Role of Resistant Starch in Colorectal Cancer Prevention: A Prospective Randomised Controlled Trial

Abstract

Purpose: Colorectal cancer (CRC) is the second most common cause of cancer related death in the western world. Resistant starch (RS), defined as starch that resists digestion in the small intestine of a healthy individual, gets converted to butyrate following bacterial fermentation in the colon. Butyrate is shown to have potent anti-neoplastic effects on colon cancer cells in vitro. This study investigated the anti-neoplastic effects of RS in patients with CRC and its potential role of as a chemo-preventive agent. Methods: A total of 65 (36 male) sporadic CRC patients were randomised to treatment (40 gm/ day) with RS or ordinary starch (OS) for 2–4 weeks. Pre-treatment and post-treatment biopsies were obtained from tumour and normal mucosa and the effects of the intervention on cell proliferation and expression of cell cycle regulatory genes CDK4 and GADD45A (using real time RT-PCR) were investigated. Results: The proportion of mitotic cells in the top half of the crypt (which is a valid pre-malignant marker used to assess response to chemo-preventive trials) was markedly reduced following RS treatment as compared with OS treatment (P= 0.028) (Fig. 1). There was no effect of RS treatment on crypt dimensions or tumour proliferation index. The expression of key cell cycle regulatory gene CDK4 was upregulated (P < 0.01) while that of GADD45A was down regulated (P < 0.001) in the tumour tissue compared with normal flat mucosa. RS treatment for up to 4 weeks in CRC patients tended to increase CDK4 expression (P= 0.07) in tumour tissue. Expression of GADD45A, which was suppressed in cancer, was significantly upregulated (P= 0.048) following RS treatment (Fig. 2). Conclusion: RS modulates the colonic crypt cell kinetics and has potential as a chemo-preventive agent against CRC. The differential expression of key cell cycle regulatory genes may play a role in these cellular effects of RS.[figure1]Figure