Genome-wide meta-analysis identifies nine loci associated with higher risk of hepatocellular carcinoma development.
메타분석
1/5 보강
PICO 자동 추출 (휴리스틱, conf 2/4)
유사 논문P · Population 대상 환자/모집단
540 cases and 2,096,759 controls, we identified 10 associations with HCC, of which five (in , , , , and ) have not previously been implicated in HCC at genome-wide statistical significance.
I · Intervention 중재 / 시술
추출되지 않음
C · Comparison 대조 / 비교
추출되지 않음
O · Outcome 결과 / 결론
We found strong correlations between genetic effects on HCC and hepatic steatosis (r = 0.
[BACKGROUND & AIMS] The genetic underpinnings of hepatocellular carcinoma (HCC) remain largely unknown.
- 연구 설계 meta-analysis
APA
Ghouse J, Gellert-Kristensen H, et al. (2025). Genome-wide meta-analysis identifies nine loci associated with higher risk of hepatocellular carcinoma development.. JHEP reports : innovation in hepatology, 7(9), 101485. https://doi.org/10.1016/j.jhepr.2025.101485
MLA
Ghouse J, et al.. "Genome-wide meta-analysis identifies nine loci associated with higher risk of hepatocellular carcinoma development.." JHEP reports : innovation in hepatology, vol. 7, no. 9, 2025, pp. 101485.
PMID
40823170
Abstract
[BACKGROUND & AIMS] The genetic underpinnings of hepatocellular carcinoma (HCC) remain largely unknown. Thus, we aimed to identify new genetic risk loci for HCC.
[METHODS] We performed a genome-wide association study (GWAS) meta-analysis of 11 cohorts with validation in two independent cohorts. The identified variants were tested for effects on other hepatobiliary endpoints, and on incident HCC stratified by underlying risk factors. Mendelian randomization was used to assess the causal effects of a range of traits on the risk of HCC.
[RESULTS] In meta-analyses totaling 6,540 cases and 2,096,759 controls, we identified 10 associations with HCC, of which five (in , , , , and ) have not previously been implicated in HCC at genome-wide statistical significance. Known associations in , , , , and were confirmed. All associations except were validated in independent cohorts totaling 7,630 cases and 733,689 controls. The largest per-allele effect was seen for (beta = 0.61) followed by (0.55), (0.45), (0.31), (0.27), , , and (all 0.21), and (0.17). The identified variants had comparable effects on incident HCC in individuals with prevalent obesity, a high alcohol intake, diabetes, or cirrhosis. Mendelian randomization analyses confirmed the causal role of obesity in HCC. We found strong correlations between genetic effects on HCC and hepatic steatosis (r = 0.75), and HCC and cirrhosis (r = 0.69), whereas only three loci (, , and ) had concordant effects on HCC and biliary tract cancer.
[CONCLUSIONS] We identified and validated nine genetic variants associated with an increased risk of HCC development.
[IMPACT AND IMPLICATIONS] The genetic underpinnings of HCC remain largely unknown. In this genome-wide association meta-analysis totaling 6,540 cases with HCC and 2.1 million controls, we identified and validated nine genetic loci to associate with the risk of HCC. A deeper insight into genetic factors that affect the risk of HCC could improve our ability to predict and ultimately prevent or treat this deadly cancer.
[METHODS] We performed a genome-wide association study (GWAS) meta-analysis of 11 cohorts with validation in two independent cohorts. The identified variants were tested for effects on other hepatobiliary endpoints, and on incident HCC stratified by underlying risk factors. Mendelian randomization was used to assess the causal effects of a range of traits on the risk of HCC.
[RESULTS] In meta-analyses totaling 6,540 cases and 2,096,759 controls, we identified 10 associations with HCC, of which five (in , , , , and ) have not previously been implicated in HCC at genome-wide statistical significance. Known associations in , , , , and were confirmed. All associations except were validated in independent cohorts totaling 7,630 cases and 733,689 controls. The largest per-allele effect was seen for (beta = 0.61) followed by (0.55), (0.45), (0.31), (0.27), , , and (all 0.21), and (0.17). The identified variants had comparable effects on incident HCC in individuals with prevalent obesity, a high alcohol intake, diabetes, or cirrhosis. Mendelian randomization analyses confirmed the causal role of obesity in HCC. We found strong correlations between genetic effects on HCC and hepatic steatosis (r = 0.75), and HCC and cirrhosis (r = 0.69), whereas only three loci (, , and ) had concordant effects on HCC and biliary tract cancer.
[CONCLUSIONS] We identified and validated nine genetic variants associated with an increased risk of HCC development.
[IMPACT AND IMPLICATIONS] The genetic underpinnings of HCC remain largely unknown. In this genome-wide association meta-analysis totaling 6,540 cases with HCC and 2.1 million controls, we identified and validated nine genetic loci to associate with the risk of HCC. A deeper insight into genetic factors that affect the risk of HCC could improve our ability to predict and ultimately prevent or treat this deadly cancer.