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Evaluating the predictive value of genetic risk score in colorectal cancer among Chinese Han population

Journal of Human Genetics volume 65, pages 271–279 (2020)Cite this article

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Abstract

Increasing single nucleotide polymorphisms (SNPs) have been identified to be associated with colorectal cancer (CRC). We aimed to investigate whether genetic risk scores (GRS) that aggregate information from multiple genetic variants can predict the risk of CRC in a Chinese population. Fifty candidate SNPs were selected to explore the associations with CRC in a discovery sample with 1002 CRC cases and 999 healthy controls. We modeled the significant SNPs identified by the case–control study as a multilocus weighted GRS and estimated the association of GRS with CRC. Furthermore, 300 pairs of cases and controls were included as a validation sample to confirm the finding. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive power of GRS in CRC. A total of seven SNPs were found to increase the risk of CRC, and two SNPs were found to be negatively associated with CRC in the discovery sample. Relative to participants with the lowest quartile of GRS, those with the highest quartile had a 2.64-fold (95% CI: 1.99–3.51) higher risk for CRC. For every 0.1 point of GRS increase, the risk of CRC increase by 11% (95% CI: 8–14%). AUROC for GRS alone were 0.59 (95% CI: 0.57–0.62) and 0.52 (95% CI: 0.46–0.58) in the discovery and validation sample, respectively. AUROC increased to 0.62 (95% CI: 0.59–0.64) and 0.71 (95% CI: 0.65–0.76) by combining environmental risk factors. Our findings support an association between GRS and risk of CRC, which provides evidence of improved prediction model for CRC in China.

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Acknowledgements

This work was supported by the National Key Basic Research Program (973 program No. 2015CB554003), and the National Natural Science Foundation of China (No. 81673262 and 81602917). We would like to thank all the patients and control subjects for their participation in this study. We gratefully acknowledge Department of Gastrointestinal Surgery of the Shaoxing People’s Hospital for their valuable help.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou, China

    Ding Ye, Danjie Jiang, Simeng Gu, Yingying Mao, Sangni Qian, Shujuan Lin, Kunhong Zhong, Mingjuan Jin & Kun Chen

  2. School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China

    Ding Ye & Yingying Mao

  3. Jiashan Institute of Cancer Prevention and Treatment, Jiaxing, China

    Qilong Li & Jinhua Yang

  4. Cancer Institute, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Kun Chen

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Ye, D., Jiang, D., Gu, S. et al. Evaluating the predictive value of genetic risk score in colorectal cancer among Chinese Han population. J Hum Genet 65, 271–279 (2020). https://doi.org/10.1038/s10038-019-0703-4

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