Obesity and cancer: Relevance of DNA damage response

• DNA damage response (DDR) molecules regulate many cellular processes, and their alterations are linked to various diseases. • Obesity-related factors increase DNA damage and impair DNA repair mechanisms. • This review highlights how obesity-driven DDR disruption promotes cancer cell proliferation. • Adipokines, oxidative stress, inflammation, gut microbiota, and metabolic changes strongly influence DDR in obesity. • Weight-loss interventions improve DDR function and reduce cancer risk. Obesity is a non-communicable, multifactorial disorder that has steadily emerged as one of the major global health concerns. It significantly increases the risk of diabetes, cardiovascular diseases and cancer. In obesity, the accumulation of excess fat causes increase in the circulatory levels of adipose tissue-specific hormones (adipokines) and exacerbates carbohydrate-fuelled metabolic stress. These factors promote oxidative and genotoxic stress, resulting in chronic inflammation. Moreover, obesity-related factors contribute to increase in DNA damage and disrupt the DNA Damage Response (DDR), thereby promoting genomic instability. Consequently, obesity may facilitate a complex, multi-step process of cellular transformation and cancer progression. However, the mechanisms linking obesity-associated DDR alterations to cancer progression are active areas of investigation. Therefore, elucidating these aspects of DDR in obesity could enhance our understanding of the risk assessment and facilitate advancement in treatment strategies for patients with cancers and obesity.