- By FYH News Team
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doi: 10.1002/hep4.1976.
Online ahead of print.
1
2
, Brenda Diergaarde
2
3
, Allison L Kuipers
1
, Jennifer J Adibi
1
, Hung N Luu
1
2
, Xuling Chang
4
5
, Rajkumar Dorajoo
6
7
, Chew-Kiat Heng
4
5
, Chiea-Chuen Khor
6
8
, Renwei Wang
2
, Aizhen Jin
9
, Woon-Puay Koh
9
10
, Jian-Min Yuan
1
2
Affiliations
Affiliations
- 1 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- 2 UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- 3 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- 4 Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- 5 Khoo Teck Puat – National University Children’s Medical Institute, National University Health System, Singapore, Singapore.
- 6 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
- 7 Health Services and Systems Research, Duke-NUS Medical School Singapore, Singapore, Singapore.
- 8 Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
- 9 Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- 10 Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
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Claire E Thomas et al.
Hepatol Commun.
.
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doi: 10.1002/hep4.1976.
Online ahead of print.
Authors
1
2
, Brenda Diergaarde
2
3
, Allison L Kuipers
1
, Jennifer J Adibi
1
, Hung N Luu
1
2
, Xuling Chang
4
5
, Rajkumar Dorajoo
6
7
, Chew-Kiat Heng
4
5
, Chiea-Chuen Khor
6
8
, Renwei Wang
2
, Aizhen Jin
9
, Woon-Puay Koh
9
10
, Jian-Min Yuan
1
2
Affiliations
- 1 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- 2 UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- 3 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
- 4 Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- 5 Khoo Teck Puat – National University Children’s Medical Institute, National University Health System, Singapore, Singapore.
- 6 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
- 7 Health Services and Systems Research, Duke-NUS Medical School Singapore, Singapore, Singapore.
- 8 Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
- 9 Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- 10 Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
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Abstract
It is difficult to identify people with nonalcoholic fatty liver disease (NAFLD) who are at high risk for developing hepatocellular carcinoma (HCC). A polygenic risk score (PRS) for hepatic fat (HFC-PRS) derived from non-Asians has been reported to be associated with HCC risk in European populations. However, population-level data of this risk in Asian populations are lacking. Utilizing resources from 24,333 participants of the Singapore Chinese Health Study (SCHS), we examined the relationship between the HFC-PRS and HCC risk. In addition, we constructed and evaluated a NAFLD-related PRS (NAFLD-PRS) with HCC risk in the SCHS. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence with both HFC-PRS and NAFLD-PRS. The HFC-PRS and NAFLD-PRS were highly correlated (Spearman r = 0.79, p < 0.001). The highest quartiles of both the HFC-PRS and the NAFLD-PRS were associated with significantly increased risk of HCC with HR of 2.39 (95% CI 1.51, 3.78) and 1.77 (95% CI 1.15, 2.73), respectively, compared with their respective lowest quartile. Conclusion: The PRS for hepatic fat content or NAFLD may be useful for assessing HCC risk in both Asian and European populations. The findings of this and prior studies support a potential causal role of genetically determined NAFLD in HCC development.
© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
References
REFERENCES
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Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Pineros M, Anaor A, et al. Cancer statistics for the year 2020: an overview. Int J Cancer. 2021;149(4):778-89. https://doi.org/10.1002/ijc.33588. [Epub ahead of print]
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Wong S, Ting Y, Chan W. Epidemiology of non-alcoholic fatty liver disease-related hepatocellular carcinoma and its implications. JGH Open. 2018;2(5):235-41.
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Fan JG, Kim SU, Wong VWS. New trends on obesity and NAFLD in Asia. J Hepatol. 2017;67(4):862-73.
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Shen J, Wong GLH, Chan HLY, Chan HY, Yeung DKW, Chan RSM, et al. PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome. Aliment Pharmacol Ther. 2014;39(5):532-9.
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Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet. 2018;19(9):581-90.
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