Colon Polyps (Colonic Adenoma): Causes

Pathogenesis (disease development)

Adenoma-carcinoma sequence

Most colon carcinomas develop over years from adenomas – so-called adenoma-carcinoma sequence. An accumulation of mutations (changes in genetic material) are responsible.The adenoma peak occurs circa 10 years before the onset of carcinoma. As the size of the adenoma increases, so does the risk of developing invasive carcinoma. The causes of the gene alterations that are ultimately responsible for the transition of a normal intestinal mucosal cell into a cancerous cell cannot usually be precisely identified. It is a multifactorial event. Depending on the exact histologic classification, the tendency for degeneration varies. In villous adenoma, degeneration occurs in up to 30% of cases. In tubular adenoma, this is true only for up to five percent. In addition to the adenoma-carcinoma sequence, other pathways of sporadic carcinogenesis exist:

  • Serrated carcinogenesis (precursor lesion: “sessile serrated adenoma (SSA)” [typically > 5 mm, flat raised and located in the right-sided colon]Note: SSAs are relatively difficult to detect endoscopically; therefore, may be a major cause of so-called interval carcinomas.
  • Mixed type combining molecular genetic characteristics of the other two carcinogenic pathways [precursor lesions: “traditional serrated adenoma (TSA)” or villous adenoma].

Etiology (causes)

Biographical causes

  • Genetic burden
    • Hamartomatous polyposis syndromes such as.
      • Familial juvenile polyposis (FJP) – clinical picture characterized by the presence of many “juvenile polyps” (polyps in childhood); inheritance is autosomal dominant; polyps become symptomatic by recurrent colicky abdominal pain attacks
      • Peutz-Jeghers syndrome (synonyms: Hutchinson-Weber-Peutz syndrome or Peutz-Jeghers hamartosis) – genetic disorder with autosomal-dominant inheritance; associated with gastrointestinal polyposis (occurrence of numerous polyps in the gastrointestinal tract) with characteristic pigmented spots on the skin (especially in the middle of the face) and mucous membranes; clinical picture: Recurrent (recurrent) colicky abdominal pain; iron deficiency anemia; blood accumulation on stool; possible complications: Ileus (intestinal obstruction) due to invaginations of a polyp-bearing intestinal segment.
    • Familial adenomatous polyposis (FAP; synonym: Familial polyposis) – is an autosomal dominant inherited disease. This leads to the occurrence of a large number (> 100 to thousands) of colorectal adenomas (polyps). The probability of malignant degeneration is almost 100% (on average from the age of 40).
    • MUTYH-associated polyposis (MAP) – gene: MUTYH; tumor spectrum: colon carcinoma (colon cancer), colon adenomas.
  • Age – increasing age: 20-30% of those over 60 years and 75% of those over 70 years have adenomas of the colon.

Behavioral causes

  • Nutrition
    • 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
    • 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, on average, a higher iron content than poultry, so its consumption may not have affected colorectal cancer risk in this study.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. In 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 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).
    • Micronutrient deficiency (vital substances) – insufficient supply of vitamin D and calcium (calcium binds promoters such as bile acids); see Prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol (woman: > 20 g/day; man: > 30 g/day) – especially with reduced folic acid intake!
    • Tobacco (smoking) (An association between cigarette smoking and colorectal adenomatous polyps has already been demonstrated in numerous studies. A meta-analysis shows that such precursors of colorectal cancer are also more aggressive in smokers).
  • Physical activity
    • Physical inactivity
  • Overweight (BMI ≥ 25; obesity).
    • Severe weight gain (mean 17.4 kg) versus stable overweight: summed OR for colorectal adenoma occurrence was 1.39 (95% CI 1.17-1.65)
    • Each 5 kg weight gain increased the risk of adenomas by 7% (2-11%; n = 7 studies)
  • Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type)-there is a high waist circumference or an increased waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)); Each 25 cm2 increase in visceral fat volume is associated with a 13% increase in adenoma riskWhen waist circumference is measured according to the International Diabetes Federation guideline (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.

Disease-related causes

  • Cronkhite-Canada syndrome (CCS) – gastrointestinal polyposis syndrome (polyps in the gastrointestinal tract), which, in addition to the clustered occurrence of intestinal polyps, leads to changes in the skin and skin appendages, such as alopecia (hair loss), hyperpigmentation and nail formation disorders, among others; Symptoms do not appear until after the age of fifty; initial symptoms include watery diarrhea (diarrhea), loss of taste and appetite, abnormal weight loss, and hypoproteinemia (decreased levels of proteins in the blood); sporadic occurrence

Medications

  • 1,200 mg calcium and 1,000 IU/day vitamin D3 (treatment 3-5 years): during the treatment phase, no effect of calcium or vitamin D on the formation of sessile serrated (“sawtooth”) adenomas (SSAs) could be demonstrated; 6 to 10 years after the start of treatment, accumulation of SSAs: women and smokers were at higher risk if they had taken calcium supplements.Note: SSAs probably have the same risk as adenomatous polyps of developing into cancer.