Genetic links between type 2 diabetes and multiple cancers discovered in new research

Cancer is now the leading cause of death among people with diabetes in England². Figures from 2018 show 28 percent of deaths in people with diabetes in England were due to cancer, up from 22 percent in 2001, with cancer survival rates in those with diabetes lagging behind the general population. Type 2 diabetes can put people at increased risk of developing a range of serious health complications, including certain types of cancer, however the biological factors that contribute to the link between type 2 diabetes and cancer have been poorly understood. 

Type 2 diabetes is a complex condition that is influenced by a mix of drivers, including age, bodyweight and genetics. Hundreds of different genetic variants have been identified as playing a role in the development of type 2 diabetes. Likewise, some genetic variants increase the chances of getting cancer.

Researchers led by Professor Inga Prokopenko at the University of Surrey sought to uncover if relationships between the conditions at the genetic level could help to explain why some people with type 2 diabetes also get cancer. They focused on three cancer types that people with type 2 diabetes are at higher risk of developing – postmenopausal breast cancer, colorectal cancer and pancreatic cancer. 

The research team looked at DNA data from over 36,000 individuals from several European countries. This included people living with type 2 diabetes and breast, colorectal, and pancreatic cancer. The researchers pioneered a new approach that allowed them to study how genetic variants simultaneously affect all four different health conditions³.

For the first time, two specific genetic variants were pinpointed as key contributors to people developing both type 2 diabetes and some cancers. One variant was linked to the risk of developing both breast cancer and type 2 diabetes, while the other affected type 2 diabetes and breast, colorectal, and pancreatic cancer risk.  Therefore, people carrying either of these genetic variants will have an increased susceptibility to developing both type 2 diabetes and these cancers.

Other genetic variants previously identified as playing a role in type 2 diabetes and/or cancer were also examined by the researchers using their new, innovative analytical technique. They identified 17 variants that directly increase the risk of developing type 2 diabetes, and then, via biological processes linked to type 2 diabetes, indirectly increase cancer risk. It is thought this is because type 2 diabetes can create an environment in the body that makes it easier for cancer to develop and grow, through higher blood sugar levels, higher insulin levels, obesity, inflammation and hormonal changes. 

The findings illuminate previously hidden shared genetic pathways that help to explain the links between type 2 diabetes and some cancers. More than five million people in the UK are now living with diabetes, of which 90% have type 2. With cancer now the biggest cause of death in people with diabetes in England, this knowledge could be critical in developing new and more personalised ways to predict, prevent and treat cancers in people with type 2 diabetes, potentially saving the lives of thousands.

This research also highlights the need for healthcare professionals and people living with type 2 diabetes to be vigilant for the symptoms of cancers, so problems can be detected and treated early.

The researchers further anticipate that their novel method will enable scientists to delve deeper into understanding how genetics influence the co-occurrence of other health conditions, opening new avenues for future research and advancements in tackling the growing concern of people developing multiple health conditions.

Professor Inga Prokopenko, Professor e-One Health and Head of Statistical Multi-Omics at the University of Surrey, said:

“We are witnessing the era of large population-based studies, where individual health is studied over decades, and health outcomes are followed. Combining such rich information from studies or national health records with genetic data enables new understanding into comorbid conditions. Such insight is extremely valuable for prevention of type 2 diabetes comorbidities and complications.”

First author, Dr Ayse Demirkan, Senior Lecturer in AI Multiomics for Health and Wellbeing at the University of Surrey, said: “It has long been speculated that there is a genetic link between Type 2 diabetes and certain cancers exist. However, the majority of the evidence were sourced from independent observations. We had the opportunity to for the first time investigate the relationships in a unique combined dataset enriched in cases of multiple cancers, thus we were able to evaluate the effect of each genetic variant for all five diseases simultaneously. 

“It does not mean that if you have Type 2 diabetes you will automatically develop cancer however it is importance to acknowledge the increased risk attributed to genetic and life-style factors to design personalised prevention strategies.”

Dr Elizabeth Robertson, Director of Research at Diabetes UK, said:

“Type 2 diabetes and cancers are complex conditions with a multitude of factors increasing people’s likelihood of developing them. This research sheds new light on the role that genetically determined factors play in why some people with type 2 diabetes are also at risk of breast, colorectal, and pancreatic cancer. 

“In time, this could help doctors to identify people earlier who are at risk of both type 2 diabetes and certain cancers, while paving the way to better, more personalised ways to prevent and treat the conditions.

“It’s important to remember that people who have genes that are linked to type 2 diabetes and cancers can still take steps to reduce their risk of both conditions, by getting support to manage your weight, eating well, keeping active and not smoking.” 

Dr Helen Croker, Assistant Director of Research and Policy at the World Cancer Research Fund, said:

“WCRF is proud to fund this important research which looks at a population of people that is particularly vulnerable to cancer. As cancer is now the leading cause of death among people with diabetes, understanding the complex genetic interplay between Type 2 diabetes and several cancer types is crucial for driving prevention strategies for this group of people.”

Notes for editor

• Study was co-funded by Diabetes UK, World Cancer Research Fund UK and International, European Commission H2020 and LongITools.
• Professor Inga Prokopenko and Dr Ayse Demirkan are available for interview on request
• For more information please email mediarelations@surrey.ac.uk