Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study.
Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study.
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DOI：
10.1158/0008-5472.can-14-1835
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发表时间：
2014-12-15
期刊：
影响因子：
11.2
通讯作者：
Caudill MA
中科院分区：
文献类型：
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作者：
Bae S;Ulrich CM;Neuhouser ML;Malysheva O;Bailey LB;Xiao L;Brown EC;Cushing-Haugen KL;Zheng Y;Cheng TY;Miller JW;Green R;Lane DS;Beresford SA;Caudill MA
很少有研究考察血浆胆碱代谢产物与结直肠癌(CRC)风险之间的关系。因此，我们在一项嵌套在妇女健康倡议观察性研究中的病例对照研究中，调查了绝经后妇女血浆胆碱代谢生物标志物[胆碱、甜菜碱、二甲基甘氨酸和三甲胺氮氧化物(TMAO)]与结直肠癌风险的关系。我们选择了835对匹配的病例对照，并根据肿瘤部位(近端、远端或直肠)和分期(局部/区域或转移)对病例进行了进一步分层。CRC通过自我报告进行评估，并由医疗记录证实，平均随访时间为5.2年。用液相色谱-串联质谱法测定基础血浆胆碱代谢产物。在多变量调整的条件Logistic回归模型中，血浆胆碱与直肠癌风险呈正相关[OR(95%CI)最高四分位数与最低四分位数=2.44(0.93~6.40)；P趋势=0.08]，而血浆甜菜碱与总体结直肠癌[0.68(0.47~0.99)；P趋势=0.01]及局部/区域肿瘤[0.64(0.42~0.99)；P趋势=0.009]呈负相关。值得注意的是，血浆甜菜碱/胆碱比值与整体结直肠癌[0.56(0.39-0.82)；P-趋势=0.004]以及近端[0.66(0.41-1.06)；P-趋势=0.049]、直肠[0.27(0.10-0.78)；P-趋势=0.02]和局部/区域[0.5(0.33-0.76)；P-趋势=0.001]肿瘤呈负相关。最后，在血浆维生素B12水平较低(与较高)的女性中，血浆TMAO，一种由肠道细菌产生的胆碱的氧化衍生物，与直肠癌呈正相关[3.38(1.25-9.16)；P-趋势=0.02]，与总体结直肠癌风险呈正相关(P-交互作用=0.003)。总而言之，这些数据表明，胆碱代谢的改变可能出现在疾病发展的早期，可能与结直肠癌的高风险相关。血浆TMAO与CRC风险之间的正相关与肠道微生物群参与CRC的发病机制是一致的。
Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer (CRC). Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine and trimethylamine N-oxide (TMAO)] and CRC risk among postmenopausal women in a case-control study nested within the Women’s Health Initiative Observational Study. We selected 835 matched case-control pairs, and cases were further stratified by tumor site (proximal, distal, or rectal) and stage (local/regional or metastatic). CRC was assessed by self-report and confirmed by medical records over the mean 5.2y of follow-up. Baseline plasma choline metabolites were measured by liquid chromatography-tandem mass spectrometry. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% CI)highest vs. lowest quartile=2.44 (0.93–6.40);P-trend=0.08], while plasma betaine was inversely associated with CRC overall [0.68 (0.47–0.99);P-trend=0.01] and with local/regional tumors [0.64 (0.42–0.99);P-trend=0.009]. Notably, the plasma betaine:choline ratio was inversely associated with CRC overall [0.56 (0.39–0.82);P-trend=0.004] as well as with proximal [0.66 (0.41–1.06);P-trend=0.049], rectal [0.27 (0.10–0.78);P-trend=0.02] and local/regional [0.50 (0.33–0.76);P-trend=0.001] tumors. Finally, plasma TMAO, an oxidative derivative of choline produced by intestinal bacteria, was positively associated with rectal cancer [3.38 (1.25–9.16);P-trend=0.02] and with overall CRC risk among women with lower (vs. higher) plasma vitamin B12 levels (P-interaction=0.003). Collectively, these data suggest that alterations in choline metabolism, which may arise early in disease development, may be associated with higher risk of CRC. The positive association between plasma TMAO and CRC risk is consistent with an involvement of the gut microbiome in CRC pathogenesis.