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Comparative Study
. 2018 Jun;154(8):2152-2164.e19.
doi: 10.1053/j.gastro.2018.02.021. Epub 2018 Feb 17.

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

Jihyoun Jeon  1 , Mengmeng Du  2 , Robert E Schoen  3 , Michael Hoffmeister  4 , Polly A Newcomb  5 , Sonja I Berndt  6 , Bette Caan  7 , Peter T Campbell  8 , Andrew T Chan  9 , Jenny Chang-Claude  4 , Graham G Giles  10 , Jian Gong  5 , Tabitha A Harrison  5 , Jeroen R Huyghe  5 , Eric J Jacobs  8 , Li Li  11 , Yi Lin  5 , Loïc Le Marchand  12 , John D Potter  5 , Conghui Qu  5 , Stephanie A Bien  5 , Niha Zubair  5 , Robert J Macinnis  10 , Daniel D Buchanan  13 , John L Hopper  14 , Yin Cao  15 , Reiko Nishihara  16 , Gad Rennert  17 , Martha L Slattery  18 , Duncan C Thomas  19 , Michael O Woods  20 , Ross L Prentice  5 , Stephen B Gruber  21 , Yingye Zheng  5 , Hermann Brenner  4 , Richard B Hayes  22 , Emily White  5 , Ulrike Peters  23 , Li Hsu  24 ; Colorectal Transdisciplinary Study and Genetics and Epidemiology of Colorectal Cancer Consortium
Affiliations
Comparative Study

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

Jihyoun Jeon et al. Gastroenterology. 2018 Jun.

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.

Keywords: CORECT; Colon Cancer; Colonoscopy; GECCO.

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Conflict of interest statement

Disclosures: There are no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Estimate of 10-year absolute risk of CRC at 1st, 5th, 10th, 50th, 90th, 95th, 99th percentiles of risk score under various models for an individual aged 50 years who did not have a prior endoscopy. FH: family history only model, FH+E: family history and environmental risk score (E-score) model, FH+G: family history and genetic risk score (G-score) model, FH+E+G: family history and E-score and G-score model.
Figure 2
Figure 2
Recommended age to start CRC screening by various risk scores, which was based on both environmental risk score (E-score) and genetic risk score (G-score). The horizontal lines represent the recommended age for the first endoscopy depending on family history in the current screening guideline for CRC. The risk threshold to determine the age for the first screening was set as the average of 10-year CRC risks for a 50-year-old man (1.25%) and woman (0.68%), i.e., (1.25%+0.68%)/2=0.97%, who have not previously received an endoscopy.
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Comment in

  • Personalized screening for colorectal cancer.
    Kuipers EJ, Spaander MC. Kuipers EJ, et al. Nat Rev Gastroenterol Hepatol. 2018 Jul;15(7):391-392. doi: 10.1038/s41575-018-0015-8. Nat Rev Gastroenterol Hepatol. 2018. PMID: 29713023 No abstract available.

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