DNA repair deficiency as key player in the development of obesity and the subsequent kidney cancer risk
Background: The number of obese people is steeply increasing and this surge is mirrored by a notable rise in kidney cancer. In 2012, researchers estimated that in Western Europe 22-29% of kidney cancers are attributable to obesity. The increase in obese individuals cannot be explained solely by high consumption of fat/sugar-rich diets and reduced physical activity. It does not explain why we all have that friend who eats a lot, yet never gains weight, or why another active person with a lower intake of fat and sugar puts on weight. Research indicates that weight gain is influenced by various interactions between our genes and our environment. Some people carry genes that vary slightly from the genes in the general population, but these variations can lead to non-functional proteins. Research in mice has shown that such variations in DNA repair genes can impair their DNA repair and make them more vulnerable to gain weight and develop diseases such as obesity and type-2 diabetes. DNA repair systems maintain DNA stability and prevent mutations that initiate cancer. Previous research shows that variations in DNA repair genes as well as being overweight or obese can increase the risk of kidney cancer. So far, the research community has hardly focused on the role of DNA repair in the development of obesity and kidney cancer risk.
Research plan: The researchers expect that genetic variations in DNA repair genes can load the gun, but exposure to obesogenic environmental stressors (increased caloric intake, low physical activity) will pull the trigger of a vicious circle, leading to obesity. The aim of this three year project is twofold: primarily to study if variations in DNA repair genes increase the risk to become obese, and secondly to asses if the harmful effects of such variations in DNA repair genes in overweight/obese individuals will make them more susceptible to develop kidney cancer. Using data collected by the UK Biobank, researchers will identify variations in DNA repair genes that are linked to higher weight gain, obesity and the occurrence of kidney cancer.
Potential Impact: This research will give crucial new insights in the role of DNA repair in the development of obesity and the risk of kidney cancer. Findings will help predict an individual's risk of obesity based on variations in their DNA repair genes, and will have a big impact for future prevention of obesity-linked kidney cancer.