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Original research
Universal germline testing among patients with colorectal cancer: clinical actionability and optimised panel
  1. Wu Jiang1,
  2. Lin Li2,
  3. Chuan-Feng Ke3,
  4. Wei Wang4,
  5. Bin-Yi Xiao1,
  6. Ling-Heng Kong1,
  7. Jing-Hua Tang1,
  8. Yuan Li1,
  9. Xiao-Dan Wu1,
  10. Ying Hu2,
  11. Wei-Hua Guo2,
  12. Si-Zhen Wang2,
  13. De-Sen Wan1,
  14. Rui-Hua Xu5,
  15. Zhi-Zhong Pan1,
  16. Pei-Rong Ding1
  1. 1State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
  2. 2Genetron Health (Beijing) Technology, Co. Ltd, Beijing, China
  3. 3Department of General Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
  4. 4Department of Gastrointestinal Surgery, Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China
  5. 5Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
  1. Correspondence to Prof. Pei-Rong Ding, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; dingpr{at}; Prof. Zhi-Zhong Pan, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; panzhzh{at}


Purpose Universal germline testing in patients with colorectal cancer (CRC) with a multigene panel can detect various hereditary cancer syndromes. This study was performed to understand how to choose a testing panel and whether the result would affect clinical management.

Methods We prospectively enrolled 486 eligible patients with CRC, including all patients with CRC diagnosed under age 70 years and patients with CRC diagnosed over 70 years with hereditary risk features between November 2017 and January 2018. All participants received germline testing for various hereditary cancer syndromes.

Results The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes was 7.8% (38/486), including 25 PVs in genes with high-risk CRC susceptibility (the minimal testing set) and 13 PVs in genes with moderate-risk CRC susceptibility or increased cancer risk other than CRC (the additional testing set). All the clinically relevant PVs were found in patients diagnosed under age 70 years. Among them, 11 patients would not have been diagnosed if testing reserved to present guidelines. Most (36/38) of the patients with PVs benefited from enhanced surveillance and tailored treatment. PVs in genes from the minimal testing set were found in all age groups, while patients carried PVs in genes from the additional testing set were older than 40 years.

Conclusion Universal germline testing for cancer susceptibility genes should be recommended among all patients with CRC diagnosed under age 70 years. A broad panel including genes from the additional testing set might be considered for patients with CRC older than 40 years to clarify inheritance risks.

Trial registration number NCT03365986.

  • congenital
  • hereditary
  • and neonatal diseases and abnormalities
  • gastroenterology
  • genetic carrier screening
  • genetic counseling

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  • WJ, LL, C-FK and WW contributed equally.

  • Contributors WJ, LL, and PRD conducted the conceptualisation and drafted the manuscript. WJ, WW and CFK collected the data. LL and BYX analysed the data. PRD and ZZP supervised the project. All authors approved the final version.

  • Funding This work was supported by the National Key R&D Program of China (Grant No. 2017YFC0908200), the National Natural Science Foundation of China (Grant No. 81871971), the Science and Technology Planning Project of Guangzhou (Grant No. 201803010117), the Medical Scientific Research Foundation of Guangdong Province (Grant No. A2020392) and the Fundamental Research Funds for young teachers of Sun Yat-sen University (Grant No. 20ykpy165).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the clinical research ethics committee of Sun Yat-sen University Cancer Center and all patients provided written informed consent to participate in the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All data have been recorded at Sun Yat-sen University Cancer Center for future reference (, RDDA2019001141).

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.