Polygenic risk scores for the prediction of common cancers in East Asians: A population-based prospective cohort study

  1. Peh Joo Ho
  2. Iain BeeHuat Tan
  3. Dawn Qingqing Chong
  4. Chiea Chuen Khor
  5. Jian-Min Yuan
  6. Woon-Puay Koh
  7. Rajkumar Dorajoo  Is a corresponding author
  8. Jingmei Li  Is a corresponding author
  1. Genome Institute of Singapore, Singapore
  2. National Cancer Centre Singapore, Singapore
  3. UPMC Hillman Cancer Center, United States
  4. National University of Singapore, Singapore

Abstract

Background: To evaluate the utility of polygenic risk scores (PRS) in identifying high-risk individuals, different publicly available PRS for breast (n=85), prostate (n=37), colorectal (n=22) and lung cancers (n=11) were examined in a prospective study of 21,694 Chinese adults.

Methods: We constructed PRS using weights curated in the online PGS Catalog. PRS performance was evaluated by distribution, discrimination, predictive ability, and calibration. Hazard ratios (HR) and corresponding confidence intervals [CI] of the common cancers after 20 years of follow-up were estimated using Cox proportional hazard models for different levels of PRS.

Results: A total of 495 breast, 308 prostate, 332 female-colorectal, 409 male-colorectal, 181 female-lung and 381 male-lung incident cancers were identified. The area under receiver operating characteristic curve for the best performing site-specific PRS were 0.61 (PGS000873, breast), 0.70 (PGS00662, prostate), 0.65 (PGS000055, female-colorectal), 0.60 (PGS000734, male-colorectal) and 0.56 (PGS000721, female-lung), and 0.58 (PGS000070, male-lung), respectively. Compared to the middle quintile, individuals in the highest cancer-specific PRS quintile were 64% more likely to develop cancers of the breast, prostate, and colorectal. For lung cancer, the lowest cancer-specific PRS quintile was associated with 28-34% decreased risk compared to the middle quintile. In contrast, the hazard ratios observed for quintiles 4 (female-lung: 0.95 [0.61-1.47]; male-lung: 1.14 [0.82-1.57]) and 5 (female-lung: 0.95 [0.61-1.47]) were not significantly different from that for the middle quintile.

Conclusions: Site-specific PRSs can stratify the risk of developing breast, prostate, and colorectal cancers in this East Asian population. Appropriate correction factors may be required to improve calibration.

Funding This work is supported by the National Research Foundation Singapore (NRF-NRFF2017-02), PRECISION Health Research, Singapore (PRECISE) and the Agency for Science, Technology and Research (A*STAR). WP Koh was supported by National Medical Research Council, Singapore (NMRC/CSA/0055/2013). CC Khor was supported by National Research Foundation Singapore (NRF-NRFI2018-01). Rajkumar Dorajoo received a grant from the Agency for Science, Technology and Research Career Development Award (A*STAR CDA - 202D8090), and from Ministry of Health Healthy Longevity Catalyst Award (HLCA20Jan-0022). The Singapore Chinese Health Study was supported by grants from the National Medical Research Council, Singapore (NMRC/CIRG/1456/2016) and the U.S. National Institutes of Health [NIH] (R01 CA144034 and UM1 CA182876).

Data availability

All polygenic risk scores used in this study are publicly available in the PGS Catalog (https://www.pgscatalog.org).The data that support the findings of our study are available from the corresponding authors of the study upon reasonable request (Dr Rajkumar s/o Dorajoo, dorajoor@gis.a-star.edu.sg and Dr Jingmei Li, lijm1@gis.a-star.edu.sg). More information regarding the data access to SCHS can be found at: https://sph.nus.edu.sg/research/cohort-schs/. The data are not publicly available due to Singapore laws.Source Data 1 contain the numerical data used to generate the figure 1.The code for the study is uploaded as Source Code 1.

The following previously published data sets were used

Article and author information

Author details

  1. Peh Joo Ho

    Genome Institute of Singapore, Singapore, Singapore
    Competing interests
    No competing interests declared.
  2. Iain BeeHuat Tan

    Genome Institute of Singapore, Singapore, Singapore
    Competing interests
    No competing interests declared.
  3. Dawn Qingqing Chong

    Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
    Competing interests
    No competing interests declared.
  4. Chiea Chuen Khor

    Genome Institute of Singapore, Singapore, Singapore
    Competing interests
    No competing interests declared.
  5. Jian-Min Yuan

    UPMC Hillman Cancer Center, Pittsburgh, United States
    Competing interests
    No competing interests declared.
  6. Woon-Puay Koh

    Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Competing interests
    No competing interests declared.
  7. Rajkumar Dorajoo

    Genome Institute of Singapore, Singapore, Singapore
    For correspondence
    dorajoor@gis.a-star.edu.sg
    Competing interests
    Rajkumar Dorajoo, received a grant from the Agency for Science, Technology and Research Career Development Award (A*STAR CDA - 202D8090, and from Ministry of Health Healthy Longevity Catalyst Award (HLCA20Jan-0022). The author has no other competing interests to declare..
  8. Jingmei Li

    Genome Institute of Singapore, Singapore, Singapore
    For correspondence
    lijm1@gis.a-star.edu.sg
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8587-7511

Funding

National Research Foundation Singapore (PRECISE)

  • Jingmei Li

National Medical Research Council (NMRC/CSA/0055/2013)

  • Woon-Puay Koh

National Research Foundation Singapore (NRF-NRFI2018-01)

  • Chiea Chuen Khor

Ministry of Health -Singapore (HLCA20Jan-0022)

  • Rajkumar Dorajoo

National Institutes of Health (R01 CA144034 and UM1 CA182876)

  • Jian-Min Yuan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study was approved by the Institutional Review Boards of the National University of Singapore, University of Pittsburgh, and the Agency for Science, Technology and Research (A*STAR, reference number 2022-042). Written, informed consent was obtained from all study participants.

Copyright

© 2023, Ho et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Peh Joo Ho
  2. Iain BeeHuat Tan
  3. Dawn Qingqing Chong
  4. Chiea Chuen Khor
  5. Jian-Min Yuan
  6. Woon-Puay Koh
  7. Rajkumar Dorajoo
  8. Jingmei Li
(2023)
Polygenic risk scores for the prediction of common cancers in East Asians: A population-based prospective cohort study
eLife 12:e82608.
https://doi.org/10.7554/eLife.82608

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https://doi.org/10.7554/eLife.82608

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