Participating institutions name

and acronyms

·         INCAP Research Center for the prevention of Chronic Diseases -CIIPEC-

·         Institute of Nutrition of Central América and Panamá -INCAP-

·         Division of Epidemiology and Genetics/ National Cancer Institute -NCI-

·         Duke University, School of Engineering

·         INTEGRA Cancer Institute

INCAP/CIIPEC Researchers and/or collaborators

CIIPEC/INCAP

Manuel Ramírez MD, PhD

Fernanda Kroker, PhD

Álvaro Rivera, MD, MPH, MBA

Researchers and/or collaborators from participating institutions  

DCEG/NCI

Katherine A. McGlynn, Ph.D.

Christian S. Alvarez, Ph.D.

M. Constanza Camargo, Ph.D.

Michael Dean, PhD

INTEGRA Cancer Institute

Eduardo Gharzouzi, MD

Duke University

Dr. Ashutosh Chilkito, Ph.D.

Dr. Nelson Chao, MD, MBA

María Iglesias de Ussel, Ph.D.

Background

Liver cancer is the second leading cause of death worldwide, and in particular its dominant histological type, hepatocellular carcinoma (HCC), is one of the main contributors to the global burden of cancer. However, this type of cancer has been undergoing an epidemiological transition since the beginning of the 21st century. Some important risk factors such as hepatitis B virus (HBV) and hepatitis C virus (HCV) are decreasing in prevalence at the same time that HCC incidence rates are increasing in many countries. Understanding what risk factors are driving HCC not associated with HBV or HCV in this new era will be important to face the challenge of increasing incidence and mortality rates.

Northern Central America, one of the three regions in the world with the highest HCC rates, appears to be dominated by non-viral HCC, unlike other regions with high HCC rates in Asia and Africa.Northern Central America offers a unique opportunity to begin to obtain clues in the etiology of this cancer; given that the epidemiological profile indicates that HCC cases not associated with HBV or HCV are increasing. However, there have been no previous epidemiological investigations of HCC in the region. To fill this gap, preliminary studies have been carried out by our research group in Guatemala since 2016; and several interesting hypotheses have been put forward. For example, high rates of metabolic disorders (obesity, diabetes, fatty liver disease) and elevated levels of aflatoxins are emerging as important factors. However, we speculate that these factors alone are unlikely to drive the incidence of HCC as high as it occurs in the region. Other factors, including other mycotoxin exposures, Helicobacter pylori (H. pylori), exposure to microcystins, use of herbal medications, and exposure to pesticides, may also play an important role in contributing to increased risk.

General objective

The primary objective of this study is to identify environmental risk factors for HCC in Guatemala such as exposure to mycotoxins, history of H. pylori, use of herbal supplements, water contaminated with microcystins, aflatoxins, fatty liver disease, exposure to pesticides, alcohol consumption and tobacco use. A secondary objective of this study is to validate new technologies that allow early detection of HCC.

Methodology

To examine these and other hypotheses, it is proposed to carry out an HCC case-control study of 500 cases and 1000 controls paired by frequency of age and sex. All participants will be users of the national public health system of the Ministry of Public Health and Social Assistance and will be residents of the department of Guatemala and 4 other surrounding departments. The study will provide an opportunity to compare cases with controls. In addition, we will conduct a sub-study to compare controls with and without fatty liver disease. Finally, we will validate a new screening technology among a subgroup of cases and controls. We anticipate that this study will increase our understanding of the etiology of HCC. This knowledge can be useful not only for the Central American region whose HCC rate is high, but also for many other regions. Our findings may be of particular relevance to the U.S., where Hispanics are the largest minority group, have the highest prevalence of fatty liver disease, and this group is projected to have the highest incidence of HCC in the country in the next decade.

Study duration

3.5 years

Status

Currently Recruiting