Plasma Choline Metabolites and Colorectal Cancer Risk in the Women's Health Initiative Observational Study
| Autor: | Joshua W. Miller, Sajin Bae, Cornelia M. Ulrich, Shirley A.A. Beresford, Ralph Green, Dorothy S. Lane, Liren Xiao, Yingye Zheng, Tongguang Cheng, Marian L. Neuhouser, Marie A. Caudill, Olga V. Malysheva, Lynn B. Bailey, Elissa C. Brown, Kara L. Cushing-Haugen |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
medicine.medical_specialty Colorectal cancer Oncology and Carcinogenesis Disease Gastroenterology Article Choline Pathogenesis Dimethylglycine Methylamines chemistry.chemical_compound Betaine Clinical Research Risk Factors Internal medicine medicine Humans Oncology & Carcinogenesis Vitamin B12 Cancer Nutrition Aged business.industry Prevention Women's Health Initiative Middle Aged medicine.disease Colo-Rectal Cancer Endocrinology Oncology chemistry Women's Health Female Digestive Diseases Colorectal Neoplasms business |
| Zdroj: | Cancer research, vol 74, iss 24 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-14-1835 |
| Popis: | 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. Cancer Res; 74(24); 7442–52. ©2014 AACR. |
| Databáze: | OpenAIRE |
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