This analysis of Norwegian registry data suggests that colonoscopic surveillance during the 8 years after removal of low-risk adenomas is not required for a reduction in colorectal-cancer mortality.
...Screening programs for colorectal cancer are currently implemented in many Western populations
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because randomized trials have documented an association between screening and a sustained reduction in colorectal-cancer mortality.
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The benefit is most likely due to early detection of cancer, endoscopic removal of adenomas, and surveillance of patients who are considered to be at high risk for the development of new neoplastic lesions.
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However, precise quantification of the risk of death from cancer after adenoma removal has been hampered by the scarceness of large, population-based studies with long follow-up periods.
Previous studies were performed in populations undergoing intensive surveillance, . . .
To examine the association between low-dose aspirin use and risk of colorectal cancer (CRC).
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.
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.
In this nationwide cohort, use of low-dose aspirin was associated with a lower risk of CRC.
Multiple epigenetic and genetic changes have been reported in colorectal tumors, but few of these have clinical impact. This study aims to pinpoint epigenetic markers that can discriminate between ...non-malignant and malignant tissue from the large bowel, i.e. markers with diagnostic potential. The methylation status of eleven genes (ADAMTS1, CDKN2A, CRABP1, HOXA9, MAL, MGMT, MLH1, NR3C1, PTEN, RUNX3, and SCGB3A1) was determined in 154 tissue samples including normal mucosa, adenomas, and carcinomas of the colorectum. The gene-specific and widespread methylation status among the carcinomas was related to patient gender and age, and microsatellite instability status. Possible CIMP tumors were identified by comparing the methylation profile with microsatellite instability (MSI), BRAF-, KRAS-, and TP53 mutation status.
The mean number of methylated genes per sample was 0.4 in normal colon mucosa from tumor-free individuals, 1.2 in mucosa from cancerous bowels, 2.2 in adenomas, and 3.9 in carcinomas. Widespread methylation was found in both adenomas and carcinomas. The promoters of ADAMTS1, MAL, and MGMT were frequently methylated in benign samples as well as in malignant tumors, independent of microsatellite instability. In contrast, normal mucosa samples taken from bowels without tumor were rarely methylated for the same genes. Hypermethylated CRABP1, MLH1, NR3C1, RUNX3, and SCGB3A1 were shown to be identifiers of carcinomas with microsatellite instability. In agreement with the CIMP concept, MSI and mutated BRAF were associated with samples harboring hypermethylation of several target genes.
Methylated ADAMTS1, MGMT, and MAL are suitable as markers for early tumor detection.
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.
...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.
Diversity and composition analyses showed no significant differences between CRC, HRA, and healthy controls.
was more abundant in CRC compared with healthy controls in both the 16S and metagenome data. The abundance of
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spp. was associated with time to CRC diagnosis.
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.
Fecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers. Colorectal cancer (CRC) screening based on the fecal ...immunochemical test (FIT) is an effective tool for prevention of cancer development. However, due to the poor sensitivity of FIT especially for premalignant lesions, there is a need for implementation of complementary tests. Improving the identification of individuals who would benefit from further investigation with colonoscopy using molecular analysis, such as miRNA profiling of FIT samples, would be ideal due to their widespread use. In the present study, we assessed the feasibility of applying small RNA sequencing to measure human miRNAs in FIT leftover buffer in samples from two European screening populations. We showed robust detection of miRNAs with profiles similar to those obtained from specimens sampled using the established protocol of RNA stabilizing buffers, or in long-term archived samples. Detected miRNAs exhibited differential abundances for CRC, advanced adenoma, and control samples that were consistent for FIT and RNA-stabilizing buffers. Interestingly, the sequencing data also allowed for concomitant evaluation of small RNA-based microbial profiles. We demonstrated that it is possible to explore the human miRNome in FIT leftover samples across populations and envision that the analysis of small RNA biomarkers can complement the FIT in large scale screening settings.
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 (
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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.
The possible protective effect of aspirin on risk of colorectal cancer (CRC) is still highly debated.
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).
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.
Our results suggest that long-term use of aspirin might have a protective effect against adenomas and colorectal cancer, but not ASLs.
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.
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).
Altogether 721 (24%) individuals were categorized as inconsistent participants Current smoking and BMI ≥30 kg/m
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).
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.
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