Increased colorectal epithelial cell proliferation and crypt fission associated with obesity and roux-en-Y gastric bypass.
OBJECTIVE
The relationship between obesity, weight reduction, and future risk of colorectal cancer is not well understood. Therefore, we compared mucosal biomarkers in normal weight individuals [body mass index (BMI), 18.5-24.9 kg/m(2)] with those in morbidly obese patients (BMI >40 kg/m(2)) before and 6 months after Roux-en-Y gastric bypass (RYGB).


METHODS
Rectal epithelial cell mitosis, crypt area, and crypt branching were measured following whole crypt microdissection. Apoptosis was measured by immunohistochemistry for neo-cytokeratin 18 on fixed tissue sections. Serum levels of C-reactive protein and cytokines were assayed in combination with quantification of mucosal proinflammatory gene expression by real-time RT-PCR.


RESULTS
Twenty-six morbidly obese patients (mean BMI, 54.4 kg/m(2)) had significantly increased mitosis, crypt area, and crypt branching (all P < 0.01) compared with 21 age- and sex-matched normal weight individuals (mean BMI, 22.5 kg/m(2)). Morbidly obese patients underwent a mean excess weight loss of 41.7% at a mean of 26 weeks after RYGB. Surprisingly, this was associated with a further increase in mitosis and decreased apoptosis of epithelial cells. At the same time, lower levels of serum C-reactive protein and interleukin-6 following RYGB were accompanied by a reduction in mucosal IL-6 protein content but elevated mucosal expression of other proinflammatory genes such as cyclooxygenase-1 and cyclooxygenase-2.


CONCLUSIONS
Mucosal biomarkers, accepted as indicators of future colorectal cancer risk, are increased in morbidly obese patients compared with normal weight controls. The hyperproliferative state that exists 6 months after RYGB may have important implications for long-term colorectal cancer risk in bariatric surgery patients.
Sainsbury
Anita
A
Section of Molecular Gastroenterology, Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Leeds LS9 7TF, United Kingdom.
Goodlad
Robert A
RA
Perry
Sarah L
SL
Pollard
Stephen G
SG
Robins
Gerard G
GG
Hull
Mark A
MA
D000328:Adult; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003106:Colon / Q000166:cytology*; D015179:Colorectal Neoplasms / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009767:Obesity, Morbid / Q000601:surgery*; D012007:Rectum / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D014408:Biomarkers, Tumor; D016207:Cytokines; D002097:C-Reactive Protein