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Effects of genetic and environmental factors on colorectal cancer among Koreans : use of genetic risk score, gene-gene and gene-environment interaction (Korean Cancer Prevention Study-II, KCPS-II)

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 유전위험점수, 유전-유전 및 유전-환경 상호작용 이용 (한국인 암 예방연구 II : KCPS-II) 
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Dept. of Public Health/박사
Background Colorectal cancer (CRC) is among the leading causes of cancer deaths and can be caused by environmental factors as well as genetic factors. Therefore, this study was conducted to predict a CRC risk using an environmental risk score (ERS) as well as a genetic risk score (GRS) and gene-gene interaction and evaluate the effects of ERS, GRS, gene-gene interaction and gene-environment risk scores (GERS) on the risk for CRC among Koreans.Methods and Materials The Korean Cancer Prevention Study-II (KCPS-II) included 266,258 individuals, 20-77 years of age, who visited 16 health promotion centers nationwide from April 2004 to December 2008. This study included 325 confirmed CRC cases (men, 237; women, 88) and 977 randomly selected controls (men, 554; women, 422). Environmental risk score (ERS) included factors such as: age, smoking status, alcohol consumption and body mass index (BMI). For genetic factors, a genome-wide association study (GWAS) was performed using the Affymetrix Genome-wide Human SNP array 5.0. GRS were calculated with most significantly associated single-nucleotide polymorphisms (SNPs) through GWAS. Gene-gene interactions were evaluated using multifactor dimensionality reduction (MDR) analysis. Results For both men and women, inclusion of counted GRS or weighted GRS and further inclusion of gene-gene interaction by MDR analysis increased the area under the curve (AUC) by 6.2-10.8% and 0.1-0.5% beyond the AUC provided by environmental factors and the AUC provided by environmental factors plus counted GRS or weighted GRS, respectively. In combination of ERS and GRS (GERS) to determine the risk for CRC, men and women with ERS 1-4 points and GRS in the highest quartile had significantly increased risk for CRC compared to those with ERS 1-4 points and GRS in the lowest quartile of GRS. Moreover, in the highest quartile of GRS, the risk for CRC increased even more in men and women with ERS 8-10 points compared to those with ERS 1-4 points. Conclusion Our findings suggest that GRS as well as gene-gene interaction improved the prediction of CRC risk when considered in conjunction with environmental factors such as age, family history of CRC, BMI, physical activity and fasting blood glucose. Findings in this current study might provide a small piece of evidence in prediction of CRC risk for reducing its prevalence and incidence rates. The prediction of CRC risk in this study also needs to be validated or replicated in an independent population. Therefore, further studies are needed to be applied to the general population.
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1. College of Medicine (의과대학) > Others (기타) > 5. Others
Yonsei Authors
Jo, Jae Seong(조재승)
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