 16S rRNA sequencing of all the samples and metagenome sequencing on a subset of 47 samples. Differences in taxonomy and gene content between outcome groups were assessed for alpha and beta diversity and differential abundance. Results: Diversity and composition analyses showed no significant differences between CRC, HRA, and healthy controls. Phascolarctobacterium succinatutens was more abundant in CRC compared with healthy controls in both the 16S and metagenome data. The abundance of Bifidobacterium and Lachnospiraceae spp. was associated with time to CRC diagnosis. Conclusion: Using a longitudinal study design, we identified three taxa as being potentially associated with CRC. These should be the focus of further studies of microbial changes occurring prior to CRC diagnosis.

Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations with stages of colorectal carcinogenesis.

BACKGROUND: While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients. METHODS: Adherence to the seven-point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected lesions. RESULTS: Of 1486 screening participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively. CONCLUSIONS: Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen-detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions.

Use of surveillance colonoscopy among individuals with removal of high-risk polyps according to the US Multi-Society Task Force recommendations.

BACKGROUND: Individuals with colorectal polypectomy are recommended to undergo surveillance colonoscopies at certain intervals to prevent subsequent colorectal cancer. Use of postpolypectomy surveillance according to the 2006 US Multi-Society Task Force (USMSTF) recommendations in an integrated health care system was investigated. METHODS: Use of surveillance colonoscopies was prospectively assessed among 3691 patients with removal of high-risk polyps at a screening colonoscopy during 2007-2012 in the Mass General Brigham Colonoscopy Cohort. With the follow-up up to 2017, the compliance with, overuse, and underuse of postpolypectomy surveillance according to the 2006 USMSTF recommendations was assessed. Surveillance use according to demographic factors was also investigated. RESULTS: During a median follow-up of 4.4 years (5th percentile, 95th percentile, 1.0, 9.9) 2360 (64%) patients had undergone a surveillance colonoscopy, among whom 758 (21%) were considered compliant with the USMSTF recommendations. A substantial underuse of surveillance colonoscopies of 62% was observed. Older age and lower income were associated with a higher incidence of underuse, whereas having a family history of colorectal cancer were associated with lower incidence of underuse. Overuse of surveillance colonoscopies was present in 17% of patients but showed no significant associations with demographic factors. CONCLUSION: Substantial underuse of surveillance in patients with high-risk polyps was observed, particularly those with low income and older age. Efforts are needed to improve delivery and use of surveillance colonoscopy. PLAIN LANGUAGE SUMMARY: The US Multi-Society Task Force recommends follow-up surveillance colonoscopy after polyp removal in the bowel, with intervals depending on the most severe findings. Adherence to surveillance recommendations in a large study with up to 10 years of follow-up among patients with high-risk polyps was investigated. Only 21% of patients adhered to the surveillance recommendations, whereas 62% showed delayed or no use of surveillance. Findings highlight the need for improved use of surveillance colonoscopy among patients at high risk of colorectal cancer.

Type and Severity of Mental Illness and Participation in Colorectal Cancer Screening.

INTRODUCTION: The effectiveness of colorectal cancer screening programs depends on the participation rate. This study examined the association between type and severity of mental illness and colorectal cancer screening participation. METHODS: Between 2012 and 2017, a total of 46,919 individuals were invited to sigmoidoscopy screening in Norway, and 70,019 were invited to fecal immunochemical testing. In 2022, logistic regression was used to evaluate the association between the use of antipsychotics, anxiolytics, hypnotics, and antidepressants in the year preceding the screening invitation and screening participation, adjusted for demographic and socioeconomic factors. Defined daily doses of individual drugs were used to assess dose‒response relationships. RESULTS: Overall, 19.2% (24.8% of women, 13.4% of men) of all invitees used at least 1 psychotropic medication. Nonparticipation in the 2 arms combined was associated with the use of anxiolytics (60.7% in users vs 43.2% in nonusers; OR=1.53; 95% CI=1.45, 1.62) and antipsychotics (64.3% vs 43.8%; OR=1.41; 95% CI=1.30, 1.53) and increased with higher doses for both drugs. Hypnotics and antidepressants were only weakly associated with nonparticipation in higher doses. Participation rates were 57.3%, 52.3%, 42.9%, and 35.4% in those prescribed 0, 1, 2, and 3-4 classes of psychotropic medications, respectively. The associations between the use of psychotropic medications and nonparticipation were similar for the 2 screening tests. CONCLUSIONS: These findings show significant disparities in colorectal cancer screening participation for individuals with mental illness, independent of the screening method. Moreover, screening participation varied depending on the type and severity of mental illness. Targeted interventions are warranted to ensure that people with mental illness are supported to access the benefits of colorectal cancer screening.

Changes in Lifestyle and Risk of Colorectal Cancer in the European Prospective Investigation Into Cancer and Nutrition.

INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort. METHODS: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

Polish immigrants' access to colorectal cancer screening in Norway - a qualitative study.

BACKGROUND: The Norwegian colorectal cancer (CRC) screening programme started in May 2022. Inequities in uptake of CRC screening is a concern, and we expect that immigrants are at risk of non-uptake. Immigrants from Poland are the most populous immigrant group in Norway. The purpose of this study was to identify and explore factors that may facilitate Polish immigrants' access to the Norwegian CRC screening programme. MATERIAL AND METHODS: This study was based on qualitative interviews with ten Polish immigrants in Norway. The participants represented a convenience sample that varied in terms of gender, education, employment, time in Norway, place of residence, Norwegian language skills and ties to the Norwegian-Polish community. We performed thematic content analysis to understand CRC screening from the perspective of Polish immigrants, using transnationalism and Levesque's conceptualization of accessibility as theoretical frameworks. RESULTS: We grouped our findings into three themes; "understanding of CRC development and the need to access health care", "binationalism" and "improving accessibility through information". Within these themes, various factors influenced the participants' accessibility to CRC screening, namely knowledge about the screening and about causes, development and prevention of the disease, language, choice of screening country, trust in health personnel's competence, information needs, methods and sources, as well as participants' perception of the faecal immunochemical test screening user manual. These factors were further influenced by communication between the Polish community in Norway and Poland, as well as travel between the countries. CONCLUSION: We identified several factors that can be targeted with an aim to increase Polish immigrants' access to the Norwegian CRC screening programme. Effective measures could include increasing cultural competence among health care providers and providing information in Polish through Polish-speaking health care professionals, general practitioners and internet portals used by the Polish-speaking community. Focusing on accessibility in a transnational setting, our findings may be of interest for policy makers and service providers planning preventive health measures for immigrants.

The impact of driving time on participation in colorectal cancer screening with sigmoidoscopy and faecal immunochemical blood test.

BACKGROUND: High participation rates are important for a colorectal cancer (CRC) screening programme to be effective. Having a long travelling distance to screening centres may impede participation. METHODS: We analysed the association between driving time from home address to screening centre and participation among individuals invited to screening with faecal immunochemical test (FIT) (n = 68,624) or sigmoidoscopy (n = 46,076) in a randomized trial in Norway in 2012-17. Two screening centres were involved. We fitted multiple logistic regression models, adjusted for demographic, socioeconomic and health characteristics, and reported odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Participation rates were 58.9 % (n = 40,445) for FIT and 51.9 % (n = 23,911) for sigmoidoscopy. In sigmoidoscopy, participation was 56.9 % and 47.9 % in those living < 20 and > 60 min by car from the screening centres, respectively. For each 10 min driving time increase, OR for participating in sigmoidoscopy screening was 0.93 (95 % CI 0.91-0.95). There was a significant difference between the two screening centres (p-value for heterogeneity <0.001). Participation in FIT screening were 61.2 % and 57.1 % in those with < 20 and > 60 min driving time, respectively, and the OR was 0.98 (95 % CI 0.96-0.99) for each 10 min increase (heterogeneity between screening methods, P-value <0.001). Among those with a positive FIT, compliance to colonoscopy was higher in those living < 20 compared to > 60 min from the centres (95.1 % vs. 92.9 %, respectively, OR 0.86; 95 % CI 0.77-0.93 for each 10 min increase). CONCLUSIONS: Driving time to screening centre was a significant predictor of participation, mainly in sigmoidoscopy. There were local differences in the impact of driving time on participation. Driving time also affected compliance to colonoscopy after a positive FIT. When planning a CRC screening programme, one should consider offering people living far from screening sites special assistance to facilitate their participation.

Associations of red and processed meat intake with screen-detected colorectal lesions.

Limited data exist regarding the role of meat consumption in early-stage colorectal carcinogenesis. We examined associations of red and processed meat intake with screen-detected colorectal lesions in immunochemical fecal occult blood test (FIT)-positive participants, enrolled in the Norwegian CRCbiome study during 2017-2021, aged 55-77 years. Absolute and energy-adjusted intakes of red and processed meat (combined and individually) were assessed using a validated, semi-quantitative FFQ. Associations between meat intake and screen-detected colorectal lesions were examined using multinomial logistic regression analyses with adjustment for key covariates. Of 1162 participants, 319 presented with advanced colorectal lesions at colonoscopy. High v. low energy-adjusted intakes of red and processed meat combined, as well as red meat alone, were borderline to significantly positively associated with advanced colorectal lesions (OR of 1·24 (95 % CI 0·98, 1·57) and 1·34 (95 % CI 1·07, 1·69), respectively). A significant dose-response relationship was also observed for absolute intake levels (OR of 1·32 (95 % CI 1·09, 1·60) per 100 g/d increase in red and processed meat). For processed meat, no association was observed between energy-adjusted intakes and advanced colorectal lesions. A significant positive association was, however, observed for participants with absolute intake levels ≥ 100 v. < 50 g/d (OR of 1·19 (95 % CI 1·09, 1·31)). In summary, high intakes of red and processed meat were associated with presence of advanced colorectal lesions at colonoscopy in FIT-positive participants. The study demonstrates a potential role of dietary data to improve the performance of FIT-based screening.

Characteristics of nonparticipants in a randomised colorectal cancer screening trial comparing sigmoidoscopy and faecal immunochemical testing.

Public health systems should guarantee universal access to health care services, including cancer screening. We assessed whether certain population subgroups were underrepresented among participants in colorectal cancer screening with sigmoidoscopy and faecal immunochemical testing (FIT). Between 2012 and 2019, about 140 000 individuals aged 50 to 74 years were randomly invited to once-only sigmoidoscopy or first round of FIT screening. Our study included 46 919 individuals invited to sigmoidoscopy and 70 019 to FIT between 2012 and 2017. We used logistic regression models to evaluate if demographic and socioeconomic factors and use of certain drugs were associated with participation. Twenty-four thousand one hundred and fifty-nine (51.5%) individuals attended sigmoidoscopy and 40 931 (58.5%) FIT screening. Male gender, young age, low education and income, being retired or unemployed, living alone, being an immigrant, long driving time to screening centre, and use of antidiabetic and psychotropic drugs were associated with low participation in both screening groups. Many of these factors also predicted low acceptance of colonoscopy after positive FIT. While male gender, young age and living alone were more strongly associated with nonparticipation in FIT than sigmoidoscopy, low education and income, being retired or immigrant and long driving time were more strongly associated with nonparticipation in sigmoidoscopy than FIT. In conclusion, participation was lower in sigmoidoscopy than FIT. Predictors of nonparticipation were similar between arms. However, low socioeconomic status, being an immigrant and long driving time affected participation more in sigmoidoscopy screening, suggesting that FIT may guarantee more equal access to screening services than sigmoidoscopy.

Lifestyle predictors for inconsistent participation to fecal based colorectal cancer screening.

BACKGROUND: Consistent participation in colorectal cancer (CRC) screening with repeated fecal immunochemical test (FIT) is important for the success of the screening program. We investigated whether lifestyle risk factors for CRC were related to inconsistent participation in up to four rounds of FIT-screening. METHOD: We included data from 3,051 individuals who participated in up to four FIT-screening rounds and returned a lifestyle questionnaire. Using logistic regression analyses, we estimated associations between smoking habits, body mass index (BMI), physical activity, alcohol consumption, diet and a healthy lifestyle score (from least favorable 0 to most favorable 5), and inconsistent participation (i.e. not participating in all rounds of eligible FIT screening invitations). RESULTS: Altogether 721 (24%) individuals were categorized as inconsistent participants Current smoking and BMI ≥30 kg/m2 were associated with inconsistent participation; odds ratios (ORs) and 95% confidence intervals (CIs) were 1.54 (1.21-2.95) and 1.54 (1.20-1.97), respectively. A significant trend towards inconsistent participation by a lower healthy lifestyle score was observed (p < 0.05). CONCLUSIONS: Lifestyle behaviors were associated with inconsistent participation in FIT-screening. Initiatives aimed at increasing participation rates among those with the unhealthiest lifestyle have a potential to improve the efficiency of screening.

The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants.

BACKGROUND: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. METHODS: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. DISCUSSION: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01538550 .

Lifestyle changes and risk of cancer: experience from the Swedish women's lifestyle and health cohort study.

BACKGROUND: The impact of lifestyle changes on cancer risk is yet to be elucidated. We investigated this issue in the Swedish Women's Lifestyle and Health Cohort Study. MATERIAL AND METHODS: We measured changes by comparing two questionnaires, filled in 1991/92 and 2003. We followed women for cancer from 2003 until 2012. We used Cox regression models to assess the effect of changes in smoking, alcohol consumption, body mass index (BMI), physical activity and a lifestyle score on the risk of lifestyle-related cancer. One point was added to the lifestyle score for each of these: non-smoking, alcohol consumption ≤12 grams/day, BMI <25 kg/m2 and high level of physical activity. RESULTS: We included 29,930 women. From 1991/92 to 2003, median age changed from 40.0 to 51.7 years, alcohol consumption from 2.5 to 4.7 grams/day, BMI from 22.7 to 24.5 kg/m2, proportion of current smokers from 31.0 to 20.6% and women reporting high physical activity from 27.2 to 37.0%. Women who quit smoking had lower risk of smoking-related cancers compared to women who continued (hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.55-1.00). Women who reduced their weight by more than 5%, compared to women with stable weight, had lower risk of breast cancer (HR 0.49, 95% CI 0.31-0.78). Among women with score of 0-2 in 1992/93, those who improved to 3-4 had lower risk of lifestyle-related cancers compared to women who did not (HR 0.81, 95% CI 0.66-0.99). CONCLUSIONS: Healthy lifestyle changes, particularly smoking cessation and weight reduction, were associated with a decreased risk of cancer.

Public Awareness and Perceptions of Colorectal Cancer Prevention: a Cross-Sectional Survey.

We aimed to investigate awareness of colorectal cancer (CRC) lifestyle risk factors, willingness to participate in CRC screening, and preferences concerning channels for information on CRC prevention in the general population, including the target age of the upcoming Norwegian national CRC screening program. The present study was a cross-sectional online survey of adults aged 39 to 55 years registered as Kantar Web Panel respondents in Norway. The survey included demographic characteristics, multiple choice knowledge questions of lifestyle risk factors for CRC, attitudes towards CRC screening, and preferred channels for receiving information on CRC prevention. Of 4375 participants invited, 2007 (46%) answered the survey. The average number of correctly identified lifestyle risk factors for CRC was 7.3 of ten. Women were significantly more likely than men, and those with university or college education more likely than those with lower education to correctly identify at least eight risk factors (odds ratio, OR = 1.53, 95% confidence interval, CI 1.25-1.87, and OR = 1.51, 95% CI 1.23-1.86, respectively). The number of correctly identified risk factors was positively associated with willingness to participate in CRC screening (P for trend < 0.001). The national public work force and the Norwegian Cancer Society were selected by 76% and 69% of the participants, respectively, to be trustworthy sources of information on CRC prevention. Awareness of CRC risk factors was associated with willingness to participate in CRC screening. The national public work force and Cancer Society can be generally accepted sources of CRC preventive information.

Association between lifestyle and site-specific advanced colorectal lesions in screening with faecal immunochemical test and sigmoidoscopy.

BACKGROUND: Lifestyle factors may help to identify individuals at high-risk for colorectal cancer (CRC). AIMS: To examine the association between lifestyle, referral for follow-up colonoscopy and proximal neoplasia detection in CRC screening. METHODS: In this observational study, 14,832 individuals aged 50-74 years were invited to faecal immunochemical test (FIT) or sigmoidoscopy screening. Advanced lesions (AL), including advanced adenomas, advanced serrated lesions and CRC were divided according to location: distal-only, or proximal with or without distal AL. We collected information on smoking habit, body mass index and alcohol intake through a questionnaire. RESULTS: Out of 3,318 FIT and 2,988 sigmoidoscopy participants, 516 (16%) and 338 (11%), respectively, were referred for follow-up colonoscopy after a positive screening test. Two-hundred-and-fifty-six (4%) had distal-only and 119 (2%) proximal AL. In FIT participants, obesity and high alcohol intake were associated with proximal AL; odds ratio (95% confidence interval) 2.68 (1.36-5.26) and 2.16 (1.08-4.30), respectively. In sigmoidoscopy participants, current smoking was associated with proximal AL; 4.58 (2.24-9.38), and current smoking and obesity were associated with referral for colonoscopy; 2.80 (2.02-3.89) and 1.42 (1.01-2.00), respectively. CONCLUSION: Current smoking, obesity and high alcohol intake were associated with screen-detected proximal colorectal AL. Current smoking and obesity were associated with referral for follow-up colonoscopy in sigmoidoscopy screening.