Serum Trimethylamine N-oxide, Carnitine, Choline, and Betaine in Relation to Colorectal Cancer Risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study.
Serum Trimethylamine N-oxide, Carnitine, Choline, and Betaine in Relation to Colorectal Cancer Risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study.
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DOI：
10.1158/1055-9965.epi-16-0948
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发表时间：
2017-06
期刊：
影响因子：
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通讯作者：
Sinha R
中科院分区：
文献类型：
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作者：
Guertin KA;Li XS;Graubard BI;Albanes D;Weinstein SJ;Goedert JJ;Wang Z;Hazen SL;Sinha R
TMAO 是一种由肠道微生物群产生的胆碱衍生代谢物，其生物标志物前体与结直肠癌风险的关系尚未得到充分评估。我们在α-生育酚、β-胡萝卜素癌症预防 (ATBC) 研究中对男性吸烟者进行了一项巢式病例对照研究，研究了 TMAO 及其生物标志物前体（胆碱、肉碱和甜菜碱）的血清浓度与结直肠癌发生风险之间的关系。我们使用 LC-MS/MS 测量了 644 例结直肠癌病例和 644 例对照的基线空腹血清样本中的生物标志物浓度。 Logistic 回归模型通过血清 TMAO、胆碱、肉碱和甜菜碱浓度的四分位数 (Q) 估计结直肠癌的比值比 (OR) 和 95% 置信区间 (CI)。 ATBC 基线时血清胆碱较高的男性在随后的 14 ± 10 年内（中位数 ± IQR）患结直肠癌的风险大约高出 3 倍（在完全调整的模型中，Q4 与 Q1 OR，3.22；95% CI，2.24–4.61；P 趋势<0.0001）。血清胆碱对于预测结直肠癌发生发展的预后价值对于近端结肠癌、远端结肠癌和直肠结肠癌同样有效（所有 P<0.0001）。血清TMAO、肉毒碱或甜菜碱与结直肠癌风险之间的相关性不具有统计学意义（分别为P=0.25、P=0.71和P=0.61）。较高的血清胆碱浓度（但不是TMAO、肉碱或甜菜碱）与结直肠癌风险增加相关。血清胆碱水平对于预测所有解剖亚部位的结直肠癌发生风险具有很强的预后价值，表明胆碱代谢改变在结直肠癌发病机制中的作用。
TMAO, a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk. We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We measured biomarker concentrations in baseline fasting serum samples from 644 incident colorectal cancer cases and 644 controls using LC-MS/MS. Logistic regression models estimated the odds ratio (OR) and 95% confidence interval (CI) for colorectal cancer by quartile (Q) of serum TMAO, choline, carnitine and betaine concentrations. Men with higher serum choline at ATBC baseline had approximately 3-fold greater risk of developing colorectal cancer over the ensuing (median ± IQR) 14 ±10 years (in fully adjusted models, Q4 vs. Q1 OR, 3.22; 95% CI, 2.24–4.61; P trend<0.0001). The prognostic value of serum choline for prediction of incident colorectal cancer development was similarly robust for proximal, distal and rectal colon cancers (all P<0.0001). The association between serum TMAO, carnitine, or betaine and colorectal cancer risk was not statistically significant (P=0.25, P=0.71 and P=0.61, respectively). Higher serum choline concentration (but not TMAO, carnitine, or betaine) was associated with increased risk of colorectal cancer. Serum choline levels showed strong prognostic value for prediction of incident colorectal cancer risks across all anatomical subsites, suggesting a role of altered choline metabolism in colorectal cancer pathogenesis.