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Alteration of Gene Expression in Macroscopically Normal Colonic Mucosa from Individuals with a Family History of Sporadic Colon Cancer

California Pacific Medical Center Research Institute, San Francisco, California

Requests for reprints: Ling-Chun Chen, California Pacific Medical Center Research Institute, 475 Brannen Street, Suite 220, San Francisco, CA 94107. Phone: 415-600-1745; Fax: 415-600-1390; E-mail: chenlc{at}sutterhealth.org.

Purpose: We have shown that the expression of several genes associated with human colon cancer is altered in the morphologically normal colonic mucosa (MNCM) of APC^min mice and humans with colon cancers. To determine whether these alterations also occur in the MNCM of individuals who have not developed colon cancer but are at high risk of doing so, we measured gene expression in the MNCM of individuals with a family history of colon cancer.

Methods: Expression of 16 genes in the MNCM of 12 individuals with a first-degree relative with sporadic colon cancer and 16 normal controls were measured by quantitative reverse transcription-PCR. All subjects tested had normal colonoscopic examinations. Biopsy samples of MNCM were obtained from the ascending, transverse, descending, and rectosigmoid regions of the colon (2-8 biopsy samples were obtained from each region).

Results: Relative to normal controls, the expression of several genes, including PPAR-, SAA1, and IL-8 were significantly altered in the macroscopically normal rectosigmoid mucosa from individuals with a family history of colon cancer.

Conclusions: Molecular abnormalities that precede the appearance of adenomatous polyp are present in the MNCM of individuals who have a family history of colon cancer. This observation raises the possibility of screening for individuals who are at an increased risk of developing colon cancer by analysis of gene expression in rectosigmoid biopsy samples. To assess this possibility, prospective studies will be needed to determine whether or not altered gene expression is associated with the subsequent development of adenomatous polyps and/ or colonic carcinomas.

Key Words: colorectal cancer • premalignant lesions • Gastrointestinal cancers: colorectal

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