TY - JOUR
T1 - Risk stratification for hepatocellular cancer among patients with cirrhosis using a hepatic fat polygenic risk score
AU - Thrift, Aaron P.
AU - Kanwal, Fasiha
AU - Liu, Yanhong
AU - Khaderi, Saira
AU - Singal, Amit G.
AU - Marrero, Jorge A
AU - Loo, Nicole
AU - Asrani, Sumeet K.
AU - Luster, Michelle
AU - Al-Sarraj, Abeer
AU - Ning, Jing
AU - Tsavachidis, Spiridon
AU - Gu, Xiangjun
AU - Amos, Christopher I.
AU - El-Serag, Hashem B.
N1 - Funding Information:
This work was supported by the National Cancer Institute (NCI U01 CA23099, U01 CA230694, P01 CA263025, and R01 CA186566), Cancer Prevention & Research Institute of Texas grants (RP150587, RP220119 and RP200537), and in part by Center for Gastrointestinal Development, Infection and Injury (NIDDK P30 DK 56338). Drs. Kanwal and El-Serag are investigators at the Veterans Administration Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413), Michael E. DeBakey VA Medical Center, Houston, Texas. Patient DNA samples were stored and processed at the Population Sciences Biorepository core at Baylor College of Medicine with funding from the NCI (P30 Cancer Center Support Grant CA125123). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2023 Thrift et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2023/2
Y1 - 2023/2
N2 - Background Polygenic risk scores (PRS) hold the promise to refine prognostication in hepatocellular cancer (HCC). The few available HCC PRS include germline risk variants identified among individuals of mostly European ancestry, but data are lacking on the transportability of these PRS in multiethnic U.S patients with cirrhosis from multiple etiologies. Methods We used data from 1644 patients with cirrhosis enrolled in two prospective cohort studies in the U.S. Patients were followed until HCC diagnosis, death, liver transplantation, or last study visit through June 30, 2021. The high-risk variants in PNPLA3-MBOAT7-TM6SF2-GCKR were combined in a PRS and we evaluated its association with HCC. Discriminatory accuracy was assessed using the C-statistic. Results During 4,759 person-years of follow-up, 93 patients developed HCC. Mean age was 59.8 years, 68.6% were male, 27.2% Hispanic, 25.1% non-Hispanic Black, 25.7% had NAFLD, 42.1% had heavy alcohol use, and 19.5% had active HCV. HCC risk increased by 134% per unit increase in PRS (HR = 2.30; 95% CI, 1.35–3.92). Compared to cirrhosis patients in the lowest tertile of the PRS, those in the highest tertile had 2-fold higher risk of HCC (HR = 2.05; 95% CI, 1.22–3.44). The PRS alone had modest discriminatory ability (C-statistic = 0.58; 95% CI, 0.52–0.63); however, adding PRS to a predictive model with traditional HCC risk factors had a C-statistic of 0.70 (95% CI, 0.64–0.76), increasing from 0.68 without the PRS (p = 0.0012). Conclusions Our findings suggest that PRS may enhance risk prediction for HCC in contemporary U.S. cirrhosis patients.
AB - Background Polygenic risk scores (PRS) hold the promise to refine prognostication in hepatocellular cancer (HCC). The few available HCC PRS include germline risk variants identified among individuals of mostly European ancestry, but data are lacking on the transportability of these PRS in multiethnic U.S patients with cirrhosis from multiple etiologies. Methods We used data from 1644 patients with cirrhosis enrolled in two prospective cohort studies in the U.S. Patients were followed until HCC diagnosis, death, liver transplantation, or last study visit through June 30, 2021. The high-risk variants in PNPLA3-MBOAT7-TM6SF2-GCKR were combined in a PRS and we evaluated its association with HCC. Discriminatory accuracy was assessed using the C-statistic. Results During 4,759 person-years of follow-up, 93 patients developed HCC. Mean age was 59.8 years, 68.6% were male, 27.2% Hispanic, 25.1% non-Hispanic Black, 25.7% had NAFLD, 42.1% had heavy alcohol use, and 19.5% had active HCV. HCC risk increased by 134% per unit increase in PRS (HR = 2.30; 95% CI, 1.35–3.92). Compared to cirrhosis patients in the lowest tertile of the PRS, those in the highest tertile had 2-fold higher risk of HCC (HR = 2.05; 95% CI, 1.22–3.44). The PRS alone had modest discriminatory ability (C-statistic = 0.58; 95% CI, 0.52–0.63); however, adding PRS to a predictive model with traditional HCC risk factors had a C-statistic of 0.70 (95% CI, 0.64–0.76), increasing from 0.68 without the PRS (p = 0.0012). Conclusions Our findings suggest that PRS may enhance risk prediction for HCC in contemporary U.S. cirrhosis patients.
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U2 - 10.1371/journal.pone.0282309
DO - 10.1371/journal.pone.0282309
M3 - Article
C2 - 36854015
AN - SCOPUS:85149153750
SN - 1932-6203
VL - 18
JO - PloS one
JF - PloS one
IS - 2 February
M1 - e0282309
ER -