Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts

Abstract

Background Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts. Methods Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases. Results Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69–0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87–0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75–0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89–1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded. Conclusions Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.

Long-Term Tracking of the Effects of Colostrum-Derived Lacticaseibacillus rhamnosus Probio-M9 on Gut Microbiota in Mice with Colitis-Associated Tumorigenesis

“…Some amino acids play an important role in tumorigenesis. Dietary methionine supplementation activates T cells and suppresses tumor progression in immunocompetent mice [ 20 ]; the serum level of lysine is inversely associated with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts [ 21 ]. The recovery of the amino acid pathways affected by AOM/DSS may also be a potential strategy for the treatment of CAC.…”

Plasma metabolomic differences in early-onset compared to average-onset colorectal cancer

“…Recent research has demonstrated the ability of metabolomics to identify metabolic pathway alterations associated with CRC 11 , 29 – 37 . These include TCA cycle-related metabolites reflecting impaired mitochondrial respiration and oxidative stress 10 , 11 , 32 .…”

Circulating metabolome landscape in Lynch Syndrome

“…Compelling evidence suggests that some circulating metabolites are causally related to cancer development. Lipids and amino acids were the most abundant circulating metabolites associated with CRC risk 5,[8][9][10] . Elevated levels of triglycerides, phospholipids, and cholesterol may promote cancer cell growth and proliferation by serving as an energy source and inhibiting CD8 + T cell proliferation 11 .…”

“…Amino acids function as building blocks of proteins, precursors of various signaling molecules, and energy sources. Levels of certain amino acids, such as Alanine and Histidine, have been shown to inversely associate with the cancer stage 12 . In addition, Histidine concentration in blood was shown to be inversely associated with CRC risk 12 .…”

“…Levels of certain amino acids, such as Alanine and Histidine, have been shown to inversely associate with the cancer stage 12 . In addition, Histidine concentration in blood was shown to be inversely associated with CRC risk 12 . Furthermore, circulating amino acid levels can in uence immune cell activity, potentially impacting cancer development, as amino acids are vital for the basal metabolism of immune cells, and activated immune cells require more amino acids 13 .…”