Obesity increases cancer risk over generations

Researchers identified a microRNA in obese female mice that transmit a potential risk of liver cancer to their offspring over generations.

MicroRNA may be a possible risk marker for liver cancer

Researchers identified a microRNA in obese female mice that transmit a potential risk of liver cancer to their offspring over generations.

Like a small "infectious" agent, a particular microRNA seems to transfer the risk of liver cancer from an obese mother to her offspring, and further generations. This is what study data from a mouse model has suggested. These data may also be of great relevance to humans.

A look at the obesity-epidemic in humans

More than a third of all people in the world today are overweight or even obese. In many industrialized nations, this indicator may go up to one in two. Obesity is also the main cause of non-alcoholic fatty liver and liver carcinoma.

A possible "transferability" of the liver cancer risk from obese patients to their children and grandchildren would indeed be very important for the control of the current obesity epidemic.

miR-27a-3p as a trigger and information carrier

In their mouse model, the researchers used diethylnitrosamine (DEN) to trigger liver carcinomas in obese mice. The mice were first fed a high-calorie, high-fat diet. The researchers used RNA sequencing in the mice mothers and their offspring to find out which genes and microRNAs had changed over generations. 

The most outstanding result of the study indicated that when pregnant mice received an injection of "miR-27a-3p" microRNA, the expression of miR-27a-3p in the liver increased in their offspring; while the expression of two genes, Acsl1 and Aldh2, decreased. If the offspring "altered" in this way received a DEN injection, they developed hepatocellular carcinomas (HCC) at a higher rate.

Furthermore, it was observed that the microRNA effect can continue and even increase over generations. For example, mice from an obese mother and grandmother generation had a significantly higher rate of hepatocellular carcinoma than those with an obese mother but normal-weight grandmother.

Implications for medical practice

The study data from the mouse model show possible relationships between the nutritional status of mothers and their offspring and a possible risk of hepatocellular carcinoma. It has also been known for some time that metabolic diseases and the risk of obesity are epigenetically mapped and can also influence future generations. Therefore, according to the authors, it is important for physicians to be more attentive to obesity and pregnancy advice for their patients and to provide nutritional medical support to affected women. 

Sun Y et al., Multigenerational maternal obesity increases the incidence of HCC in offspring via miR-27a-3p Journal of Hepatology 2020; 73(3): https://doi.org/10.1016/j.jhep.2020.03.050