Obesity, genetically elevated bilirubin and cancer risk

Grant_ FWF - Austrian Science Fund, Project No. P32303

Obesity, genetically elevated bilirubin and the cancer risk 

Funding Body: FWF-Austrian Science Fund, Project No. P32303 

Duration: 2019-2022 

Principal Investigator:

Karl-Heinz Wagner
Heinz Freisling, Co-Project leader, IARC, France

 

Main Project group:

Nazlisadat Seyed Khoei, PhD student
 

Cooperation partners:

Dr. Heinz Freisling, IARC, Lyon, 
 

Short description:

Obesity, usually marked by a high body mass index (BMI), is now an established risk factor for the development of many different cancers. However, not all obese individuals, even with the same body fat content and body fat distribution, develop these cancers.

One likely explanation is that physiological characteristics of a person such as gender, age, or genetics together with having an elevated body fat content may render an individual more or less prone to develop cancer.

One promising physiological characteristic in changing the effect of obesity on cancer is genetically elevated bilirubin. Bilirubin is an end product of the normal degradation process of red blood cells. It has long been thought that bilirubin possesses little or no physiological function, but scientific evidence has demonstrated that bilirubin actually exhibits substantial anti-inflammatory and antioxidant properties.

Mildly elevated bilirubin levels – with normal liver function tests – are generally indicative of a

condition described as Gilbert syndrome (GS), which is a common condition affecting 5-20% of the population (depending on ethnicity and gender).

Individuals with GS usually have a favorable metabolic health such as improved glucose metabolism, lower BMI, lower body fat mass, and a more efficient energy metabolism. Further, individuals with GS appear to be at lower risk for developing chronic diseases including cancer. Based on these existing data, it seems plausible that individuals with elevated bilirubin levels are less prone to develop cancers associated with obesity.

Our main aim is to compare the risk of developing obesity-related cancers between obese individuals with and without mildly elevated bilirubin levels; we will also compare these risks to normal weight individuals with and without mildly elevated bilirubin levels.

Our specific objectives are:

     

  1. To investigate associations between obesity/bilirubin defined metabolic health types and the risk of developing ‘obesity-related cancers’ combined and specifically cancers of the colorectum, breast, endometrium and pancreas;
  2.  

  3. To explore whether the favorable metabolic health of individuals with mildly elevated bilirubin levels can explain associations between obesity/bilirubin defined metabolic health types and the risk of developing ‘obesity-related cancers’ combined and those of the colorectum, breast, endometrium and pancreas;
  4.  

  5. To explore whether individuals genetically pre-disposed to both obesity (=obese genotype) and the Gilbert syndrome (=GS genotype) have a different risk of developing cancers of the colorectum, breast, endometrium and pancreas compared to individuals who have an obese genotype, but not a GS genotype.
  6.  

These studies with large international data sets will help to understand the potential of the hyperbilirubinaemic genotype to protect from obesity related Cancers.

 

ISI Publications prior to the project