Low-Dose Aspirin and Prevention of Colorectal Cancer: Evidence From a Nationwide Registry-Based Cohort in Norway.

INTRODUCTION: To examine the association between low-dose aspirin use and risk of colorectal cancer (CRC). METHODS: In this nationwide cohort study, we identified individuals aged 50 years or older residing for 6 months or more in Norway in 2004-2018 and obtained data from national registers on drug prescriptions, cancer occurrence, and sociodemographic factors. Multivariable Cox regression models were used to estimate the association between low-dose aspirin use and CRC risk. In addition, we calculated the number of CRC potentially averted by low-dose aspirin use. RESULTS: We included 2,186,390 individuals. During the median follow-up of 10.9 years, 579,196 (26.5%) used low-dose aspirin, and 38,577 (1.8%) were diagnosed with CRC. Current use of aspirin vs never use was associated with lower CRC risk (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.84-0.90). The association was more pronounced for metastatic CRC (HR 0.79; 95% CI 0.74-0.84) than regionally advanced (HR 0.89; 95% CI 0.85-0.92) and localized CRC (HR 0.93; 95% CI 0.87-1.00; P heterogeneity = 0.001). A significant trend was found between duration of current use and CRC risk: HR 0.91 (95% CI 0.86-0.95) for <3 years, HR 0.85 (0.80-0.91) for ≥3 and <5 years, and HR 0.84 (0.80-0.88) for ≥5 years of use vs never use ( P trend < 0.001). For past use, HR were 0.89 (95% CI 0.84-0.94) for <3 years, 0.90 (0.83-0.99) for ≥3 and <5 years, and 0.98 (0.91-1.06) for ≥5 years since last use vs never use ( P -trend < 0.001). We estimated that aspirin use averted 1,073 cases of CRC (95% CI 818-1,338) in the study period. DISCUSSION: In this nationwide cohort, use of low-dose aspirin was associated with a lower risk of CRC.

Association between use of low-dose aspirin and detection of colorectal polyps and cancer in a screening setting.

BACKGROUND: The possible protective effect of aspirin on risk of colorectal cancer (CRC) is still highly debated. METHODS: We used data from Bowel Cancer Screening in Norway, a trial randomizing individuals from general population, aged 50-74 years, to flexible sigmoidoscopy or faecal immunochemical test (FIT), to study the association between aspirin use and detection of CRC and two CRC precursors: adenomas and advanced serrated lesions (ASL). Prescriptions of low-dose aspirin were obtained from Norwegian prescription database. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 64,889 screening participants (24,159 sigmoidoscopy, 40,730 FIT), 314 (0.5%) had CRC, 6,208 (9.6%) adenoma and 659 (1.0%) ASL. Overall and short-term use (<3 years) of low-dose aspirin, versus no use, were not associated with any colorectal lesion. Long-term use (≥3 years) was associated with lower detection of CRC (overall OR 0.66, 95%CI 0.46-0.93; sigmoidoscopy: 0.56, 0.33-0.97; FIT: 0.72, 0.45-1.15), adenomas in sigmoidoscopy arm (overall OR 0.95, 95%CI 0.87-1.03; sigmoidoscopy: 0.89, 0.80-0.99; FIT: 1.03, 0.89-1.18), but not ASLs. We did not observe significant differences in the effect of aspirin according to the location of colorectal lesions. CONCLUSION: Our results suggest that long-term use of aspirin might have a protective effect against adenomas and colorectal cancer, but not ASLs.

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.

Impact of time between faecal immunochemical tests in colorectal cancer screening on screening results: A natural experiment.

Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT2 ), according to the faecal haemoglobin concentration (f-Hb) at the initial screening round (FIT1 ), and time between the two screening rounds. 18 522 individuals with negative FIT1 who attended FIT2 were included in this study. 245 AN were detected at FIT2 , of which 34 were CRC. The CRC detection rate at FIT2 for participants with FIT1  = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT1 ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49-6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98-1.79), while the OR was 1.13 (1.02-1.26) for AN. Individuals with FIT1 -value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT1 ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f-Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f-Hb.

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.

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.

Detection of cancers and advanced adenomas in asymptomatic participants in colorectal cancer screening: a cross-sectional study.

OBJECTIVES: To assess detection rates for colorectal cancer (CRC) and advanced adenomas in asymptomatic CRC screening participants and bowel symptoms in association with CRC and advanced adenoma. DESIGN: Cross-sectional study. SETTING: Two screening centres. PARTICIPANTS: 42 554 men and women, aged 50-74 years, participating in a randomised CRC screening trial. 36 059 participants underwent a sigmoidoscopy (and follow-up colonoscopy if positive sigmoidoscopy) and 6495 underwent a colonoscopy after a positive faecal immunochemical test (FIT). PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of asymptomatic participants diagnosed with CRC or advanced adenomas. Prevalence of bowel symptoms (rectal bleeding, change in bowel habits, diarrhoea, constipation, bloating, alternating bowel habits, general symptoms, other bowel symptoms) recorded by the endoscopist and their association with CRC and advanced adenomas. RESULTS: Among sigmoidoscopy participants, 7336 (20.3%) reported at least one symptom. 120 (60%) out of 200 individuals with screen-detected CRC and 1301 (76.5%) out of 1700 with advanced adenoma were asymptomatic. Rectal bleeding was associated with detection of CRC and advanced adenoma (OR 4.3, 95% CI 3.1 to 6.1 and 1.8, 95% CI 1.5 to 2.1, respectively), while change in bowel habits only with CRC detection (OR 3.8, 95% CI 2.4 to 6.1). Among the FIT positives, 2173 (33.5%) reported at least one symptom. Out of 299 individuals with screen-detected CRC and 1639 with advanced adenoma, 167 (55.9%) and 1 175 (71.7%) were asymptomatic, respectively. Detection of CRC was associated with rectal bleeding (OR 1.8, 95% CI 1.4 to 2.3), change in bowel habits (OR 2.2, 95% CI 1.4 to 3.5) and abdominal pain (OR 1.8, 95% CI 1.2 to 2.7). CONCLUSIONS: Some bowel symptoms increased the likelihood of being diagnosed with CRC or advanced adenoma. However, the majority of individuals with these findings were asymptomatic. Asymptomatic individuals should be encouraged to participate in CRC screening. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov Identifier: NCT01538550.

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.

Colorectal Cancer Screening With Repeated Fecal Immunochemical Test Versus Sigmoidoscopy: Baseline Results From a Randomized Trial.

BACKGROUND & AIMS: The comparative effectiveness of sigmoidoscopy and fecal immunochemical testing (FIT) for colorectal cancer (CRC) screening is unknown. METHODS: Individuals aged 50-74 years living in Southeast Norway were randomly invited between 2012 and 2019 to either once-only flexible sigmoidoscopy or FIT screening every second year. Colonoscopy was recommended after sigmoidoscopy if any polyp of ≥10 mm, ≥3 adenomas, any advanced adenomas, or CRC was found or, subsequent to, FIT >15 µg hemoglobin/g feces. Data for this report were obtained after complete recruitment in both groups and included 2 full FIT rounds and part of the third round. Outcome measures were participation, neoplasia detection, and adverse events. Age-standardized detection rates and age-adjusted odds ratios (ORs) were calculated. RESULTS: We included 139,291 individuals: 69,195 randomized to sigmoidoscopy and 70,096 to FIT. The participation rate was 52% for sigmoidoscopy, 58% in the first FIT round, and 68% for 3 cumulative FIT rounds. Compared to sigmoidoscopy, the detection rate for CRC was similar in the first FIT round (0.25% vs 0.27%; OR, 0.92; 95% confidence interval [CI], 0.75-1.13) but higher after 3 FIT rounds (0.49% vs 0.27%; OR, 1.87; 95% CI, 1.54-2.27). Advanced adenoma detection rate was lower in the first FIT round compared to sigmoidoscopy at 1.4% vs 2.4% (OR, 0.57; 95% CI, 0.53-0.62) but higher after 3 cumulative FIT rounds at 2.7% vs 2.4% (OR, 1.14; 95% CI, 1.05-1.23). There were 33 (0.05%) serious adverse events in the sigmoidoscopy group compared to 47 (0.07%) in the FIT group (P = .13). CONCLUSIONS: Participation was higher and more CRC and advanced adenomas were detected with repeated FIT compared to sigmoidoscopy. The risk of perforation and bleeding was comparable. Clinicaltrials.gov, Number: NCT01538550.