Colorectal Cancer (Colon Carcinoma): Prevention

To prevent colon cancer (colorectal cancer), attention must be paid to reducing individual risk factors. Behavioral risk factors

  • Diet
    • High consumption of red meat, i.e., muscle meat of pork, beef, lamb, veal, mutton, horse, sheep, goat
      • Red meat is classified by the World Health Organization (WHO) as “probably carcinogenic to humans”, that is, carcinogenic.Meat and sausage products are classified as so-called “definite group 1 carcinogen” and are thus comparable (qualitatively, but not quantitatively) to the carcinogenic (cancer-causing) effect of tobacco smoking. Meat products include products whose meat component has been preserved or improved in flavor by processing methods such as salting, curing, smoking, or fermenting: Sausages, cold cuts, ham, corned beef, jerky, air-dried beef, canned meat. Daily consumption of 50 g of processed meats (equivalent to two slices of sausage) increases the risk of colon cancer by 18%, and daily consumption of 100 g of red meat by 17%.
      • Other studies suggest that iron ingested with meat may contribute to the increase in risk, as iron can promote the formation of harmful nitroso compounds in the body. Red meat or processed meats have a higher average iron content than poultry, so its consumption may not have affected colorectal cancer risk in this study.
      • A meta-analysis of several prospective cohort studies demonstrated an increased risk of colorectal cancer with very high meat consumption of beef and lamb. Pork was not associated with increased cancer risk.
      • Studies in rats with chemically-induced colon carcinoma (chemically-induced colon cancer) uniformly showed that dietary hemoglobin (red blood pigment) and red meat promote lesions (tissue damage) in the intestine as a precursor to carcinoma (tumor). The mechanism is still unknown, but heme iron has a catalytic (accelerating) effect on the endogenous (endogenous) formation of carcinogenic (cancer-promoting) nitroso compounds and on the formation of cytotoxic (cell-damaging) and genotoxic (genetic-damaging) aldehydes by means of lipid peroxidation (conversion of fatty acids, producing free radicals).
      • Other studies describe animal protein as an independent risk factor. With high-protein diets, increased proteins, peptides and urea pass into the colon. As an end product of bacterial metabolism ammonium ions are formed, which have a cytotoxic effect.
    • Too little fish consumption; inverse correlation between fish consumption and risk of disease.
    • Too little fruit and vegetable consumption
    • Heterocyclic aromatic amines (HAA) – these are formed exclusively when food (especially meat and fish) is heated (> 150 °C) and are considered carcinogenic. HAA develop mainly in the crust. The more browned the meat, the more HAA are formed. Individuals who have a high intake of HAAs have a 50 percent higher risk of developing polyps (adenomas) of the colon (large intestine), which are often precancerous lesions (precursors) for colon carcinoma (colon cancer).
    • Diet too rich in fats (high intake of saturated fatty acids of animal origin and of the polyunsaturated fatty acid linoleic acid (omega-6 fatty acid), contained in safflower, sunflower and corn oil) and low in complex carbohydrates and fiber.
    • Micronutrient deficiency (vital substances) – including insufficient supply of vitamins C and D, calcium (calcium binds promoters such as bile acids) and selenium; see Prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol (female: > 20 g/day; male: > 30 g/day); ≥ 50 g/day alcohol significant increase in colorectal cancer mortality (death rate).
    • Tobacco (smoking)
  • Physical activity
    • Physical inactivity
      • >14 hours of TV consumption per week as a measure of physical inactivity increases the likelihood of colorectal cancer by nearly 70% even at ages younger than 50
      • High cardiorespiratory fitness (average 13.0 MET ≈ 13 times basal metabolic rate) in middle age resulted in 44% reduced colorectal cancer mortality (colorectal cancer mortality rate)
      • “Frequent” (24% higher risk).
  • Psycho-social situation
    • High work stress: + 36% colorectal cancer (carcinomas of the colon (large intestine) and rectum (rectum)).
    • Night work – according to the assessment of the International Agency for Research on Cancer (IARC), shift work is considered “probably carcinogenic” (group 2A carcinogen).
  • Overweight (BMI ≥ 25; obesity):
    • For every 5 kg of weight gain, 5% increase in risk of colon cancer.
    • Overweight or obese teenagers in their teens (17 years):
      • 50 percent increased risk of later colon cancer for overweight or obese teens
      • 70 percent increased risk of rectal cancer for obese males; obese females about 100 percent increased
      • Obesity was not significantly associated with rectal cancer
    • Severe weight gain in young adulthood was associated with increased risk of colorectal cancer.
    • Increase in waist circumference and leptin receptor and high HbA1c levels.
  • Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type) – there is a high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)); increased abdominal fat has a strong atherogenic effect and promotes inflammatory processes (“inflammatory processes”)When measuring waist circumference according to the guideline of the International Diabetes Federation (IDF, 2005), the following standard values apply:
    • Men < 94 cm
    • Women < 80 cm

    The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

Environmental pollution – intoxications (poisonings).

  • Nitrate in drinking water (nitrate is converted in the body to nitrite and N-nitroso compounds); group of individuals exposed to the highest level of exposure at ≥ 16.75 mg/l had nearly 20% higher risk of colorectal cancer compared with individuals who had the lowest intake of nitrate in drinking water at < 0.69 mg/l (HR 1.16, 95% CI 1.08-1.25). CONCLUSION: The maximum limit of 50 mg nitrate per liter of drinking water under the EU Drinking Water Directive should be reconsidered.

Prevention factors (protective factors)

  • Genetic factors:
    • Genetic risk reduction depending on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Gene: SMAD7
        • SNP: rs4939827 in gene SMAD7
          • Allele constellation: CT (0.86-fold).
          • Allele constellation: CC (0.73-fold)
  • Adventist Health Study 2 (AHS-2):
    • Vegetarians had a 22% risk reduction for colon cancer compared with nonvegetarians
    • Pescovegetarians (definition: fish at least once a month, whereas all other meats less than once a month) had a risk reduction of:
      • 43% compared to non-vegetarians
      • 38% vs. semi-vegetarians (definition: a meat meal no more than once a week).
      • 30% vs. lacto-ovo vegetarians
  • High consumption of fruits and vegetables and whole grains influences colon cancer risk via intestinal flora (risk reduction: 57% for colorectal cancer with detection of F. nucleatum) – detection of genes of the intestinal bacterium Fusobacterium nucleatum in colon tumors is often associated with an aggressive course of cancer. Conclusion: a wholesome diet can protect against colorectal cancer.
  • High-fiber diet: According to a meta-analysis of 25 prospective observational studies, the risk of colorectal cancer decreases by 10% per 10 grams of fiber.
  • Nut consumption – reduction in the risk of colorectal cancer by 24%.
  • High versus low leisure-time physical activity is associated with lower risk of colon cancer (-15.05%; HR 0.84, 95% CI 0.77-0.91) and rectal cancer (-13%; HR 0.87, 95% CI 0.80-0.95).
  • Physical activity of 7 hours of brisk walking per week was associated with a 40% reduction in disease risk
  • For men, physical activity reduced colorectal cancer risk for the proximal colon (total group: -21%, men: -33%; after additional adjustment for waist circumference in a multivariate analysis, there was a significant risk for the proximal colon in men: -28%).
  • Subjects in the highest fitness category ≥ 12 MET:
    • 61% lower risk of colorectal cancer; incidence rates 0.27 and 0.97 per 1,000 person-years, respectively); risk of dying after a colorectal cancer diagnosis during follow-up was reduced by 89% for the fittest patients.
    • 77% lower risk of bronchial cancer than least fit participants; incidence rates: 0.28 and 2.00 per 1,000 person-years, respectively; risk of dying after a lung cancer diagnosis during the follow-up period was decreased by 44% for the fittest patients.
  • Medications
    • Antibiotic therapy: rectal cancers occur less frequently, but there is an increased risk for carcinomas of the anterior colon; for proximal colon carcinoma, an odds ratio of 1.32 (1.15 to 1.51) was found for a treatment duration of 31 to 60 days; odds ratio for rectal carcinoma for a treatment duration of more than 60 days was 0.84 (0.68 to 1.03); however, lifetime risk did not increase significantly: Men from 7% to 8% and for women from 6% to 7%.
    • Nonsteroidal anti-inflammatory drugs (NSAIDs)-at least 75 mg/d acetylsalicylic acid (ASA); greatest benefit was seen in tumors in the proximal colon
    • The effect of NSAIDs and acetylsalicylic acid (ASA) is genotype-dependent: Comparing 8,634 colon cancer patients and 8,553 healthy controls, the authors encountered two single nucleotide polymorphisms (SNPs):
      • rs2965667 is located on chromosome 12p12.3 near the gene MGST1: the gene encodes the enzyme “microsomal glutathione S-transferase 1,” which is involved in the metabolism of prostaglandin E (mediator of inflammatory responses in the body).
        • NSAID/ASS group: 34% decreased risk of colon cancer if they had TT genotype in rs2965667.
        • NSAR/ASS group: increased colon cancer risk by 89% if they had TA or AA genotypes (occur in only about 4% of cases in the population)
      • Rs16973225 on chromosome 15q25.2 near the gene for interleukin-16; a messenger released by T cells NSAR/ASS group: carriers of the AA genotype were 34 percent less likely to develop colon cancer
    • Acetylsalicylic acid (ASA) in Lynch syndrome: Relatively high-dose treatment with ASA for 2 years reduced the incidence of colorectal cancer in patients with Lynch syndrome in a randomized trial; the effect first became apparent after 5 years and could last up to 20 years.
    • Estrogen-progestin therapy: this may be able to reduce the risk of colorectal cancer; incidence rate (incidence of new cases) reduced by 19% after more than 40 years.

Tertiary prevention

Tertiary prevention of colon cancer is concerned with preventing progression or the occurrence of recurrence (recurrence of the disease). The following measure contributes to this goal:

  • Diet
    • High-fiber diet: per 5 grams of additional plant fiber consumed per day showed a 14% relative reduction in mortality risk (risk of death)
    • Tree nuts: Regular consumption of tree nuts had reduced the proportion of patients who had tumor regrowth after surgery and chemotherapy by 42%; the chance of surviving colorectal cancer increased by as much as 57% with an adjusted hazard ratio of 0.43 (0.25-0.74).
  • Coffee consumption
    • It is possible that daily coffee consumption of four cups or more improves the prognosis of stage III (advanced) colon cancer and reduces the risk of recurrence (recurrence of the disease). However, these observations were made as part of a study conducted for other reasons. Studies specifically investigating the effects of coffee consumption on existing colon cancer have yet to be conducted.
    • Drinking at least one cup of coffee daily is associated with a significant risk reduction for both death and progression (progression of disease) in patients with locally advanced or metastatic colorectal carcinoma; showed a dose-response relationship: effect increases with amount consumed (1, 2-3, or > 4 cups); also applies to decaffeinated coffee.
  • Medication
    • Patients who began taking acetylsalicylic acid (ASA) after a diagnosis of gastrointestinal malignancy (cancer of the gastrointestinal tract) had twice the 5-year survival rate in a retrospective cohort study (13,715 patients).
    • The median risk of developing metachronous neoplasia (occurrence of tumors at two separate time points) was reduced by:
      • Nonsteroidal anti-inflammatory drugs (NSAIDs) of the non-ASS type by just over 60%.
      • ASA in low dose (≤ 160 mg/day) by 30%.
      • High-dose ASA (≥ 300 mg/day) by 20%.
    • Acetylsalicylic acid (ASA) or other NSAID; intake before colorectal cancer.
      • 25% decreased all-cause mortality (all-cause mortality rate) (hazard ratio 0.75; 95 percent confidence interval 0.59-0.95)
      • 56% decreased risk of colorectal cancer (hazard ratio 0.44; 0.25 to 0.71)

      Intake after colorectal cancer diagnosis

      • All-cause mortality decreased by 36% (hazard ratio 0.64; 0.47-0.86)
      • Colorectal cancer-specific lethality (mortality) decreased by 60% (hazard ratio 0.40; 0.20-0.80)

      The tertiary preventive protective effect was limited to patients whose tumor expressed the wild-type (non-mutated variant) of the KRAS oncogene.

    • ASA therapy is effective for malignant colon tumors with low PD-L1 expression: patients who took ASA at least twice a week showed longer colon cancer-free survival when the tumor expressed PD-L1 at low levels (p < 0.001). Thus, PD-L1 may be a biomarker for adjuvant ASA therapy.
    • Patients with rectal cancer: downstaging (before surgery) with neoadjuvant chemoradiotherapy and, in addition, with a statin, with ASA, or metformin (in diabetic patients); furthermore, better progression-free survival and better overall survival with ASA use.
    • Women with hormone therapy (estrogens or estrogens/progesterone) before diagnosis of colon cancer: cancer-specific mortality was 29% and all-cause mortality was 34% lower than in those women without hormone therapy.