Colorectal Cancers (CRC): Risk Factors and Protective Factors: What’s Myth & What’s N

This article will specifically focus on well known and not so well known risk factors for the development of CRC and adenomas. Also, since we live in an era when substantial misinformation is apparently legally disseminated in the field of preventive medicine by various stake holders, it is appropriate to identify protective factors scientifically proven to work towards prevention of CRC and adenomas.

Colorectal cancers (CRC) are the 3rd largest cause of death in Australia after cardiovascular diseases and lung cancer. Over 3,800 patients died of CRC in Australia in 2006.

There has been a 2.4-3 fold decline in USA between 1988-2005 attributed to screening. While there has been demonstrable decline in CRC diagnosis in the left side of the colon, incidence of CRC in the right side of the colon remains the same. Incidence of CRC is 10 fold higher in North America, Australia and Western Europe compared to Africa and Asia attributed to dietetic factors interacting with genetic predisposition.


Genetic Syndromes: Familial adenomatous polyposis (FAP) syndrome and its variants (Gardner’s ,Turcot’s. attenuated FAP syndromes) account for less than 1% of CRC. Hereditary non-polyposis colorectal cancer (HNPCC) is the most prevalent of genetic syndromes yet accounts for less than 5% of all CRC.

Personal or family history of CRC or large(≥ 10mm) villous or tubulovillous adenomas constitute greater risk of 10-30% of all CRC.

Average risk patients are those with no personal or family history of CRC and is the largest group with 65-85% of all CRC. This is the group in which dietetic and environmental factors play a major role. Inflammatory bowel disease(IBD): Extent and duration of IBD determine risk. With ulcerative colitis, risk increases 5-15 fold for pancolitis and 3 fold for left sided colitis 8 or more years after the initial diagnosis. Pancolitis associated with Crohn’s disease may have similar risk to ulcerative Colitis but less data is available.

Diabetes (type 2) and insulin resistance: A large meta-analysis of 15 studies suggest a 30% increase in CRC risk in these patients compared to non-diabetics. Cholecystectomy: A small number (incidence ratio of 1.16) has been described for development of CRC in the right side of the colon in patients who had cholecystectomy.

Alcohol: An analysis of 8 cohort studies puts the relative risk at 1.41 for develop- ing CRC in those consuming more that 45gms of alcohol a day.

Obesity: Two large cohort studies demonstrate 1.5 fold increased risk of CRC in the obese compared to the normal individuals (BMI:18-24.9 kg/m2). Also the obese has higher risk of dying from CRC after diagnosis.

Other risk factors:

  •  Coronary artery disease has been associated with increased risk of CRC /adenoma.
  •  Smoking (tobacco) is related to risk of CRC, adenoma, dysplasia and mortality.
  •  Ureterocolic anastomosis is associated with risk of colorectal neoplasia.
  •  Acromegally patients get more CRC & adenoma (22% vs 8% of controls).
  • Long-term consumption of processed or red meat as opposed to lean meat has been linked to CRC.
  •  Relationship between caffeine intake and CRC is unresolved.
  •  Relationship between BRCA1 gene mutation positive breast cancer patients and subsequent development of CRC is unresolved although some oncologists feel these patients should have colonoscopy.
  • Prostate cancer patients who received radiation have increased risk of rectal neoplasia.
  •  Prior treatment of Hodgkin’s lymphoma is associated with increased risk of CRC.
  • Some reports associate HIV infection with increased risk of CRC.
  • Association of Barrett’s oesophagus, H. pylori,, Streptococcus Bovis, JC Virus and Human papilloma Virus infections to CRC remains inconclusive.PROTECTIVE FACTORS FOR CRC:

Fibre: Despite popular enthusiasm and a large number of studies, the role of fibre remains unclear in the prevention of CRC. Prospective interventional studies are awaited.
Resistant Starch: Role of this is inconclusive: further trials are awaited.
Folic Acid: Use of folic acid for the prevention of CRC remains controversial. While laboratory studies demonstrate anti-cancer effect of folic acid, most clinical studies have failed to demonstrate a protective effect against CRC/adenoma.

Vitamin B6: Pyridoxine may have a protective effect as per the large nurses health study .
Calcium: Studies , by and large, support a role for calcium supplementation for the prevention of CRC and is recommended by the American College of Gastroenterology.
Magnesium supplements may reduce CRC and adenomas (Swedish Study) but be aware of diarrhea as a side effect.
Garlic requires further evaluation.
Fish consumption is associated with lower risk of CRC.

Physical Activity , either occupationally or in leisure time, is associated with reduced risk of CRC. Aspirin & NSAID are protective against development of CRC and adenomas.

Postmenopausal Hormone Therapy: Although combined oestrogen and progesterone therapy has ben- eficial effect on development of CRC, there are concerns relating to its effect on development of breast neoplasia on the long term.
DFMO(difluromethylornithine) & Sulindac: This combination has a dramatic effect on reduction of the rate of adenoma formation yet has significant ,albeit, mild mostly permanent subclinical changes in the audiogram. Further studies are awaited.
Antioxidants: Data from a meta-analysis of 8 controlled trials failed to show any beneficial effect for CRC or adenomas, either occupationally or in leisure time, is associated with reduced risk of CRC. Aspirin & NSAID are protective against development of CRC and adenomas.


  •  While screening with FOB and colonoscopy for average risk patients and those with a family history should continue, awareness of other risk factors such as inflammatory bowel disease, type 2 diabetes, obesity, smoking and combination of these risk factors should help direct specific individualized screening tests for CRC.
  •  In an era of significant misinformation regarding preventive health, it is important to know what dietetic factors and supplements have proven protective effect on development and recurrence of CRC and adenomas respectively e.g., low red meat and high fish content in diet, calcium, magnesi- um, vitamin B6, aspirin and NSAIDs (Sulindac).
  •  Although the evidence for high fibre intake is not there yet, I believe it is reasonable to recommend a diet high in cruciferous vegetables, high in fruits, low in fat, low in non-lean red meat and high in fish content.Recommended Reading:

    Ahnen DJ & Macrae FA :,2009 Choo L & Norton I :MedicineToday: 11(5),page 25, May 2010



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