EPA and colorectal cancer, reducing the risks – Dr Nina Bailey

Cancer of the large bowel or colorectal cancer (CRC) is currently the third most common cancer worldwide after lung and breast, with almost 60% of all colorectal cancers occurring in developed countries.  It is estimated that around 106 new cases of colorectal cancer are diagnosed each day in the UK, and in 2007 there were 38,608 new cases of large bowel cancer registered in the UK: around two-thirds in the colon and one-third in the rectum (ONS 2010).

Certain factors increase a person’s risk of developing the disease, including age, with 84% of cases arising in people who are 60 years or older.   While cases before the age of 50 are uncommon, a family history of early colon cancer significantly increases risk.  For example, Familial adenomatous polyposis (FAP) carries a near 100% risk of developing colorectal cancer by the age of 40 if untreated.

Individuals who have a history of colorectal cancer, such as familial adenatous polyposis (FAP), within their family are at increased risk of developing CRC which carries a near 100% risk of developing colorectal cancer by the age of 40 if untreated. FAP is caused by mutations in a specific gene called the adenomatous polyposis coli (APC) gene.  In normal individuals, the APC protein derived from this gene helps control how often a cell divides, and how that cell then functions in regards to its movement within tissues.   A mutation in the APC gene is the earliest detectable molecular abnormality in CRC, and the mutation results in the production of a shorter than normal protein product which fails to regulate cell division, extremely relevant when considering the invasiveness of cancers.  The result of uncontrolled growth of cells due to genetic mutations (many genes are involved in the initiation and progression of cancer) is the formation of small tissue projections called polyps, and the development of such polyps are regarded as the precursor of colorectal cancer.  It is believed that as many as 70% of colorectal cancers are preceded by the formation of a benign colonic polyp.

CRC is a common cancer in many western societies.   The role of diet in the development of CRC has long been recognised, and extensively studied, although the results are not clear-cut.  However, there appears to be a link with diets that are high in fat and red meat, but low in fibre and sea food, with an increased CRC risk.  The protective role associated with fish consumption has been suggested to be, in part, due to  ability of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) to cause cells with mutations to undergo a process called ‘apoptosis’, or programmed cell death, which prevents the mutation from being passed on.

Use of EPA has recently been shown to exhibit strong chemopreventive effects in a study of patients with familial adenomatous polyposis (FAP), according to findings published in a recent edition of the journal Gut (West et al, 2010). The study saw 55 patients with FAP aged 18 years and older randomly assigned either the highly purified form of EPA (2g daily) or matching placebo for 6 months, after which time polyp size and frequency were observed. There was a 2.6-fold increase on average in mucosal EPA levels in the EPA group, and most significantly a reduction in both rectal polyp number and size when compared to the placebo group.   Polyp diameters increased by 17.2% during placebo treatment but decreased by 12.6%, and mean 22.4% reduction in polyp numbers during the EPA treatment.  These extremely encouraging effects were described as similar to those observed with the drug ‘Celecoxib’ a selective cyclo-oxygenase-2 inhibitor commonly used in the treatment of FAP.  Consequently, EPA is being investigated as a CRC chemoprevention agent that, unlike conventional drugs such as Celecoxib which has potential adverse cardiovascular side effects, has limited (if any) unpleasant side effects (Lynch, 2010).

Lynch PM. Eicosapentaenoic acid and chemoprevention of FAP. (2010) Gut. 59:871-3.

Office for National Statistics, Cancer Statistics registrations: registrations of cancer diagnosed in 2007, England. 2010

West NJ, Clark SK, Phillips RK, Hutchinson JM, Leicester RJ, Belluzzi A, Hull MA. (2010)

Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut. 59:918-25.

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