期刊
CANCER PREVENTION RESEARCH
卷 2, 期 12, 页码 1023-1030出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1940-6207.CAPR-09-0234
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资金
- NCI/NIH [PO1 CA4108, P01-CA-41108]
- National Cancer Institute [1K07CA10629-01A1]
- NATIONAL CANCER INSTITUTE [P01CA041108] Funding Source: NIH RePORTER
Purpose: Ursodeoxycholic acid (UDCA) was one of the earliest agents investigated as a drug for colorectal cancer prevention. However, UDCA failed to show efficacy to prevent the development of colorectal adenomas in a large, phase III, randomized, placebo-controlled trial. We re-evaluated the effect of UDCA in men and women separately, based on sex-specific differences in bile acid metabolism and suspected variation in etiologic factors contributing to colorectal cancer risk. Experimental Design: We conducted a secondary analysis of the efficacy of UDCA to prevent colorectal adenoma in men (n = 804) and women (n = 388). Results: We found no reduction in risk of any metachronous adenoma with UDCA treatment in men or women. However, UDCA treatment significantly lowered the odds of advanced lesions [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.43-0.89] in men, but not women. We also observed significantly higher odds of advanced lesions with UDCA treatment in women who were younger (age, <65 years; OR, 3.24; 95% CI, 1.10-9.56), obese (body mass index, >= 30 kg/m(2); OR, 5.45; 95% CI, 1.42-20.9), or in the highest tertile of total dietary fat (>= 56.2 g/day; OR, 3.48; 95% CI, 1.35-8.95). In a multivariate model, the interactive effect of fat intake accounted for the modulating effects of age and body mass index in women. Conclusion: Our findings support the use of UDCA for preventing advanced colorectal adenomas in men. The increased odds of adenoma among women with high fat intake suggest a previously unrecognized harm that warrants further study, especially given the chronic exposure to UDCA in patients with primary biliary cirrhosis and the increasing investigational use of UDCA for several other conditions.
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