Manal M. Hassan (MB, ChB , MPH, PhD)

Associate Professor

GI Medical Oncology

UT M.D. Anderson Cancer Center

Houston, TX

HCCEC

May 6th 2013

Supported by: NCI (Hassan, Manal; El Serag, Hashem) Rare GI Cancers infrastructure fund (Phan, Aexandria)

• Rare type of Cancer in USA “ A condition which affect less than 200,000 patients in the USA”

• Incidence is increasing in USA with racial variation • Causal relationship between HCV, HBV and HCC

• Most of the epidemiological research originated from

international studies

• In USA 20-50% of the US patients are not caused by HCV or HBV

• Complicated natural history with underlying CLD and poor prognosis

• Poor prevention and screening strategy

• Limited descriptive data and epidemiological studies in USA • Lack of integration of epidemiological/ basic science / and

clinical data (Translational Research) • Lack of understanding the biological and physiological process

of the environmental risk factors • Limited information about hepato-carcinogensis in human

• Small sample size achieved by a single-cancer center • Rapid fatality and difficulty in fast case ascertainment • Lack of standardized research tool or core questionnaire

• Difficulty in getting bio-specimens and high cost of prospective data

collection • Lack of organized network and collaboration between medical centers or

between different disciplines

• Low public awareness about HCC and its associated risk factors • Lack of funding funded studies are not representative of USA

• Communication and coordination with the government (NIH and CDC)

• Identify key investigators in the field (AASLD, GI ASCO, NCI, SWOG)

• Coordination of the available resources between US centers

• Involvement of private organizations

• Learn from the experience of investigators in other cancers

• Building a new consortium and communicate with existing consortia

• Enhance the collaboration between USA centers to conduct multidisciplinary research

• Develop standardized protocols for epidemiological

studies in different USA centers e.g. questionnaires, database, and guideline for specimen collection

• Exchange research ideas related to HCC with the goal of proposing a joint grant proposal that focus on different research topics e.g. molecular epidemiology

• The outcome is joint projects, grants and publications

September 10, 2011: Announcement of EGRP-Supported Epidemiology Consortia: “http://epi.grants.cancer.gov/Consortia/entire_alpha.html “. The objective of our application is to request support for a “Meeting on Epidemiology of Hepatocellular Carcinoma (HCC) in the United States.

September 22, 2011: Communication with NCI [Senior Scientist and

Consortia Coordinator] October 28, 2011: Submission of full application

January 6, 2012: No enough funding May 15, 2012: Reapply for funding

August 14, 2012: HCC Consortium on the EGRP website:

http://epi.grants.cancer.gov/Consortia/single/hcc.html November 4, 2012: NCI request some modification in the application

December 31, 2012: Review of the revised application

February 22, 2013: NCI Approval and notification

1.Rational of the Consortium

2. Unique Question of the Consortium

3. Structure of the Consortium & Members

• Increased incidence with the fastest growing cancer-related death rate

• The Epidemiology of HCC is poorly examined and funded in USA

• Limited Publication in HCC Epidemiology from USA

PubMed reveals 3105 articles over Past 20 years 4.7% are related to HCC Epidemiology <1% from USA PubMed reveals 532 articles genetic susceptibility to

HCChttp://genetmed.fudan.edu.cn/dbHCCvar/ prior to 2011 Most published studies were conducted in Asian

populations and only one study of 48 HCC cases was published in US population.

0

500000

1000000

1500000

2000000

2500000

3000000

3500000

4000000

4500000

USA 864000 295000 304000 273000 232000 238000 0 0 0 0 0 141000 1271082

Non_USA 2064013 2140161 2542506 3820123 2453435 1760454 594000 1300374 688648 308000 297351 790602 1561412

1998 1999 2000 `2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

USA: $ 3,618082 Non-USA: $20,321139

Use the resources of an existing HCC case-control study at MD Anderson with other USA centers to develop large multicenter case-control study between USA hospitals aimed at assessing:

1. Major environmental HCC risk factors in USA 2. Genetic susceptibility of HCC risk in USA 3. Genetic susceptibility of HCV-disease progression 4. Predictors of HCC clinical outcome

May 2012: Discuss the concept of collaboration between MD Anderson, Mayo Clinic and Baylor

June 2012: Conference call with CIDR program director

July 2012: Communication with NCI

August 2012: Brief Concept of GWAS submitted to NCI

September 2012: Approval of NCI to submit full CIDR application

November 2012: Complete multi-PI submission of application

January 2013: Very good review

The Center for Inherited Disease Research (CIDR)

Aims

1. SNP Discovery related to HCC risk in non-HCV-related HCC (1113 HCC cases and 2100 normal controls)

2. SNP Discovery related to HCC risk in HCV-related HCC (387 HCC cases and 900 patients with HCV infection without HCC)

3. SNP Discovery related to HCC prognosis including overall survival and sorafenib PFS in 1500 HCC patients

Institutions and Leaders of CIDR Application

Mayo Clinic Dr. Lewis Roberts Dr. Gloria Petersen Baylor College of Medicine (Houston VA Hospital) Dr. Hashem El- Serag Dartmouth-Hitchcock Norris Cotton Cancer Center (NCCC) Dr. Christopher Amos MD Anderson Cancer Center Dr. Manal Hassan Dr. Donghui Li Dr. Ahmed Kaseb

1.Rational of the Consortium

2. Unique Question of the Consortium

3. Structure of the Consortium and Members

Sites with active HCC research program involving USA patients

Multidisciplinary membership hepatologists, oncologists, epidemiologists, biostatisticians, basic scientists

Steering committee

Policies for data sharing, biological sample exchange, authorship in publications

Continue this activity every year

Plan collaboration through joint publications and grant proposal submission

Propose an HCC GWAS validation phase

Develop a website for the consortium

Include other sites from the USA, South America, Europe, Middle East, and Asia

Learn about existing and potential resources and investigators (individual site presentations)

Standardize collecting epidemiological and clinical data

Discuss guidelines for data collection and entry, biological sample collection, DNA isolation, and storage

CIDR approved application to perform discovery phase of HCC GWAS in 1500 HCC and 3000 Controls

NIH-R01 will be submitted in June 2013 for the validation phase in independent populations from MD Anderson, Mayo, Baylor and potentially other institutions

Identify participating centers with existing HCC resources for the R01 application

Solicit new ideas for collaborative research

Advance the science in HCC and help in preventing and curing a devastating cancer

Have access to a resource with a unified HCC epidemiological and clinical database

Participate in the GWAS investigation Team of the proposed R01 receive complete genotype profile of your HCC cases and

controls Coauthor publications related to GWAS analysis

Exchange, propose new ideas for future researches using the

existing resources

Direct the future of the consortium (steering, publication committees)

Beasley was the Ashbel Smith Professor of Epidemiology at The University of Texas School of Public Health, a part of The University of Texas Health Science Center at Houston. He also served as dean of the School of Public Health from 1987 to 2005. In establishing the causative link between hepatitis B and liver cancer, Beasley was responsible for the first discovery of a virus that leads to a human cancer. His subsequent work determining the means of transmission for the virus and testing the vaccine has dramatically reduced worldwide suffering from Hepatitis B related liver disease. He was 76 at the time of his death. He died on August 25 in Houston from advanced pancreatic cancer.