We report that Cdkn2a deficiency protects mice against high fat diet-induced obesity, increases energy expenditure and modulates adaptive thermogenesis, in addition to improving insulin sensitivity.
These results show that obesity activates breast stromal adipocytes through p16 downregulation, which upregulates leptin and promotes procarcinogenic processes.
Among the candidate genes studied, the CDKN2A-rs10811661 polymorphism was found to be the most significant factor associated with prediabetes in the model unadjusted and adjusted for age, sex, obesity-related traits, systolic blood pressure, dyslipidemia, socio-economic status, and lifestyle factors.
This study provides evidence that obesity and occupational exposure increase the risk of developing esophageal cancer through an enhancement of CDKN2A/p16 promoter methylation.