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Inflammation-Associated Serum and Colon Markers as Indicators of Dietary Attenuation of Colon Carcinogenesis in ob/ob Mice

Authors' Affiliations: ¹ Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland; ² Center for Cancer Research, ³ Cancer Prevention Fellowship Program, Office of Preventive Oncology, and ⁴ Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland; and ⁵ Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan

Requests for reprints: Roycelynn Mentor-Marcel, National Cancer Institute-Frederick, 1050 Boyles Street, Building 576, Room 110, Frederick, MD 21702. Phone: 301-846-1651; Fax: 301-846-6907; E-mail: marcelr{at}mail.nih.gov.

Although inflammatory cytokines and obesity-associated serum proteins have been reported as biomarkers of colorectal adenoma risk in humans, little is known of biomarkers of response to interventions that attenuate tumorigenesis. Dietary navy beans and their fractions attenuate colon carcinogenesis in carcinogen-induced genetically obese mice. We hypothesized that this attenuation would be associated with changes in inflammatory cytokines and obesity-related serum proteins that may serve as measures of efficacy. ob/ob mice (n = 160) were injected with the carcinogen azoxymethane (AOM) to induce colon cancer and randomly placed on one of four diets (control, whole navy bean, bean residue fraction, or bean extract fraction) for 26 to 28 wk. Serum was analyzed for 14 inflammation- or obesity-related proteins, and colon RNA was analyzed for expression of 84 inflammation-associated genes. Six of 14 serum proteins were increased [i.e., interleukin (IL)-4, IL-5, IL-6, IL-10, IFN, granulocyte macrophage colony-stimulating factor] in hyperplastic/dysplastic stages of colon carcinogenesis. Bean-fed mice had significantly higher monocyte chemoattractant protein-1 and lower IL-6 levels in serum. In colon mucosa, 55 of 84 inflammation-associated genes differed between AOM-induced and noninduced mice. Of the 55 AOM-induced genes, 5 were counteracted by bean diets, including IL-6 whose increase in expression levels was attenuated by bean diets in AOM-induced mice. In summary, IL-6 emerged as a serum protein that was increased in hyperplastic/dysplastic stages of colon carcinogenesis, but attenuated with bean-based diet in serum and colon mucosa. Changes in a subset of inflammation-associated serum proteins and colon gene expression may serve as response indicators of dietary attenuation of colon carcinogenesis.

Key Words: nutrition • colon • inflammation • obesity • biomarkers

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