Alteration of gene expression in macroscopically normal colonic mucosa from individuals with a family history of sporadic colon cancer.
OBJECTIVE
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-gamma, 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.
Hao
Chun-Yi
CY
California Pacific Medical Center Research Institute, 475 Brannen Street, San Francisco, CA 94107, USA.
Moore
Dan H
DH
Wong
Patrick
P
Bennington
James L
JL
Lee
Nancy M
NM
Chen
Ling-Chun
LC
D000293:Adolescent; D000328:Adult; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics*; D051546:Cyclooxygenase 2; D005192:Family Health; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D047494:PPAR delta / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000235:genetics
D016209:Interleukin-8; D008565:Membrane Proteins; D047494:PPAR delta; D047495:PPAR gamma; D000685:Serum Amyloid A Protein; D012313:RNA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases