Xuehong Zhang

MD, ScD

The Brigham and Women's Hospital, Inc.

Associate Professor

PLCO (Learn more about this study)

PLCO-618

Apr 30, 2020

Young adulthood adiposity, weight change, and other metabolic comorbidities with the risk of hepatobiliary cancer incidence and mortality in the PLCO study

Hepatobiliary cancers, comprising of liver cancer and biliary tract cancer, are highly lethal.1 In the United States, the liver cancer incidence has tripled since 1980s, suggesting the need to investigate the underlying reason for this long-term increase. Despite a stable or decreasing trend for cancers in biliary tract, the majority of patients develop biliary tract cancer in the absence of identifiable risk factors.2 Coinciding with the increased incidence of liver cancer, we see epidemic of obesity, diabetes, hypertension, and metabolic syndrome.3, 4

Excess adult adiposity is a well-established risk factor for liver cancer, while little is known about the role of adiposity at earlier age or across the life course in the development of liver cancer, especially biliary tract cancer.5-10 Assessing adiposity in early adulthood may provide additional information on when in carcinogenesis adiposity might play a role. Weight change analysis could provide additional insights into prevention strategies targeting weight control. In addition, whether obese individuals with additional metabolic comorbidities (e.g., diabetes and hypertension) have higher risk of hepatobiliary cancer is less studied.11 Collectively, such information is important for primary hepatobiliary cancer prevention strategies. Thus, we propose to evaluate the impact of adiposity at earlier age or across the life course, adulthood weight gain, and other metabolic comorbidities including diabetes and hypertension on the risk of liver and biliary tract cancer incidence and mortality.

References

1. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States Part III: Liver, biliary tract, and pancreas. Gastroenterology 2009;136:1134-44.
2. Blechacz B. Cholangiocarcinoma: Current Knowledge and New Developments. Gut Liver 2017;11:13-26.
3. El-Serag HB, Kanwal F. Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go? Hepatology 2014;60:1767-75.
4. Singal AG, El-Serag HB. Hepatocellular Carcinoma From Epidemiology to Prevention: Translating Knowledge into Practice. Clin Gastroenterol Hepatol 2015;13:2140-51.
5. Yang B, Petrick JL, Kelly SP, et al. Adiposity across the adult life course and incidence of primary liver cancer: The NIH-AARP cohort. Int J Cancer 2017;141:271-278.
6. Schlesinger S, Aleksandrova K, Pischon T, et al. Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort. Int J Cancer 2013;132:645-57.
7. Luo J, Hendryx M, Manson JE, et al. Intentional Weight Loss and Obesity-Related Cancer Risk. JNCI Cancer Spectr 2019;3:pkz054.
8. Hagstrom H, Tynelius P, Rasmussen F. High BMI in late adolescence predicts future severe liver disease and hepatocellular carcinoma: a national, population-based cohort study in 1.2 million men. Gut 2018;67:1536-1542.
9. Hassan MM, Abdel-Wahab R, Kaseb A, et al. Obesity Early in Adulthood Increases Risk but Does Not Affect Outcomes of Hepatocellular Carcinoma. Gastroenterology 2015;149:119-29.
10. Campbell PT, Newton CC, Freedman ND, et al. Body Mass Index, Waist Circumference, Diabetes, and Risk of Liver Cancer for U.S. Adults. Cancer Res 2016;76:6076-6083.
11. Simon TG, King LY, Chong DQ, et al. Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies. Hepatology 2018;67:1797-1806.

We propose to test the following hypothesis:

1. Adiposity in young adulthood and weight again are independently associated with liver and biliary tract cancer incidence and mortality.
2. Other metabolic comorbidities including diabetes and hypertension is independently associated with liver and biliary tract cancer incidence and mortality.