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The Romans believed that illnesses stemmed from the “heart” but the Greeks from the gut. Were the Greeks right after all? Dietary influence on colorectal cancer (CRC) has been extensively studied but with very little agreed consensus. Pederson et al (Gut 2003;52:861–7) reawaken this idea by showing a causal relationship between alcohol and rectal cancer while Dray et al (Gut 2003;52:868–73) conclude that prolonged survival post curative surgery for CRC was associated with high energy intake. What about fibre?
Burkitt was the first to attribute CRC to fibre deficiency1 which was later challenged by Cleave as excess sugar or “the saccharine disease”.2 A wealth of epidemiological and interventional studies have presented conflicting views. Particularly damning were a clutch of papers in 2000 showing little or no benefit of fibre on adenoma formation.3,4 Two recent papers5,6 add significantly to the debate. Both have shown a protective role of fibre on distal colonic adenomas and on colorectal cancer, respectively. Hence the question arises, why the difference?
The earlier interventional studies3,4 showing no benefit were of a much smaller size in a single population and had a shorter duration of follow up. Adenoma recurrence was used as an end point, presumably thereby skewing the data towards a population with as yet phenotypically silent premalignant mutations. This has implications as the time frame from exposure of nutritional factors which influence critical steps in the molecular and cellular development of CRC is quite long. Furthermore, the total quantity of fibre (g/day) consumed was low and the types of fibre studied were different. Non-starch polysaccharides (NSP) are fermented by gut microflora to produce three main short chain fatty acids (butyric acid, acetic acid, and propionic acid). These compounds have a range of properties and functions according to their “fermentability”—non-fermentable fibres have poor antitumour potential in in vivo models.7 In contrast, poorly fermented fibres afford protection by yielding fermentation products along the entire length of the colon. Therefore, how can we put fibre confidently back on the menu?
What is needed is a large varied population study correlating molecular/cellular markers and CRC with dietary fibre. In addition, a distinction must be made between colon and rectal cancer. Apart from having different embryological derivations, right sided colonic cancer and left sided colonic cancer (distal to splenic flexure) exhibit differences in incidence according to geographic region, age, and sex.8 Secondly, the problem, as in previous works, is studying NSP as a homogenous group. Butyric acid is the main short chain fatty acid (SCFA) produced in millimolar quantities in the colonic lumen. It has a number of functions in the colon: (i) as a fuel source for colonocytes; (ii) a survival factor for healthy cells; (iii) a stimulator of proliferation; and (iv) it suppresses carcinogenesis in a rat model. Butyrate therefore has a multifactorial role in the determination of bowel health. Examining specific SCFAs in stool or biomarkers of their utilisation therein, is likely to provide more consistent observations.
Finally, the study of dietary fibre using colorectal adenomas as an end point in interventional studies is questionable. This is based on the assumption that adenomas are an adequate surrogate marker for colorectal cancer. In light of studies showing highly different ratios of adenoma and carcinoma formation between populations,9,10 implying distinct aetiology and triggering events, this is a particularly unsafe assumption. The EPIC study has justified renewal of interest in the protective role of fibre in the colon. More carefully designed intervention studies may put it back on the menu.
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