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Comparison of the efficiency of colorectal cancer screening programs based on age and genetic risk for reduction of colorectal cancer mortality.

ABSTRACT: Given that colorectal cancer risk depends partly on inherited factors, screening program efficiency may be increased by incorporating genetic factors. We compared the efficiency of screening based on age and genetic risk in a simulated population. We simulated a population matching the size, age distribution and colorectal cancer incidence and mortality of Australia. We also simulated the distribution of genetic risk for colorectal cancer based on the expected number of inherited risk alleles of 45 single-nucleotide polymorphisms (SNPs) previously reported as associated with colorectal cancer. We compared the expected colorectal cancer deaths under three screening programs; age-based, genetic-based and combined age-based and genetic-based. The age-based program would prevent 25.4 deaths per 100?000 invited to screen, none of which would be under age 50; the genetic program would prevent 26.2 deaths per 100?000 invited to screen, 16 of which would be under age 50; and the combined program would prevent 24.4 deaths per 100?000 invited to screen, 16 of which would be under age 50. Genetic testing of 1.5 million 45-49 year olds would identify 91% of the people aged under 50 at sufficient risk to warrant screening, potentially saving 16 colorectal cancer deaths each year. Screening eligibility based on genetic risk profile for age is as efficient as eligibility based on age alone for preventing colorectal cancer mortality, but identifies an additional 7% of the population at sufficient risk to benefit from screening who would not normally be screened given they are aged under 50 years.

SUBMITTER: Stanesby O

PROVIDER: S-EPMC5520072 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Comparison of the efficiency of colorectal cancer screening programs based on age and genetic risk for reduction of colorectal cancer mortality.

Stanesby Oliver O Jenkins Mark M

European journal of human genetics : EJHG 20170510 7

Given that colorectal cancer risk depends partly on inherited factors, screening program efficiency may be increased by incorporating genetic factors. We compared the efficiency of screening based on age and genetic risk in a simulated population. We simulated a population matching the size, age distribution and colorectal cancer incidence and mortality of Australia. We also simulated the distribution of genetic risk for colorectal cancer based on the expected number of inherited risk alleles of ...[more]

PMID: 28488675

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Project description:BACKGROUND:The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality. METHODS:From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained. RESULTS:Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P<0.001). Significant reductions were observed in the incidence of both distal colorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; P<0.001) and proximal colorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P=0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; P<0.001). Mortality from distal colorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; P<0.001); mortality from proximal colorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P=0.81). CONCLUSIONS:Screening with flexible sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence (in both the distal and proximal colon) and mortality (distal colon only). (Funded by the National Cancer Institute; PLCO ClinicalTrials.gov number, NCT00002540.).

Project description:ImportanceColorectal cancer (CRC) is a leading cause of cancer-related mortality globally, with increasing incidence and mortality in Latin America. CRC screening programs can reduce disease burden, but information on screening programs in Latin America is limited.ObjectiveTo describe characteristics (eg, type of program, uptake, neoplastic yield) of CRC screening programs in Latin America.Data sourcesPubMed, Ovid MEDLINE, EMBASE, Cochrane, PsycINFO, Web of Science Core Collection, LILACS, and SciELO were searched from inception to February 2023. Relevant references from bibliographies, conference proceedings, and gray literature were considered. The search strategy included English, Spanish, and Portuguese terms.Study selectionIncluded were studies of CRC screening programs in Latin America using fecal immunochemical test (FIT) or colonoscopy as the primary screening method. Four reviewers independently assessed study eligibility based on titles, with review of abstracts and full texts as needed.Data extraction and synthesisGuidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed for data abstraction and quality assessment. Descriptive information was extracted, and data were pooled using a random-effects model.Main outcomes and measuresProgram performance indicators included rates of participation and FIT positivity, adenoma detection rate (ADR), advanced adenoma detection rate (AADR), CRC detection rate, and colonoscopy quality indicators.ResultsThere were 17 studies included from upper middle-income and high-income countries in Latin America with a total of 123 929 participants. Thirteen studies used FIT as the initial screening method, whereas 4 used screening colonoscopy. The participation rate in FIT-based programs was 85.8% (95% CI, 78.5%-91.4%). FIT positivity rates were 15.2% (95% CI, 9.6%-21.8%) for the 50-ng/mL threshold and 9.7% (95% CI, 6.8%-13.0%) for the 100-ng/mL threshold. For FIT-based studies, the pooled ADR was 39.0% (95% CI, 29.3%-49.2%) and CRC detection rate was 4.9% (95% CI, 2.6%-7.9%); for screening colonoscopy-based studies, the pooled ADR was 19.9% (95% CI, 15.5%-24.8%) and CRC detection rate was 0.4% (95% CI, 0.1%-0.8%).Conclusions and relevanceThis systematic review and meta-analysis suggests that CRC screening in upper middle-income countries in Latin America is feasible, detecting rates of neoplasia comparable with those of high-income regions. Population-based screening programs should be developed or enhanced in these settings. There is a knowledge gap regarding feasibility and yield of screening programs in lower middle-income countries.

Project description:BACKGROUND & AIMS:Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening. METHODS:We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve values, adjusting for study, age, and endoscopy history for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results program registry. RESULTS:In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an area under the receiver operating characteristic curve value of 0.63 (95% confidence interval, 0.62-0.64) for men and 0.62 (95% confidence interval, 0.61-0.63) for women; area under the receiver operating characteristic curve values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk. CONCLUSIONS:We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies.

Dataset Information

Comparison of the efficiency of colorectal cancer screening programs based on age and genetic risk for reduction of colorectal cancer mortality.

Publications

Comparison of the efficiency of colorectal cancer screening programs based on age and genetic risk for reduction of colorectal cancer mortality.

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