循环氨基酸水平与欧洲癌症与营养观察和英国生物银行队列中的结直肠癌风险相关。
Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts.
发表日期：2023 Feb 28
作者：
Joseph A Rothwell, Jelena Bešević, Niki Dimou, Marie Breeur, Neil Murphy, Mazda Jenab, Roland Wedekind, Vivian Viallon, Pietro Ferrari, David Achaintre, Audrey Gicquiau, Sabina Rinaldi, Augustin Scalbert, Inge Huybrechts, Cornelia Prehn, Jerzy Adamski, Amanda J Cross, Hector Keun, Marc Chadeau-Hyam, Marie-Christine Boutron-Ruault, Kim Overvad, Christina C Dahm, Therese Haugdahl Nøst, Torkjel M Sandanger, Guri Skeie, Raul Zamora-Ros, Kostas K Tsilidis, Fabian Eichelmann, Matthias B Schulze, Bethany van Guelpen, Linda Vidman, Maria-José Sánchez, Pilar Amiano, Eva Ardanaz, Karl Smith-Byrne, Ruth Travis, Verena Katzke, Rudolf Kaaks, Jeroen W G Derksen, Sandra Colorado-Yohar, Rosario Tumino, Bas Bueno-de-Mesquita, Paolo Vineis, Domenico Palli, Fabrizio Pasanisi, Anne Kirstine Eriksen, Anne Tjønneland, Gianluca Severi, Marc J Gunter
来源：
BMC Medicine
摘要：
氨基酸代谢在结直肠癌患者中受到失调；然而，目前还不清楚患者诊断前的氨基酸水平是否与随后的结直肠癌风险相关。我们在欧洲癌症和营养前瞻性研究（EPIC）和英国生物库（UK Biobank）队列中研究了循环氨基酸水平与结直肠癌风险的关系。在EPIC中，对于在基线时进行了快速血浆或血清样本测试的654例新发结直肠癌患者和654例匹配对照组测定了13-21种氨基酸的浓度。然后，在UK Biobank中对结直肠癌风险相关的氨基酸进行了虚警率（FDR）调整，并检测了其中9种氨基酸在111,323名参与者中的关联性，其中1,221例为新发结直肠癌患者。
在EPIC中，组氨酸水平与结直肠癌风险呈负相关（每标准差[SD]下降0.80的几率比[OR]，95％置信区间[CI]为0.69-0.92，FDR P值为0.03），并在UK Biobank中得到了验证（每SD下降0.93的风险比[HR]，95％CI为0.87-0.99，P值为0.03）。在EPIC中，谷氨酰胺水平与结直肠癌风险呈边缘负相关（每SD下降0.85的OR，95％CI为0.75-0.97，FDR P值为0.08），在UK Biobank中也呈相似的趋势（HR 0.95，95％CI为0.89-1.01，P=0.09）。在两个队列中，当排除了跟踪2或5年内诊断的病例时，相关性变化极小。
更高的循环组氨酸水平与较低的结直肠癌风险在两个大型前瞻性队列中呈正相关。值得进一步研究组氨酸代谢的作用以及谷氨酰胺在结直肠癌发展中的潜在作用。©2023年，作者。
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.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.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.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.© 2023. The Author(s).