Plasma Choline Metabolites and Colorectal Cancer Risk in the Women's Health Initiative Observational Study

被引:202
作者
Bae, Sajin [1 ]
Ulrich, Cornelia M. [2 ,3 ,4 ,5 ]
Neuhouser, Marian L. [2 ]
Malysheva, Olga [1 ]
Bailey, Lynn B. [6 ]
Xiao, Liren [2 ]
Brown, Elissa C. [2 ]
Cushing-Haugen, Kara L. [2 ]
Zheng, Yingye [2 ]
Cheng, Ting-Yuan David [2 ]
Miller, Joshua W. [7 ,8 ]
Green, Ralph [8 ]
Lane, Dorothy S. [9 ]
Beresford, Shirley A. A. [2 ]
Caudill, Marie A. [1 ]
机构
[1] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA
[2] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA
[3] German Canc Res Ctr, Heidelberg, Germany
[4] Natl Ctr Tumor Dis, Heidelberg, Germany
[5] Huntsman Canc Inst, Salt Lake City, UT USA
[6] Univ Georgia, Dept Food & Nutr, Athens, GA 30602 USA
[7] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA
[8] Univ Calif Davis, Dept Med Pathol & Lab Med, Davis, CA 95616 USA
[9] SUNY Stony Brook, Sch Med, Dept Prevent Med, Stony Brook, NY 11794 USA
基金
美国国家卫生研究院;
关键词
DNA METHYLATION; GUT MICROBIOTA; MALIGNANT-TRANSFORMATION; PHOSPHOLIPID-METABOLISM; POSTMENOPAUSAL WOMEN; FOLATE STATUS; COLON-CANCER; BIOMARKERS; ATHEROSCLEROSIS; NUTRIENT;
D O I
10.1158/0008-5472.CAN-14-1835
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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/MSMS. 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. (C)2014 AACR.
引用
收藏
页码:7442 / 7452
页数:11
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