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Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment

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Listed:
  • Junyi Xin

    (Nanjing Medical University
    Nanjing Medical University
    Nanjing Medical University)

  • Dongying Gu

    (Nanjing Medical University)

  • Shuwei Li

    (Nanjing Medical University
    Nanjing Medical University)

  • Sangni Qian

    (Zhejiang University School of Medicine
    The Second Affiliated Hospital, Zhejiang University School of Medicine)

  • Yifei Cheng

    (Nanjing Medical University
    Nanjing Medical University)

  • Wei Shao

    (Nanjing Medical University
    Nanjing Medical University)

  • Shuai Ben

    (Nanjing Medical University
    Nanjing Medical University)

  • Silu Chen

    (Nanjing Medical University
    Nanjing Medical University)

  • Linjun Zhu

    (The First Affiliated Hospital of Nanjing Medical University)

  • Mingjuan Jin

    (Zhejiang University School of Medicine
    The Second Affiliated Hospital, Zhejiang University School of Medicine)

  • Kun Chen

    (Zhejiang University School of Medicine
    The Second Affiliated Hospital, Zhejiang University School of Medicine)

  • Zhibin Hu

    (Nanjing Medical University)

  • Zhengdong Zhang

    (Nanjing Medical University
    Nanjing Medical University)

  • Mulong Du

    (Nanjing Medical University)

  • Hongbing Shen

    (Nanjing Medical University)

  • Meilin Wang

    (Nanjing Medical University
    Nanjing Medical University
    Nanjing Medical University)

Abstract

The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD = 1.99, P = 1.76 × 10−8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P = 3.21 × 10−14; 543 patients) and 1.80 (P = 1.11 × 10−9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. Therefore, our findings demonstrate the integrated contribution of pathologic characteristics, germline variants, and lifestyle exposure to the prognosis of colorectal cancer patients.

Suggested Citation

  • Junyi Xin & Dongying Gu & Shuwei Li & Sangni Qian & Yifei Cheng & Wei Shao & Shuai Ben & Silu Chen & Linjun Zhu & Mingjuan Jin & Kun Chen & Zhibin Hu & Zhengdong Zhang & Mulong Du & Hongbing Shen & Me, 2024. "Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47204-9
    DOI: 10.1038/s41467-024-47204-9
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    References listed on IDEAS

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    1. Gerhard Tutz & Harald Binder, 2006. "Generalized Additive Modeling with Implicit Variable Selection by Likelihood-Based Boosting," Biometrics, The International Biometric Society, vol. 62(4), pages 961-971, December.
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