Diet-Dependent Metabolic Regulation of DNA Double-Strand Break Repair in Cancer: More Choices on the Menu

Despite several epidemiologic and preclinical studies supporting the role of diet in cancer progression, the complexity of the diet-cancer link makes it challenging to deconvolute the underlying mechanisms, which remain scantly elucidated. This review focuses on genomic instability as one of the cancer hallmarks affected by diet-dependent metabolic alterations. We discuss how altered dietary intake of meta-bolites of the one-carbon metabolism, including methionine, folate, and vitamins B and C, can impact the methylation processes and thereby tumorigenesis. We present the concept that the protumorigenic effect of certain diets, such as the Western diet, is in part due to a diet-induced erosion of the DNA repair capacity caused by altered epigenetic and epitranscriptomic landscapes, while the protective effect of other dietary patterns, such as the Mediterranean diet, can be partly explained by their ability to sustain a proficient DNA repair. In particular, considering that diet-dependent alterations of the one-carbon metabolism can impact the rate of methylation processes, changes in dietary patterns can affect the activity of writers and erasers of histone and RNA methyl marks and consequently impair their role in ensuring a proficient DNA damage repair.

Automated summary

This review explores the impact of diet on genomic instability and highlights the role of altered one-carbon metabolism metabolites in influencing methylation processes and tumorigenesis. It suggests that certain diets, like the Western diet, can erode DNA repair capacity due to changes in epigenetic and epitranscriptomic landscapes, while others, like the Mediterranean diet, may support proficient DNA repair. Changes in dietary patterns can affect the activity of writers and erasers of histone and RNA methyl marks, impairing their role in DNA damage repair.