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Determining Risk of Colorectal Cancer and Starting Age of Screening Based on Lifestyle, Environmental, and Genetic Factors.

ABSTRACT: 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.

SUBMITTER: Jeon J

PROVIDER: S-EPMC5985207 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Determining Risk of Colorectal Cancer and Starting Age of Screening Based on Lifestyle, Environmental, and Genetic Factors.

Jeon Jihyoun J Du Mengmeng M Schoen Robert E RE Hoffmeister Michael M Newcomb Polly A PA Berndt Sonja I SI Caan Bette B Campbell Peter T PT Chan Andrew T AT Chang-Claude Jenny J Giles Graham G GG Gong Jian J Harrison Tabitha A TA Huyghe Jeroen R JR Jacobs Eric J EJ Li Li L Lin Yi Y Le Marchand Loïc L Potter John D JD Qu Conghui C Bien Stephanie A SA Zubair Niha N Macinnis Robert J RJ Buchanan Daniel D DD Hopper John L JL Cao Yin Y Nishihara Reiko R Rennert Gad G Slattery Martha L ML Thomas Duncan C DC Woods Michael O MO Prentice Ross L RL Gruber Stephen B SB Zheng Yingye Y Brenner Hermann H Hayes Richard B RB White Emily E Peters Ulrike U Hsu Li L

Gastroenterology 20180217 8

<h4>Background & aims</h4>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.<h4>Methods</h4>We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Color ...[more]

PMID: 29458155

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Project description:ImportanceBreast cancer screening guidelines acknowledge the need for earlier screening for women at increased risk but provide limited guidance for women with a family history of breast cancer. A risk-adapted starting age of screening for relatives of patients with breast cancer may help supplement current screening guidelines.ObjectiveTo identify the risk-adapted starting age of breast cancer screening on the basis of a woman's detailed family history.Design, setting, and participantsThis nationwide cohort study analyzed data recorded in the Swedish family-cancer data sets. All women born from 1932 onward and with at least 1 known first-degree relative (FDR) were included (N = 5 099 172). Data from January 1, 1958, to December 31, 2015, were collected. Data were analyzed from October 1, 2017, to March 31, 2019.ExposuresFamily history of breast cancer in FDRs and second-degree relatives (SDRs).Main outcomes and measuresPrimary invasive breast cancer diagnosis and the age at which women with different constellations of family history attained the risk level at which breast screening is usually recommended.ResultsOf the 5 099 172 women included in the study, 118 953 (2.3%) received a diagnosis of primary invasive breast cancer. A total of 102 751 women (86.4%; mean [SD] age at diagnosis, 55.9 [11.1] years) did not have family history of breast cancer in FDRs and SDRs at the time of their diagnosis. Risk-adapted starting age of breast cancer screening varied by number of FDRs and SDRs with breast cancer diagnosis and the age at diagnosis of the FDRs. For example, for screening recommendation at age 50 years for the general population (2.2% 10-year cumulative risk), women with multiple affected FDRs, with the youngest affected relative receiving a diagnosis before age 50 years, reached the benchmark risk level at age 27 years. When the youngest relative received a diagnosis after age 50 years, however, this risk level was attained at age 36 years.Conclusions and relevanceThis study identifies possible risk-based starting ages for breast cancer screening based on population-based registers. These results may serve as high-quality evidence to supplement current screening guidelines for relatives of patients with breast cancer.

Project description:New methods are needed to improve health behaviors, such as adherence to colorectal cancer (CRC) screening. Personalized genetic information to guide medical decisions is increasingly available. Whether such information motivates behavioral change is unknown.To determine whether individualized genetic and environmental risk assessment (GERA) of CRC susceptibility improves adherence to screening in average-risk persons.2-group, randomized, controlled trial. (ClinicalTrials.gov: NCT0087360).4 medical school-affiliated primary care practices.783 participants at average risk for CRC who were not adherent to screening at study entry.Participants were randomly assigned to usual care or GERA, which evaluated methylenetetrahydrofolate reductase polymorphisms and serum folate levels. On the basis of prespecified combinations of polymorphisms and serum folate levels, GERA recipients were told that they were at elevated or average risk for CRC.The primary outcome was CRC screening within 6 months of study entry.Overall screening rates for CRC did not statistically significant differ between the usual care (35.7%) and GERA (33.1%) groups. After adjustment for baseline participant factors, the odds ratio for screening completion for GERA versus usual care was 0.88 (95% CI, 0.64 to 1.22). Within the GERA group, screening rates did not significantly differ between average-risk (38.1%) and elevated-risk (26.9%) participants. Odds ratios for elevated- versus average-risk participants remained nonsignificant after adjustment for covariates (odds ratio, 0.75 [CI, 0.39 to 1.42]).Only 1 personalized genetic and environmental interaction and 1 health behavior (CRC screening) were assessed.In average-risk persons, CRC screening uptake was not positively associated with feedback from a single personalized GERA. Additional studies will be required to evaluate whether other approaches to providing GERA affect screening utilization differently. These findings raise concern about the effectiveness of moderately predictive assessment of genetic risk to promote favorable health care behavior.National Institutes of Health.

Dataset Information

Determining Risk of Colorectal Cancer and Starting Age of Screening Based on Lifestyle, Environmental, and Genetic Factors.

Publications

Determining Risk of Colorectal Cancer and Starting Age of Screening Based on Lifestyle, Environmental, and Genetic Factors.

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