Skip to main content

COVID-19 is an emerging, rapidly evolving situation.

What people with cancer should know:

Guidance for cancer researchers:

Get the latest public health information from CDC:

Get the latest research information from NIH:

Grant Details

Grant Number: 5R01CA186566-05 Interpret this number
Primary Investigator: Hassan, Manal
Organization: University Of Tx Md Anderson Can Ctr
Project Title: Genome-Wide Association Study (GWAS) in Hepatocellular Carcinoma (HCC)
Fiscal Year: 2019


DESCRIPTION (provided by applicant): Over the past 30 years, the incidence of hepatocellular carcinoma (HCC) in the United States has tripled. Chronic hepatitis C virus (HCV) infection has been the major underlying reason for this increase. However, only a small fraction of chronic HCV carriers develop HCC. Variation in the risk of HCC among chronic HCV carriers may be caused by complex interplay between genetic and environmental factors. Several studies indicate a positive association between history of liver cancer in first-degree relatives and risk of HCC development, supporting the potential impact of genetic factors in HCC development. The mechanisms of HCV-induced HCC and genetic susceptibility factors for HCC in chronic HCV carriers are not well studied. Candidate gene-based association studies have implicated a few genetic variants in HCC etiology, but none have been validated as meaningful genetic factors for HCV-associated HCC in the U.S. or for clinical outcomes of HCC. We hypothesize that unique host genetic factors can predict HCC risk in non-viral cases, whereas other markers may predict HCC development in patients with chronic HCV infection and clinical outcome in HCC, including response to therapy. The recent explosion of genome-wide association studies (GWASs) has identified numerous genetic susceptibility loci for many cancers. To date, however, no HCC GWAS has been published in the U.S., in part because of difficulty in recruiting large numbers of HCC patients, a result of HCC's natural history and clinical features: 1) HCC is uncommon, especially in the U.S.; 2) HCC is typically diagnosed at a late stage with poor survival; and 3) end- stage chronic liver disease is a major underlying burden in HCC patients. Another barrier to genetic studies of HCC is the lack of comprehensive data on epidemiological and environmental risk factors to control for confounding effects. Only through multi-institutional collaboration can a GWAS of an uncommon cancer such as HCC be performed in the U.S. We propose a GWAS of HCC using 19 North American institutions, which will enable the integration of genetic, environmental, and clinical data. A total of 1715 HCC cases and 3254 controls will be included in the discovery phase, and results will be validated in 2410 cases and 4420 controls. All cases will be frequency-matched to control subjects by age, race and sex. The impact of the validated genotypes on the incidence of HCC development will be assessed in 1100 patients with cirrhosis and who are under surveillance for the development of HCC and enrolled in an NCI-funded follow-up study. In addition to risk assessment, the effect of genetic variation on overall survival of HCC patients will be determined in all cases including an exploratory analysis of progression free survival in HCC patients who have been treated with sorafenib, the current standard of care for advanced HCC. Finally, we plan to explore our objective in Hispanics, Blacks, and Asians for future minority-specific genetic studies in U.S. Our GWAS will provide a detailed understanding of the genetic risk factors for HCC development and prognosis in the U.S.


Effect of Statins on the Risk of Extrahepatic Cholangiocarcinoma.
Authors: Lavu S. , Therneau T.M. , Harmsen W.S. , Mara K.C. , Wongjarupong N. , Hassan M. , Ali H.A. , Antwi S. , Giama N.H. , Miyabe K. , et al. .
Source: Hepatology (Baltimore, Md.), 2020 Oct; 72(4), p. 1298-1309.
EPub date: 2020-10-09.
PMID: 32119126
Related Citations

HepatoScore-14: Measures of biological heterogeneity significantly improve prediction of hepatocellular carcinoma risk.
Authors: Morris J.S. , Hassan M.M. , Zohner Y.E. , Wang Z. , Xiao L. , Rashid A. , Haque A. , Abdel-Wahab R. , Mohamed Y.I. , Ballard K.L. , et al. .
Source: Hepatology (Baltimore, Md.), 2020-09-15; , .
EPub date: 2020-09-15.
PMID: 32931023
Related Citations

Lymphocyte to monocyte ratio-based nomogram for predicting outcomes of hepatocellular carcinoma treated with sorafenib.
Authors: Ha Y. , Mohamed Ali M.A. , Petersen M.M. , Harmsen W.S. , Therneau T.M. , Lee H.C. , Ryoo B.Y. , Bampoh S. , Valles K.A. , Mady M. , et al. .
Source: Hepatology international, 2020 Sep; 14(5), p. 776-787.
EPub date: 2020-08-01.
PMID: 32740886
Related Citations

Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease.
Authors: Yang J.D. , Ahmed F. , Mara K.C. , Addissie B.D. , Allen A.M. , Gores G.J. , Roberts L.R. .
Source: Hepatology (Baltimore, Md.), 2020 03; 71(3), p. 907-916.
EPub date: 2019-10-21.
PMID: 31309602
Related Citations

Penetrance of Different Cancer Types in Families with Li-Fraumeni Syndrome: A Validation Study Using Multicenter Cohorts.
Authors: Shin S.J. , Dodd-Eaton E.B. , Peng G. , Bojadzieva J. , Chen J. , Amos C.I. , Frone M.N. , Khincha P.P. , Mai P.L. , Savage S.A. , et al. .
Source: Cancer research, 2020-01-15; 80(2), p. 354-360.
EPub date: 2019-11-12.
PMID: 31719101
Related Citations

Penetrance Estimates Over Time to First and Second Primary Cancer Diagnosis in Families with Li-Fraumeni Syndrome: A Single Institution Perspective.
Authors: Shin S.J. , Dodd-Eaton E.B. , Gao F. , Bojadzieva J. , Chen J. , Kong X. , Amos C.I. , Ning J. , Strong L.C. , Wang W. .
Source: Cancer research, 2020-01-15; 80(2), p. 347-353.
EPub date: 2019-11-12.
PMID: 31719099
Related Citations

Risk of De Novo Hepatocellular Carcinoma Following Use of Direct Acting Antiviral Medications for Treatment of Chronic Hepatitis C.
Authors: Antwi S.O. , Van Houten H.K. , Sangaralingham L.R. , Patel T. .
Source: Cancer prevention research (Philadelphia, Pa.), 2019 12; 12(12), p. 891-902.
EPub date: 2019-08-26.
PMID: 31451519
Related Citations

A global view of hepatocellular carcinoma: trends, risk, prevention and management.
Authors: Yang J.D. , Hainaut P. , Gores G.J. , Amadou A. , Plymoth A. , Roberts L.R. .
Source: Nature reviews. Gastroenterology & hepatology, 2019 10; 16(10), p. 589-604.
EPub date: 2019-08-22.
PMID: 31439937
Related Citations

A machine learning model to predict hepatocellular carcinoma response to transcatheter arterial chemoembolization.
Authors: Morshid A. , Elsayes K.M. , Khalaf A.M. , Elmohr M.M. , Yu J. , Kaseb A.O. , Hassan M. , Mahvash A. , Wang Z. , Hazle J.D. , et al. .
Source: Radiology. Artificial intelligence, 2019 Sep; 1(5), .
EPub date: 2019-09-25.
PMID: 31858078
Related Citations

Genomic Medicine and Implications for Hepatocellular Carcinoma Prevention and Therapy.
Authors: Dhanasekaran R. , Nault J.C. , Roberts L.R. , Zucman-Rossi J. .
Source: Gastroenterology, 2019 01; 156(2), p. 492-509.
EPub date: 2018-11-04.
PMID: 30404026
Related Citations

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma.
Authors: Hassan M.M. , Botrus G. , Abdel-Wahab R. , Wolff R.A. , Li D. , Tweardy D. , Phan A.T. , Hawk E. , Javle M. , Lee J.S. , et al. .
Source: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2017 Nov; 15(11), p. 1791-1799.
EPub date: 2017-06-01.
PMID: 28579181
Related Citations

Opportunities and Challenges for Environmental Exposure Assessment in Population-Based Studies.
Authors: Patel C.J. , Kerr J. , Thomas D.C. , Mukherjee B. , Ritz B. , Chatterjee N. , Jankowska M. , Madan J. , Karagas M.R. , McAllister K.A. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2017 09; 26(9), p. 1370-1380.
EPub date: 2017-07-14.
PMID: 28710076
Related Citations

A Novel Pathway-Based Approach Improves Lung Cancer Risk Prediction Using Germline Genetic Variations.
Authors: Qian D.C. , Han Y. , Byun J. , Shin H.R. , Hung R.J. , McLaughlin J.R. , Landi M.T. , Seminara D. , Amos C.I. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016 08; 25(8), p. 1208-15.
EPub date: 2016-05-24.
PMID: 27222311
Related Citations

FastPop: a rapid principal component derived method to infer intercontinental ancestry using genetic data.
Authors: Li Y. , Byun J. , Cai G. , Xiao X. , Han Y. , Cornelis O. , Dinulos J.E. , Dennis J. , Easton D. , Gorlov I. , et al. .
Source: BMC bioinformatics, 2016-03-09; 17, p. 122.
EPub date: 2016-03-09.
PMID: 26961892
Related Citations

Clinical implications of basic research in hepatocellular carcinoma.
Authors: Dhanasekaran R. , Venkatesh S.K. , Torbenson M.S. , Roberts L.R. .
Source: Journal of hepatology, 2016 Mar; 64(3), p. 736-45.
EPub date: 2015-10-09.
PMID: 26450813
Related Citations

Independent and Joint Use of Statins and Metformin by Elderly Patients With Diabetes and Overall Survival Following HCC Diagnosis.
Authors: Antwi S.O. , Li Z. , Mody K. , Roberts L.R. , Patel T. .
Source: Journal of clinical gastroenterology, 2020 May/Jun; 54(5), p. 468-476.
PMID: 32271517
Related Citations

Back to Top