Branched-chain amino acids (BCAAs), isoleucine, leucine and valine, are essential amino acids with vital roles in protein synthesis and energy production. We reviewed the fundamentals of BCAA metabolism in advanced cancer patients. BCAAs and various catabolic products act as signalling molecules, which activate mechanisms ranging from protein synthesis to insulin secretion. Recently, BCAA metabolism has been suggested to contribute to cancer progression. Of particular interest is the modulation of the mTOR activity by BCAAs. There are likely multiple pathways involved in BCAA metabolism implicated in carcinogenesis. Understanding the mechanism(s) underlying altered BCAAs metabolism will significantly advance the current understanding of nutrient involvement in carcinogenesis and direct future studies to unravel the significance of BCCA metabolites in tumor development and progression.

BACKGROUND/OBJECTIVES: Habitual coffee consumption was inversely associated with type 2 diabetes (T2D) and hyperglycemia in observational studies, but the causality of the association remains uncertain. This study tested a causal association of genetically predicted coffee consumption with T2D using the Mendelian randomization (MR) method. SUBJECTS/METHODS: We used five single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) associated with habitual coffee consumption in a previous genome-wide association study among Koreans. We analyzed the associations between IVs and T2D, fasting blood glucose (FBG), 2h-postprandial glucose (2h-PG), and glycated haemoglobin (HbA1C) levels. The MR results were further evaluated by standard sensitivity tests for possible pleiotropism. RESULTS: MR analysis revealed that increased genetically predicted coffee consumption was associated with a reduced prevalence of T2D; ORs per one-unit increment of logtransformed cup per day of coffee consumption ranged from 0.75 (0.62–0.90) for the weighted mode-based method to 0.79 (0.62–0.99) for Wald ratio estimator. We also used the inverse-variance-weighted method, weighted median-based method, MR-Egger method, and MR-PRESSO method. Similarly, genetically predicted coffee consumption was inversely associated with FBG and 2h-PG levels but not with HbA1c. Sensitivity measures gave similar results without evidence of pleiotropy. CONCLUSIONS A genetic predisposition to habitual coffee consumption was inversely associated with T2D prevalence and lower levels of FBG and 2h-PG profiles. Our study warrants further exploration.