In:
International Journal of Cancer, Wiley, Vol. 151, No. 10 ( 2022-11-15), p. 1726-1736
Kurzfassung:
Several polygenic risk scores (PRSs) have been developed to predict the risk of colorectal cancer (CRC) in European descendants. We used genome‐wide association study (GWAS) data from 22 702 cases and 212 486 controls of Asian ancestry to develop PRSs and validated them in two case‐control studies (1454 Korean and 1736 Chinese). Eleven PRSs were derived using three approaches: GWAS‐identified CRC risk SNPs, CRC risk variants identified through fine‐mapping of known risk loci and genome‐wide risk prediction algorithms. Logistic regression was used to estimate odds ratios (ORs) and area under the curve (AUC). PRS 115‐EAS , a PRS with 115 GWAS‐reported risk variants derived from East‐Asian data, validated significantly better than PRS 115‐EUR derived from European descendants. In the Korea validation set, OR per SD increase of PRS 115‐EAS was 1.63 (95% CI = 1.46‐1.82; AUC = 0.63), compared with OR of 1.44 (95% CI = 1.29‐1.60, AUC = 0.60) for PRS 115‐EUR . PRS 115‐EAS/EUR derived using meta‐analysis results of both populations slightly improved the AUC to 0.64. Similar but weaker associations were found in the China validation set. Individuals among the highest 5% of PRS 115‐EAS/EUR have a 2.52‐fold elevated CRC risk compared with the medium (41‐60th) risk group and have a 12% to 20% risk of developing CRC by age 85. PRSs constructed using results from fine‐mapping and genome‐wide algorithms did not perform as well as PRS 115‐EAS and PRS 115‐EAS/EUR in risk prediction, possibly due to a small sample size. Our results indicate that CRC PRSs are promising in predicting CRC risk in East Asians and highlights the importance of using population‐specific data to build CRC risk prediction models.
Materialart:
Online-Ressource
ISSN:
0020-7136
,
1097-0215
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2022
ZDB Id:
218257-9
ZDB Id:
1474822-8
