日本人群研究发现高支链氨基酸可降低男性结直肠癌前病变风险
结直肠癌位居全球恶性肿瘤发病率第三位，死亡率第四位。在肿瘤防治形势严峻的当下，结直肠癌在一定程度上属于可以预防的疾病。既往有研究分析了结直肠癌、结直肠腺瘤（结直肠癌前病变）风险与饮食的相关性，包括肉类、鱼、谷类、水果、蔬菜的摄入，这些食物包括众多可能影响癌症发生的生物活性成分，涉及众多信号通路，同时也是日常支链氨基酸的重要来源，而支链氨基酸在肿瘤形成过程中的作用还有待深入探索。支链氨基酸属于必需氨基酸，包括亮氨酸、异亮氨酸、缬氨酸，约占日常蛋白质总摄入的15%～25%。与其他氨基酸不同，支链氨基酸主要在骨骼肌内进行代谢，而骨骼肌是影响血糖的重要器官。有回顾研究显示，饮食高支链氨基酸摄入量与糖尿病风险成反比。肥胖及其相关代谢并发症，包括胰岛素抵抗、糖尿病均被认为是结直肠癌的风险因素。动物研究证据表明支链氨基酸可能预防结直肠癌发生，然而尚无研究评估支链氨基酸对人类结直肠癌发生的可能影响。支链氨基酸可能在抑制结直肠癌发生中起到一定作用，而支链氨基酸对结直肠腺瘤的影响还是未知数。
2016年12月22日，欧洲肿瘤内科学会和日本肿瘤内科学会官方期刊、牛津大学出版社旗下《肿瘤学年鉴》在线发表日本东京国家癌症中心、日本川崎味之素有限公司创新研究所的研究报告，以日本中老年人群为研究对象，分析了血浆支链氨基酸（亮氨酸、异亮氨酸、缬氨酸）浓度与结直肠腺瘤风险是否有相关性。
该研究向2004～2005年在癌症筛查时经全结肠镜检查确诊结直肠腺瘤的629例患者和584例对照者发放自我管理饮食和生活方式调查问卷，并检测亮氨酸、异亮氨酸、缬氨酸的血浆浓度，校正其他可能影响因素后，使用无条件逻辑回归模型分析支链氨基酸与结直肠腺瘤风险之间相关性的比值比和95%置信区间。
结果发现，校正其他可能影响因素后，亮氨酸、缬氨酸、全部支链氨基酸的血浆浓度越高，结直肠腺瘤的风险越低，其中亮氨酸有统计学意义。亮氨酸、缬氨酸、全部支链氨基酸的血浆浓度最高与最低四分位数相比，结直肠腺瘤的风险分别降低40%、32%、32%（多变量校正比值比分别为：0.60、0.68、0.68，95%置信区间分别为：0.42～0.87、0.48～0.97、0.69～0.98，趋势P值分别为：0.006、0.09、0.10）。
根据性别进一步分析显示，这种反比关系在男性中有统计学意义，在女性中无统计学意义。亮氨酸、缬氨酸、全部支链氨基酸的血浆浓度最高与最低四分位数相比，男性结直肠腺瘤的风险分别降低50%、40%、42%（多变量校正比值比分别为：0.50、0.60、0.58，95%置信区间分别为：0.32～0.80、0.38～0.95、0.37～0.93，趋势P值分别为：0.003、0.01、0.04），女性结直肠腺瘤的风险分别降低22%、23%、16%（多变量校正比值比分别为：0.78、0.77、0.84，95%置信区间分别为：0.42～1.45、0.41～1.43、0.45～1.57，趋势P值分别为：0.44、0.85、0.81）。
因此，该研究结果表明，支链氨基酸（特别是亮氨酸）可能对预防结直肠癌发生有积极影响，至少在癌前早期阶段，尤其对于男性。支链氨基酸与结直肠癌发生之间潜在相关性的机理值得进一步研究。
Ann Oncol. 2016 Dec 22. [Epub ahead of print]
Association of plasma concentrations of branched-chain amino acids with risk of colorectal adenoma in a large Japanese population.
Budhathoki S, Iwasaki M, Yamaji T, Yamamoto H, Kato Y, Tsugane S.
National Cancer Center, Tokyo, Japan; Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
BACKGROUND: Available evidence from animal studies suggests that branched-chain amino acids (BCAAs) may have a protective effect against colorectal carcinogenesis. However, a possible effect of BCAAs against colorectal neoplasia has not been evaluated in humans. Here, we aimed to evaluate whether plasma concentrations of BCAA are associated with the risk of colorectal adenoma (CRA), a precursor lesion of colorectal cancer.
PATIENTS AND METHODS: Colorectal adenoma cases and controls were identified from examinees who underwent total colonoscopy as part of a cancer screening program between 2004 and 2005 and responded to self-administered dietary and lifestyle questionnaires. We measured plasma concentrations of leucine, isoleucine and valine in 629 patients with adenoma and 584 controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for the association between BCAA and CRA risk after adjustment for potential confounders.
RESULTS: High plasma concentrations of leucine, valine and total BCAA were inversely associated with CRA risk after adjustment of potential confounders. The multivariate-adjusted ORs for the highest versus lowest quartiles were 0.60 (95% CI 0.42-0.87, Ptrend=0.006) for leucine, 0.68 (95% CI 0.48-0.97, Ptrend=0.09) for valine and 0.68 (95% CI 0.48-0.98, Ptrend=0.10) for total BCAA. Further analysis by gender revealed that this inverse association was clearly evident in men, but not in women: the corresponding OR for leucine, valine and total BCAA was 0.50 (95% CI 0.32-0.80, Ptrend=0.003), 0.60 (95% CI 0.38-0.95, Ptrend=0.01) and 0.58 (95% CI 0.37-0.93, Ptrend=0.04), respectively, in men and 0.78 (95% CI 0.42-1.45, Ptrend=0.44), 0.77 (95% CI 0.41-1.43, Ptrend=0.85) and 0.84 (95% CI 0.45-1.57, Ptrend=0.81), respectively, in women.
CONCLUSION: Our finding suggests that BCAAs may have a beneficial influence against the process of colorectal carcinogenesis, at least in the early stage. The mechanisms underlying this potential association between BCAA and colorectal carcinogenesis warrant further investigation.
KEYWORDS: Branched-chain amino acid; case-control study.; colorectal adenoma; epidemiology; isoleucine; leucine; valine
KEY MESSAGE: The role of branched-chain amino acids (BCAAs) in the pathogenesis of colorectal neoplasia is not clear. In this study with more than 1200 adenoma cases and controls, we observed that a higher circulating concentration of BCAA was inversely associated with the risk of colorectal adenoma. This finding provides additional evidence that BCAA has a protective role in colorectal carcinogenesis.
PMID: 28011449
PII: mdw680
DOI: 10.1093/annonc/mdw680
