Clues to the link between obesity and liver cancer-and identification of a new risk group

October 25, 2018

New research from Monash University and the Peter MacCallum Cancer Centre has found a previously overlooked group of obese people may be at risk of developing deadly liver cancer. The research, published today in Cell, has also explained how obesity is linked to liver cancer, both of which are increasing rapidly in the developing world.

In the last decade, obesity has become one of the biggest causes of cancer worldwide, and is expected to eclipse smoking. In women, obesity is a major driver of endometrial and breast cancer, whereas one of the main cancers caused by obesity in men is hepatocellular carcinoma (HCC), or liver cancer.

Liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer death. Over the last 20 years, the incidence of liver cancer has doubled in the United States (US) and tripled in Australia. The obesity epidemic accounts for 30-40 per cent of this increase in liver cancer.

Most obese individuals who develop liver cancer first develop non-alcoholic fatty liver disease (NALFD), and then the more severe non-alcoholic steatohepatitis (NASH). This can lead to cirrhosis and liver failure, and in some cases to liver cancer.

However, research by a team led by Professor Tony Tiganis, from the Monash Biomedicine Discovery Institute and Peter Mac, reveals that there are pathways to the development of liver cancer in obese people that are not reliant on the development of NASH or cirrhosis.

Current guidelines in Europe and the US restrict the testing for liver cancer in obesity to patients with cirrhosis only.

This discovery means that there is potentially a group of people who may be at risk of liver cancer who are not being screened for the disease.

"What this research has shown is that the current screening for liver cancer in obese patients is potentially missing a group of at-risk people. Until now, we have believed that the lack of development of serious liver disease has meant certain groups are unlikely to develop the deadly cancer," Professor Tiganis said.

According to Professor Tiganis, more research is needed to better understand the link between obesity and liver cancer, now that the existing assumptions have been overturned.

"If having NASH or cirrhosis are not the only pathways for the development of liver cancer in obese people, we urgently need to develop biomarkers to help identify those NAFLD patients that may be at risk of developing HCC," Professor Tiganis said.

The research used animal models and human tissue biopsies, which were provided by Professor Wendy Brown and her team from the Monash University Department of Surgery.

The research defined two separate molecular pathways for the development of NASH-cirrhosis versus liver cancer in obese mice, potentially opening the way for interventions to prevent the progression to cirrhosis or liver cancers in people with obesity.

The research reveals that the obesity-NASH-cirrhosis pathway is driven by the triggering of a protein called STAT-1. However those mice who developed liver cancer without developing NASH had their cancers triggered by a different protein, called STAT-3.

There are currently drugs available that are approved for use in other diseases that target the STAT-1 and STAT-3 pathways, however Professor Tiganis cautions that it is too early to assume that these drugs can have a beneficial impact on preventing the development of liver cancer in people who are obese.

Standard chemotherapy responses for liver cancer are poor, in most cases there is no impact on overall survival rates. Professor Tiganis believes there is an urgent need for the development of targeted therapeutics.

A 2017 report by the Centers for Disease Control and Prevention in the US revealed that in the previous decade 40 per cent of cancers were associated with obesity, overtaking smoking as the leading cause of cancer.
-end-
Read the full text in Cell titled Obesity drives STAT-1-dependent NASH and STAT-3-dependent HCC.

About the Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

About Peter Mac

Peter MacCallum Cancer Centre is one of the world's leading cancer research, education and treatment centres globally and is Australia's only public hospital solely dedicated to caring for people affected by cancer. We have over 2,500 staff, including more than 580 laboratory and clinical researchers, all focused on providing better treatments, better care and potential cures for cancer.

Media enquiries

Tania Ewing
+61 408 378 422
taniaewing@taniaewing.com

Monash University

Related Obesity Articles from Brightsurf:

11 years of data add to the evidence for using testosterone therapy to treat obesity, including as an alternative to obesity surgery
New research covering 11 years of data presented at this year's European and International Congress on Obesity (ECOICO 2020) show that, in obese men suffering from hypogonadism (low testosterone), treatment with testosterone injections lowers their weight and improves a wide range of other metabolic parameters.

Overlap between immunology of COVID-19 and obesity could explain the increased risk of death in people living with obesity, and also older patients
Data presented in a special COVID-19 session at the European and International Congress on Obesity (ECOICO 2020) suggests that there are overlaps between the immunological disturbances found in both COVID-19 disease and patients with obesity, which could explain the increased disease severity and mortality risk faced by obese patients, and also elderly patients, who are infected by the SARS-CoV-2 virus that causes COVID-19 disease.

New obesity guideline: Address root causes as foundation of obesity management
besity management should focus on outcomes that patients consider to be important, not weight loss alone, and include a holistic approach that addresses the root causes of obesity, according to a new clinical practice guideline published in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/lookup/doi/10.1503/cmaj.191707.

Changing the debate around obesity
The UK's National Health Service (NHS) needs to do more to address the ingrained stigma and discrimination faced by people with obesity, says a leading health psychologist.

Study links longer exposure to obesity and earlier development of obesity to increased risk of type 2 diabetes
Cumulative exposure to obesity could be at least as important as actually being obese in terms of risk of developing type 2 diabetes (T2D), concludes new research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]).

How much do obesity and addictions overlap?
A large analysis of personality studies has found that people with obesity behave somewhat like people with addictions to alcohol or drugs.

Should obesity be recognized as a disease?
With obesity now affecting almost a third (29%) of the population in England, and expected to rise to 35% by 2030, should we now recognize it as a disease?

Is obesity associated with risk of pediatric MS?
A single-center study of 453 children in Germany with multiple sclerosis (MS) investigated the association of obesity with pediatric MS risk and with the response of first-line therapy in children with MS.

Women with obesity prior to conception are more likely to have children with obesity
A systematic review and meta-analysis identified significantly increased odds of child obesity when mothers have obesity before conception, according to a study published June 11, 2019 in the open-access journal PLOS Medicine by Nicola Heslehurst of Newcastle University in the UK, and colleagues.

Obesity medicine association announces major updates to its adult obesity algorithm
The Obesity Medicine Association (OMA) announced the immediate availability of the 2019 OMA Adult Obesity Algorithm, with new information for clinicians including the relationship between Obesity and Cardiovascular Disease, Diabetes Mellitus, Dyslipidemia, and Cancer; information on investigational Anti-Obesity Pharmacotherapy; treatments for Lipodystrophy; and Pharmacokinetics and Obesity.

Read More: Obesity News and Obesity Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.