Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank
Background: Polygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain. Methods and findings: We constructed 80 PRSs for the 13 most common cancers using seven schemes and evalua...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
Public Library of Science
2025
|
| _version_ | 1826317729642053632 |
|---|---|
| author | Zhu, M Zhu, X Han, Y Ma, Z Ji, C Wang, T Yan, C Song, C Yu, C Sun, D Jiang, Y Chen, J Yang, L Chen, Y Du, H Walters, R Millwood, IY Dai, J Ma, H Zhang, Z Chen, Z Hu, Z Lv, J Jin, G |
| author_facet | Zhu, M Zhu, X Han, Y Ma, Z Ji, C Wang, T Yan, C Song, C Yu, C Sun, D Jiang, Y Chen, J Yang, L Chen, Y Du, H Walters, R Millwood, IY Dai, J Ma, H Zhang, Z Chen, Z Hu, Z Lv, J Jin, G |
| author_sort | Zhu, M |
| collection | OXFORD |
| description | Background: Polygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain. Methods and findings: We constructed 80 PRSs for the 13 most common cancers using seven schemes and evaluated these PRSs in 100,219 participants from the China Kadoorie Biobank (CKB). The optimal PRSs with the highest discriminatory ability were used to define genetic risk, and their site-specific and cross-cancer associations were assessed. We modeled 10-year absolute risk trajectories for each cancer across risk strata defined by PRSs and modifiable risk scores and quantified the explained relative risk (ERR) of PRSs with modifiable risk factors for different cancers. More than 60% (50/80) of the PRSs demonstrated significant associations with the corresponding cancer outcomes. Optimal PRSs for nine common cancers were identified, with each standard deviation increase significantly associated with corresponding cancer risk (hazard ratios (HRs) ranging from 1.20 to 1.76). Compared with participants at low genetic risk and reduced modifiable risk scores, those with high genetic risk and elevated modifiable risk scores had the highest risk of incident cancer, with HRs ranging from 1.97 (95% confidence interval (CI): 1.11–3.48 for cervical cancer, P = 0.020) to 8.26 (95% CI: 1.92–35.46 for prostate cancer, P = 0.005). We observed nine significant cross-cancer associations for PRSs and found the integration of PRSs significantly increased the prediction accuracy for most cancers. The PRSs contributed 2.6%–20.3%, while modifiable risk factors explained 2.3%–16.7% of the ERR in the Chinese population. Conclusions: The integration of existing evidence has facilitated the development of PRSs associated with nine common cancer risks in the Chinese population, potentially improving clinical risk assessment. |
| first_indexed | 2025-03-11T16:58:32Z |
| format | Journal article |
| id | oxford-uuid:c638ea3b-a43b-4a17-9839-352e3f67d44b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-03-11T16:58:32Z |
| publishDate | 2025 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:c638ea3b-a43b-4a17-9839-352e3f67d44b2025-02-28T20:16:27ZPolygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie BiobankJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c638ea3b-a43b-4a17-9839-352e3f67d44bEnglishJisc Publications RouterPublic Library of Science2025Zhu, MZhu, XHan, YMa, ZJi, CWang, TYan, CSong, CYu, CSun, DJiang, YChen, JYang, LChen, YDu, HWalters, RMillwood, IYDai, JMa, HZhang, ZChen, ZHu, ZLv, JJin, GBackground: Polygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain. Methods and findings: We constructed 80 PRSs for the 13 most common cancers using seven schemes and evaluated these PRSs in 100,219 participants from the China Kadoorie Biobank (CKB). The optimal PRSs with the highest discriminatory ability were used to define genetic risk, and their site-specific and cross-cancer associations were assessed. We modeled 10-year absolute risk trajectories for each cancer across risk strata defined by PRSs and modifiable risk scores and quantified the explained relative risk (ERR) of PRSs with modifiable risk factors for different cancers. More than 60% (50/80) of the PRSs demonstrated significant associations with the corresponding cancer outcomes. Optimal PRSs for nine common cancers were identified, with each standard deviation increase significantly associated with corresponding cancer risk (hazard ratios (HRs) ranging from 1.20 to 1.76). Compared with participants at low genetic risk and reduced modifiable risk scores, those with high genetic risk and elevated modifiable risk scores had the highest risk of incident cancer, with HRs ranging from 1.97 (95% confidence interval (CI): 1.11–3.48 for cervical cancer, P = 0.020) to 8.26 (95% CI: 1.92–35.46 for prostate cancer, P = 0.005). We observed nine significant cross-cancer associations for PRSs and found the integration of PRSs significantly increased the prediction accuracy for most cancers. The PRSs contributed 2.6%–20.3%, while modifiable risk factors explained 2.3%–16.7% of the ERR in the Chinese population. Conclusions: The integration of existing evidence has facilitated the development of PRSs associated with nine common cancer risks in the Chinese population, potentially improving clinical risk assessment. |
| spellingShingle | Zhu, M Zhu, X Han, Y Ma, Z Ji, C Wang, T Yan, C Song, C Yu, C Sun, D Jiang, Y Chen, J Yang, L Chen, Y Du, H Walters, R Millwood, IY Dai, J Ma, H Zhang, Z Chen, Z Hu, Z Lv, J Jin, G Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank |
| title | Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank |
| title_full | Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank |
| title_fullStr | Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank |
| title_full_unstemmed | Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank |
| title_short | Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank |
| title_sort | polygenic risk scores for pan cancer risk prediction in the chinese population a population based cohort study based on the china kadoorie biobank |
| work_keys_str_mv | AT zhum polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT zhux polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT hany polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT maz polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT jic polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT wangt polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT yanc polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT songc polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT yuc polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT sund polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT jiangy polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT chenj polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT yangl polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT cheny polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT duh polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT waltersr polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT millwoodiy polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT daij polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT mah polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT zhangz polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT chenz polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT huz polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT lvj polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank AT jing polygenicriskscoresforpancancerriskpredictioninthechinesepopulationapopulationbasedcohortstudybasedonthechinakadooriebiobank |