Dataset Information

Genetic Risk Score, Combined Lifestyle Factors and Risk of Colorectal Cancer.

ABSTRACT:

Purpose

Both genetic and lifestyle factors contribute to the risk of colorectal cancer, but each individual factor has a limited effect. Therefore, we investigated the association between colorectal cancer and the combined effects of genetic factors or/and lifestyle risk factors.

Materials and methods

In a case-control study of 632 colorectal cancer patients and 1,295 healthy controls, we quantified the genetic risk score for colorectal cancer using 13 polymorphisms. Furthermore, we determined a combined lifestyle risk score including obesity, physical activity, smoking, alcohol consumption, and dietary inflammatory index. The associations between colorectal cancer and risk score using these factors were examined using a logistic regression model.

Results

Higher genetic risk scores were associated with an increased risk of colorectal cancer (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.89 to 3.49 for the highest tertile vs. lowest tertile). Among the modifiable factors, previous body mass index, physical inactivity, heavy alcohol consumption, and a high inflammatory diet were associated with an increased risk of colorectal cancer. A higher lifestyle risk score was associated with an increased risk of colorectal cancer (OR, 5.82; 95% CI, 4.02 to 8.44 for the highest tertile vs. lowest tertile). This association was similar in each genetic risk category.

Conclusion

Adherence to a healthy lifestyle is associated with a substantially reduced risk of colorectal cancer regardless of individuals' genetic risk.

SUBMITTER: Cho YA

PROVIDER: S-EPMC6639208 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Genetic Risk Score, Combined Lifestyle Factors and Risk of Colorectal Cancer.

Cho Young Ae YA Lee Jeonghee J Oh Jae Hwan JH Chang Hee Jin HJ Sohn Dae Kyung DK Shin Aesun A Kim Jeongseon J

Cancer research and treatment 20181018 3

<h4>Purpose</h4>Both genetic and lifestyle factors contribute to the risk of colorectal cancer, but each individual factor has a limited effect. Therefore, we investigated the association between colorectal cancer and the combined effects of genetic factors or/and lifestyle risk factors.<h4>Materials and methods</h4>In a case-control study of 632 colorectal cancer patients and 1,295 healthy controls, we quantified the genetic risk score for colorectal cancer using 13 polymorphisms. Furthermore, ...[more]

PMID: 30336659

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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.

Project description:BackgroundNutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population.MethodsThe model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70?years who were free of cancer at study baseline (1992-2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15?years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed.ResultsThe final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell's C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement?=?0.307 (95% CI 0.264-0.352)), and especially for young individuals below 45?years (continuous net reclassification improvement?=?0.364 (95% CI 0.084-0.575)).ConclusionsLiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.

Dataset Information

Genetic Risk Score, Combined Lifestyle Factors and Risk of Colorectal Cancer.

Purpose

Materials and methods

Results

Conclusion

Publications

Genetic Risk Score, Combined Lifestyle Factors and Risk of Colorectal Cancer.

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