domingo, 25 de febrero de 2018

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

2018 Feb 16. pii: S0016-5085(18)30224-5. doi: 10.1053/j.gastro.2018.02.021. [Epub ahead of print]

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

Jeon J1, Du M2, Schoen RE3, Hoffmeister M4, Newcomb PA5, Berndt SI6, Caan B7, Campbell PT8, Chan AT9, Chang-Claude J4, Giles GG10, Gong J5, Harrison TA5, Huyghe JR5, Jacobs EJ8, Li L11, Lin Y5, Le Marchand L12, Potter JD5, Qu F5, Bien SA5, Zubair N5, Macinnis RJ10, Buchanan DD13, Hopper JL14, Cao Y15, Nishihara R16, Rennert G17, Slattery ML18, Thomas DC19, Woods MO20, Prentice RL5, Gruber SB21, Zheng Y5, Brenner H4, Hayes RB22, White E5, Peters U23, Hsu L24; Colorectal Transdisciplinary (CORECT) Study and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO).

Author information

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 (AUC) values, adjusting for study, age, and endoscopy findings 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 AUC value of 0.63 (95% CI, 0.62-0.64) for men and 0.62 (95% CI, 0.61-0.63) for women; AUC 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.