循环氨基酸水平与欧洲癌症与营养前瞻性调查和英国生物库队列中的结直肠癌风险。
Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts.
机构信息
Centre for Epidemiology and Population Health (Inserm U1018), Exposome and Heredity team, Faculté de Médecine, Université Paris-Saclay, UVSQ, Gustave Roussy, F-94805, Villejuif, France.
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
出版信息
BMC Med. 2023 Feb 28;21(1):80. doi: 10.1186/s12916-023-02739-4.
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.
背景
氨基酸代谢在结直肠癌患者中失调；然而，尚不清楚诊断前的氨基酸水平是否与结直肠癌的后续风险相关。我们在欧洲癌症前瞻性调查和英国生物库队列中研究了与结直肠癌风险相关的循环氨基酸水平。
方法
在 EPIC 中，在 654 例新发结直肠癌病例和 654 例匹配对照的基线空腹血浆或血清样本中测定了 13-21 种氨基酸的浓度。在用错误发现率（FDR）校正后，与结直肠癌风险相关的氨基酸在英国生物库中进行了测试，其中 111323 名参与者中有 9 种氨基酸的测量值，其中 1221 例为新发结直肠癌病例。
结果
组氨酸水平与 EPIC 中的结直肠癌风险呈负相关（每标准差的比值比[OR]为 0.80，95%置信区间[CI]为 0.69-0.92，FDR P 值=0.03）和英国生物库（每标准差的 HR 为 0.93，95%CI 为 0.87-0.99，P 值=0.03）。在 EPIC 中，谷氨酰胺水平与结直肠癌风险呈边缘负相关（OR 为 0.85 每标准差，95%CI 为 0.75-0.97，FDR P 值=0.08），在英国生物库中也呈相似趋势（HR 为 0.95，95%CI 为 0.89-1.01，P=0.09）。在这两个队列中，当排除随访 2 或 5 年内诊断的病例时，关联变化很小。
结论
在两个大型前瞻性队列中，较高的循环组氨酸水平与结直肠癌风险降低相关。需要进一步研究以确定组氨酸代谢的作用，以及潜在的谷氨酰胺在结直肠癌发展中的作用。
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