Bae Sajin, Ulrich Cornelia M, Neuhouser Marian L, Malysheva Olga, Bailey Lynn B, Xiao Liren, Brown Elissa C, Cushing-Haugen Kara L, Zheng Yingye, Cheng Ting-Yuan David, Miller Joshua W, Green Ralph, Lane Dorothy S, Beresford Shirley A A, Caudill Marie A
Division of Nutritional Sciences, Cornell University, Ithaca, New York.
Fred Hutchinson Cancer Research Center, Seattle, Washington. German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany. Huntsman Cancer Institute, Salt Lake City, Utah.
Cancer Res. 2014 Dec 15;74(24):7442-52. doi: 10.1158/0008-5472.CAN-14-1835. Epub 2014 Oct 21.
Few studies have examined associations between plasma choline metabolites and risk of colorectal cancer. Therefore, we investigated associations between plasma biomarkers of choline metabolism [choline, betaine, dimethylglycine, and trimethylamine N-oxide (TMAO)] and colorectal cancer 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). Colorectal cancer was assessed by self-report and confirmed by medical records over the mean of 5.2 years of follow-up. Baseline plasma choline metabolites were measured by LC/MS-MS. In multivariable-adjusted conditional logistic regression models, plasma choline tended to be positively associated with rectal cancer risk [OR (95% confidence interval, CI)(highest vs. lowest quartile) = 2.44 (0.93-6.40); P trend = 0.08], whereas plasma betaine was inversely associated with colorectal cancer 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 colorectal cancer 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 colorectal cancer 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 colorectal cancer. The positive association between plasma TMAO and colorectal cancer risk is consistent with an involvement of the gut microbiome in colorectal cancer pathogenesis.
很少有研究探讨血浆胆碱代谢物与结直肠癌风险之间的关联。因此，在女性健康倡议观察性研究中的一项病例对照研究中，我们调查了绝经后女性中胆碱代谢的血浆生物标志物[胆碱、甜菜碱、二甲基甘氨酸和氧化三甲胺（TMAO）]与结直肠癌风险之间的关联。我们选择了835对匹配的病例对照，病例进一步按肿瘤部位（近端、远端或直肠）和分期（局部/区域或转移）分层。通过自我报告评估结直肠癌，并在平均5.2年的随访期间通过病历进行确认。通过液相色谱/质谱联用仪测量基线血浆胆碱代谢物。在多变量调整的条件逻辑回归模型中，血浆胆碱倾向于与直肠癌风险呈正相关[比值比（95%置信区间，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呈负相关[0.68（0.47 - 0.99）；P趋势=0.01]，与局部/区域肿瘤呈负相关[0.64（0.42 - 0.99）；P趋势=0.009]。值得注意的是，血浆甜菜碱:胆碱比值与总体结直肠癌呈负相关[0.56（0.39 - 0.82）；P趋势=0.004]，与近端[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[0.50（0.33 - 0.76）；P趋势=0.001]肿瘤也呈负相关。最后，血浆TMAO是肠道细菌产生的胆碱氧化衍生物，与直肠癌呈正相关[3.38（1.25 - 9.16）；P趋势=0.02]，并且在血浆维生素B12水平较低（与较高相比）的女性中与总体结直肠癌风险呈正相关（P交互作用=0.003）。总体而言，这些数据表明胆碱代谢的改变可能在疾病发展早期出现，可能与结直肠癌风险较高有关。血浆TMAO与结直肠癌风险之间的正相关与肠道微生物群参与结直肠癌发病机制一致。
