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Increased Colorectal Epithelial Cell Proliferation and Crypt Fission Associated with Obesity and Roux-en-Y Gastric Bypass

¹ Section of Molecular Gastroenterology, Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital; ² Department of Obesity Surgery, St. James's University Hospital, Leeds, United Kingdom; and ³ Histopathology Unit, London Research Institute, Cancer Research UK, London, United Kingdom

Requests for reprints: Mark Hull, Section of Molecular Gastroenterology, Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Leeds LS9 7TF, United Kingdom. Phone: 44-113-343-8650; Fax: 44-113-343-8702. E-mail: M.A.Hull{at}leeds.ac.uk

Background and Aims: 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/m²] with those in morbidly obese patients (BMI >40 kg/m²) 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/m²) 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/m²). 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. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1401–10)