Katherine McGlynn

Ph.D., M.P.H.

National Cancer Institute

Senior Investigator

PLCO (Learn more about this study)

2017-1021

Apr 12, 2018

Mechanisms of obesity in liver cancer development

Primary liver cancer has been among the most rapidly increasing cancer types in the US and other Western countries. Obesity is known to increase the risk of liver cancer, but the mechanisms underlying the association remain poorly understood. Thus, we aim to examine the pathways that are hypothesized to mediate the association between obesity and liver cancer: metabolic, lipidomic, and leaky gut. Metabolomics is the study of small molecules in the body, and certain metabolic profiles have been associated with obesity., Thus far, only one published population-based study has examined the association between metabolites and liver cancer. that study did not use state-of-the-art technology to assess metabolites. Lipidomics provides a snapshot of the pathways and networks associated with lipid metabolism, trafficking, and homeostasis. Thus far, no studies have published the results of lipidomics study ofliver cancer. Finally, biomarkers of bacterial translocation (i.e., lipopolysaccharide-binding protein, soluble CD14, antibodies against lipopolysaccharide and flagellin, and bile acids) provide a snapshot of circulating biomarkers related to gut permeability and the microbiome. However, few studies to date have investigated this association.

In order to study the etiology of liver cancer using a prospective design, the Liver Cancer Pooling Project (LCPP), a project within the NCI Cohort Consortium, was initiated in 2009. Fourteen US-based cohorts are contributing questionnaire data and serum samples to the LCPP. Questionnaire data from PLCO participants, as well as serum for HBV/HCV and sex steroid hormones, have already been approved for this consortia effort. While known risk factors, such as HBV/HCV alcohol consumption, have been studied extensively, an examination of other obesity-related factors, might greatly enhance the current understanding of the etiology of liver cancer in the US. Thus, this application will seek to obtain serum samples from PLCO participants who developed liver cancer and from matched controls. With serum samples from 89 liver cancer cases, PLCO is the second largest cohort with serum in the pooling project.

The proposed study will leverage cutting-edge technologies and statistical techniques to investigate these pathways and their associations with liver cancer to determine if these pathways interact with, or mediate, the association between obesity and liver cancer. Specifically, this study will build on US cohorts to investigate this association, as obesity is becoming an increasing important risk factor for liver cancer in the US. Determination of these associations will provide new evidence to elucidate how obesity is affecting risk of liver cancer.