Association of Polygenic Risk Score and Bacterial Toxins at Screening Colonoscopy with Colorectal Cancer Progression: A Multicenter Case-Control Study.
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SUBMITTER: Piciocchi A
PROVIDER: S-EPMC8402601 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and aimsColorectal cancer (CRC) polygenic risk scores (PRS) may help personalize CRC prevention strategies. We investigated whether an existing PRS was associated with advanced neoplasia (AN) in a population undergoing screening and follow-up colonoscopy.MethodsWe evaluated 10-year outcomes in the Cooperative Studies Program #380 screening colonoscopy cohort, which includes a biorepository of selected individuals with baseline AN (defined as CRC or adenoma ≥10 mm or villous histology, or high-grade dysplasia) and matched individuals without AN. A PRS was constructed from 136 prespecified CRC-risk single nucleotide polymorphisms. Multivariate logistic regression was used to evaluate the PRS for associations with AN prevalence at baseline screening colonoscopy or incident AN in participants with at least one follow-up colonoscopy.ResultsThe PRS was associated with AN risk at baseline screening colonoscopy (P = .004). Participants in the lowest PRS quintile had more than a 70% decreased risk of AN at baseline (odds ratio 0.29, 95% confidence interval 0.14-0.58; P < .001) compared to participants with a PRS in the middle quintile. Using a PRS cut-off of more than the first quintile to indicate need for colonoscopy as primary screening, the sensitivity for detecting AN at baseline is 91.8%. We did not observe a relationship between the PRS and incident AN during follow-up (P = .28).ConclusionA PRS could identify individuals at low risk for prevalent AN. Ongoing work will determine whether this PRS can identify a subset of individuals at sufficiently low risk who could safely delay or be reassured about noninvasive screening. Otherwise, more research is needed to augment these genetic tools to predict incident AN during long-term follow-up.
| S-EPMC11307447 | biostudies-literature
Project description:BackgroundSingle nucleotide polymorphism (SNP)-based polygenic risk scoring is predictive of colorectal cancer (CRC) risk. However, few studies have investigated the association of genetic risk score (GRS) with detection of adenomatous polyps at screening colonoscopy.MethodsWe randomly selected 1769 Caucasian subjects who underwent screening colonoscopy from the Genomic Health Initiative (GHI), a biobank of NorthShore University HealthSystem. Outcomes from initial screening colonoscopy were recorded. Twenty-two CRC risk-associated SNPs were obtained from the Affymetrix™ SNP array and used to calculate an odds ratio (OR)-weighted and population-standardized GRS. Subjects with GRS of < 0.5, 0.5-1.5, and > 1.5 were categorized as low, average and elevated risk.ResultsAmong 1,769 subjects, 520 (29%) had 1 or more adenomatous polyps. GRS was significantly higher in subjects with adenomatous polyps than those without; mean (95% confidence interval) was 1.02 (1.00-1.05) and 0.97 (0.95-0.99), respectively, p < 0.001. The association remained significant after adjusting for age, gender, body mass index, and family history, p < 0.001. The detection rate of adenomatous polyps was 10.8%, 29.0% and 39.7% in subjects with low, average and elevated GRS, respectively, p-trend < 0.001. Higher GRS was also associated with early age diagnosis of adenomatous polyps, p < 0.001. In contrast, positive family history was not associated with risk and age of adenomatous polyps.ConclusionsGRS was significantly associated with adenomatous polyps in subjects undergoing screening colonoscopy. This result may help in stratifying average risk patients and facilitating personalized colonoscopy screening strategies.
| S-EPMC7881602 | biostudies-literature
Project description:Background Different risk-based colorectal cancer (CRC) screening strategies, such as the use of polygenic risk scores (PRS), have been evaluated to improve effectiveness of these programs. However, few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study. Methods A PRS of 133 single nucleotide polymorphisms was assessed for 3619 participants: population controls, screening controls, low-risk lesions (LRL), intermediate-risk (IRL), high-risk (HRL), CRC screening program cases, and clinically diagnosed CRC cases. The PRS was compared between the subset of cases (n = 648; IRL+HRL+CRC) and controls (n = 956; controls+LRL) recruited within a FIT-based screening program. Positive predictive values (PPV), negative predictive values (NPV), and the area under the receiver operating characteristic curve (aROC) were estimated using cross-validation. Results The overall PRS range was 110–156. PRS values increased along the CRC tumorigenesis pathway (Mann-Kendall P value 0.007). Within the screening subset, the PRS ranged 110-151 and was associated with higher risk-lesions and CRC risk (ORD10vsD1 1.92, 95% CI 1.22–3.03). The cross-validated aROC of the PRS for cases and controls was 0.56 (95% CI 0.53–0.59). Discrimination was equal when restricted to positive FIT (aROC 0.56), but lower among negative FIT (aROC 0.55). The overall PPV among positive FIT was 0.48. PPV were dependent on the number of risk alleles for positive FIT (PPVp10-p90 0.48–0.57). Conclusions PRS plays an important role along the CRC tumorigenesis pathway; however, in practice, its utility to stratify the general population or as a second test after a FIT positive result is still doubtful. Currently, PRS is not able to safely stratify the general population since the improvement on PPV values is scarce. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-021-02134-x.
| S-EPMC8574048 | biostudies-literature
Project description:BackgroundThere are limited colonoscopy-based cohort data concerning the effectiveness of colonoscopy in reducing colorectal cancer deaths. The aim of this study was to clarify whether colonoscopy reduces colorectal cancer mortality.MethodsA cohort of 18,816 patients who underwent colonoscopy without a diagnosis of colorectal cancer between 2001 and 2010 at high colonoscopy procedure volume centers was selected. Patient characteristics and colonoscopy findings were assessed. The main endpoint was colorectal cancer death (all, right-sided, and left-sided cancers), and data were censored at the time of the final visit or the final colonoscopy. The standardized all colorectal, colon, and rectal cancer mortality rates were estimated with reference to those of the general Japanese population. Additional outcome was all- cause death and the standardized all-cause mortality rate was also estimated.ResultsThe total observed person-year mortality for colorectal cancer was 67,119. Of these, 4, 3, and 1 patients died from colorectal, colon, and rectal cancers, respectively; these values were significantly lower than the number of expected deaths in the general population, estimated to be 53.1, 34.0, and 19.1, respectively. The standardized mortalities for all colorectal, colon, and rectal cancers were 0.08 (95% confidence interval (CI), 0.02-0.17), 0.09 (95% CI, 0.02-0.22), and 0.05 (95% CI, 0.0002-0.21), respectively. There were 586 all-cause deaths (3.11%) during the observation period. The standardized all-cause mortality ratios were 0.22 (95% CI, 0.206-0.23).ConclusionsThe colorectal cancer mortality of patients who received colonoscopy without colorectal cancer diagnosis decreased significantly compared with that of individuals in the general population. These results were compatible even in patients with right-sided colon cancer.
| S-EPMC5619740 | biostudies-literature
Project description:This study developed a clinical scoring system to predict the risks of PN among screening participants for colorectal cancer. We recruited 5,789 Chinese asymptomatic screening participants who received colonoscopy in Hong Kong (2008-2014). From random sampling of 2,000 participants, the independent risk factors were evaluated for PN using binary regression analysis. The odds ratios for significant risk factors were used to develop a scoring system, with scores stratified into 'average risk' (AR):0-2 and 'high risk' (HR):3-5. The other 3,789 subjects formed an independent validation cohort. Each participant received a score calculated based on their risk factors. The performance of the scoring system was evaluated. The proportion of PN in the derivation and validation cohorts was 12.6% and 12.9%, respectively. Based on age, gender, family history, body mass index and self-reported ischaemic heart disease, 85.0% and 15.0% in the validation cohort were classified as AR and HR, respectively. Their prevalence of PN was 12.0% and 18.1%, respectively. Participants in the HR group had 1.51-fold (95% CI = 1.24-1.84, p < 0.001) higher risk of PN than the AR group. The overall c-statistics of the prediction model was 0.71(0.02). The scoring system is useful in predicting the risk of PN to prioritize patients for colonoscopy.
| S-EPMC4745041 | biostudies-other
Project description:ImportanceRandomized clinical screening trials have shown that sigmoidoscopy screening reduces colorectal cancer (CRC) incidence and mortality. Colonoscopy has largely replaced sigmoidoscopy for CRC screening, but long-term results from randomized trials on colonoscopy screening are still lacking.ObjectiveTo estimate the additional screening benefit of colonoscopy compared with sigmoidoscopy.Design, setting, and participantsThis comparative effectiveness simulation study pooled data on 358 204 men and women randomly assigned to sigmoidoscopy screening or usual care in 4 randomized sigmoidoscopy screening trials conducted in Norway, Italy, the US, and UK with inclusion periods in the years 1993 to 2001. The primary analysis of the study was conducted from January 19 to December 30, 2021.InterventionInvitation to endoscopic screening.Main outcomes and measuresPrimary outcomes were CRC incidence and mortality. Using pooled 15-year follow-up data, colonoscopy screening effectiveness was estimated assuming that the efficacy of colonoscopy in the proximal colon was similar to that observed in the distal colon in the sigmoidoscopy screening trials. The simulation model was validated using data from Norwegian participants in a colonoscopy screening trial.ResultsThis analysis included 358 204 individuals (181 971 women [51%]) aged 55 to 64 years at inclusion with a median follow-up time ranging from 15 to 17 years. Compared with usual care, colonoscopy prevented an estimated 50 (95% CI, 42-58) CRC cases per 100 000 person-years, corresponding to 30% incidence reduction (rate ratio, 0.70 [95% CI, 0.66-0.75]), and prevented an estimated 15 (95% CI, 11-19) CRC deaths per 100 000 person-years, corresponding to 32% mortality reduction (rate ratio, 0.68 [95% CI, 0.61-0.76]). The additional benefit of colonoscopy screening compared with sigmoidoscopy was 12 (95% CI, 10-14) fewer CRC cases and 4 (95% CI, 3-5) fewer CRC deaths per 100 000 person-years, corresponding to percentage point reductions of 6.9 (95% CI, 6.0-7.9) for CRC incidence and 7.6 (95% CI, 5.7-9.6) for CRC mortality. The number needed to switch from sigmoidoscopy to colonoscopy screening was 560 (95% CI, 486-661) to prevent 1 CRC case and 1611 (95% CI, 1275-2188) to prevent 1 CRC death.Conclusions and relevanceThe findings of this comparative effectiveness study assessing long-term follow-up after CRC screening suggest that there was an additional preventive effect on CRC incidence and mortality associated with colonoscopy screening compared with sigmoidoscopy screening, but the additional preventive effect was less than what was achieved by introducing sigmoidoscopy screening where no screening existed. The results probably represent the upper limit of what may be achieved with colonoscopy screening compared with sigmoidoscopy screening.
| S-EPMC10905314 | biostudies-literature
Project description:BackgroundFlexible sigmoidoscopy and colonoscopy are both recommended colorectal cancer screening options, but their relative effectiveness needs clarification. The aim of this study was to compare the effectiveness of colonoscopy and flexible sigmoidoscopy for reduction of colorectal cancer incidence.MethodsWe conducted a case-control study within the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Cases were subjects age 70-85 years in the SEER-Medicare database diagnosed with CRC during 2004-2013. Up to 3 controls were matched to each case by birth year, sex, race, and SEER region. Receipt of screening colonoscopy or flexible sigmoidoscopy was ascertained from Medicare claims. Conditional logistic regression models were developed to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for a history of screening in cases vs. controls. We conducted secondary analyses by sex, race, endoscopist characteristics, and with varying timing and duration of the look-back period.ResultsReceipt of screening colonoscopy and sigmoidoscopy was associated with a 59% (OR 0.41, 95%CI 0.39, 0.43) and 22% reduction (OR 0.78, 95%CI 0.67, 0.92) in colorectal cancer incidence, respectively. Colonoscopy was associated with greater reduction in the distal colorectal cancer incidence (OR 0.22, 95%CI 0.20, 0.24) than proximal colorectal cancer incidence (OR 0.62, 95%CI 0.59, 0.66). Sigmoidoscopy was associated with a 52% reduction in distal colorectal cancer incidence (OR 0.48, 95%CI 0.37, 0.63), but with no reduction in proximal colorectal cancer incidence. These associations were stronger in men than in women. No differences by race or endoscopist characteristics were observed.ConclusionBoth screening colonoscopy and sigmoidoscopy were associated with reductions in overall colorectal cancer incidence, with a greater magnitude of reduction observed with colonoscopy.
| S-EPMC6894764 | biostudies-literature
Project description:IntroductionWhether and to what extent the relationship between physical activity (PA) and colorectal cancer (CRC) differs according to CRC-related genetic risk remains to be determined, and no studies to date have quantified how much genetically determined risk could be compensated for with active exercise.MethodsGenetic risk was quantified by a polygenic risk score (PRS) summarizing the estimated effect of 140 CRC-associated genetic variants. Associations of PA with CRC risk were estimated by multivariable logistic regression across PRS levels. We also compared the impact of PA and specific PA types to the PRS using "genetic risk equivalent (GRE)", a novel approach to enhance effective risk communication.ResultsAmong 5058 CRC patients and 4134 controls, we observed no significant association between overall PA level in quartiles and CRC risk. However, the highest versus lowest lifetime leisure time physical activity (LTPA) was associated with a 13% lower CRC risk [odds ratio 0.87, 95% confidence interval (CI) 0.77-1.00] independent of PRS levels (adjusted p value for interaction = 0.18). This effect was equivalent to the effect of having 11 percentiles lower PRS (GRE -10.6, 95% CI -20.7 to -0.6). The GRE (95% CI) for the highest lifetime sports tertile was -23.0 (-33.9 to -12.0).ConclusionsLTPA was inversely associated with CRC risk irrespective of polygenic risk for CRC, which reinforces the importance of LTPA in CRC prevention among the general population. Adequate sports activity can compensate for a large share of polygenic risk for CRC.
| S-EPMC9972112 | biostudies-literature
Project description:Background: Estimation of absolute risk of developing colorectal neoplasm is essential for personalized colorectal cancer (CRC) screening. We developed models to determine relative and absolute risks of colorectal neoplasm based on lifestyle and genetic variants and to validate their application in risk-adapted screening. Methods: We prospectively collected data from 203 advanced neoplasms, 464 non-advanced adenomas, and 1,213 healthy controls from a CRC screening trial in China in 2018-2019. The risk prediction model based on four lifestyle factors and a polygenic risk score (PRS) consisted of 19 CRC-associated single-nucleotide polymorphisms. We assessed the relative and 10-year absolute risks of developing colorectal neoplasm and the yield of a risk-adapted screening approach incorporating risk models, fecal immunochemical test, and colonoscopy. Results: Compared to the participants with favorable lifestyle and lower PRS, those with unfavorable lifestyle and higher PRS had 2.87- and 3.79-fold higher risk of colorectal neoplasm in males and females, respectively. For a 50-year-old man or a 50-year-old woman with the highest risk profile, the estimated 10-year absolute risk of developing colorectal neoplasm was 6.59% (95% CI: 6.53-6.65%) and 4.19% (95% CI: 4.11-4.28%), respectively, compared to 2.80% (95% CI: 2.78-2.81%) for men and 2.24% (95% CI: 2.21-2.27%) for women with the lowest risk profile. The positive predictive value for advanced neoplasm was 31.7%, and the number of colonoscopies needed to detect one advanced neoplasm was 3.2. Conclusion: The risk models, absolute risk estimates, and risk-adapted screening presented in our study would contribute to developing effective personalized CRC prevention and screening strategies.
| S-EPMC8324207 | biostudies-literature
Project description:IntroductionColonoscopy is considered the gold standard for colorectal cancer screening. Panoramic colonoscopy offers better visualization to decrease the adenoma miss rate.AimTo assess the influence of 330° panoramic view colonoscopy on adenoma and polyp detection rate, cecal intubation time, and examiner's comfort.Material and methodsThe study enrolled 421 patients aged 18-80 years who were eligible for colonoscopy screening. Patients with prior abdominal surgery, inflammatory bowel disease or after colorectal resections were excluded from the study. Patients were randomized to either standard frontal view (SFV) (Olympus Evis Exera III 190 CF-HQ190L) or the panoramic view colonoscopy (PVC) (FUSE CDVL slim c38). The study was approved by the local bioethics committee and registered at ClinicalTrial.gov (NCT02929381).ResultsThere were 214 patients examined with SFV and 207 with PVC. The mean age of patients was 64 ±12.26 years. The two groups were comparable. The median cecal intubation time was 234 s with SFV vs. 311 s with PVC (p < 0.001). There were no significant differences in CIR or withdrawal time. PVC made it possible to discover more diverticula in the ascending colon (p = 0.009). PDR with SFV was 34.6% and 40.1% with PVC (p = 0.242). A higher number of polyps was found in the transverse colon in the PVC group (p = 0.006). ADR and advanced ADR (aADR) in both groups were similar (26.4% vs. 27.1% and 14, 2% vs. 13.9%).ConclusionsColonoscopy with wide-angle endoscopes lasts longer and allows for the detection of more polyps and diverticula without affecting ADR and aADR. Our study did not reveal the superiority of wide-angle colonoscopy in colorectal cancer screening.
| S-EPMC8193743 | biostudies-literature