Stomach Cancer (Gastric Carcinoma): Causes

Pathogenesis (development of disease)

Gastric carcinoma is an adenocarcinoma in more than 90 percent of cases, i.e., a malignant tumor arising from glandular tissue.Carcinoma in situ refers to the early stage of a tumor that does not penetrate the basement membrane, i.e., is without invasive tumor growth. Early gastric carcinoma is said to occur when it crosses the basement membrane but is confined to gastric mucosa (gastric mucosa/mucosal type) or to the mucosa and submucosa (submucosal connective tissue/submucosal type), regardless of surface extent and regardless of lymph node status.Nitrates ingested through food, which are converted to nitrites by bacteria (saliva/stomach), are considered particularly dangerous. These form nitrosamines with secondary amines, which have a genotoxic (“genetic damage”) and mutagenic effect. The bacterium Helicobacter pylori is also thought to contribute to this transformation. The infection contributes to accelerated stem cell regeneration within the gastric glands, increasing the number of cells with stem cell potential and with them the risk of pathological change.Furthermore, intestinal metaplasia (i.e. the normal mucosa is replaced by mucosa that partially or completely corresponds to the structure of the mucosa of the small or large intestine) is thought to cause neoplasia (new formation). In the presence of intestinal metaplasia, the patient may no longer benefit from Helicobacter pylori eradication (elimination of the pathogen).Gastric carcinoma may metastasize (daughter tumors) by direct expansion or else via lymphatic and hematogenous spread (i.e., via the lymphatic and blood pathways). In a Swedish population-based cohort study (405. 172 patients), the risk of gastric carcinoma was assessed based on baseline histologic (histological) findings; this yielded a carcinoma risk of 1:256 in normal mucosa (mucosa), 1:85 in gastritis (gastric mucosal inflammation), 1:50 in atrophic gastritis (chronic gastric mucosal inflammation with slow destruction of the same), 1:39 in intestinal metaplasia (cf. Above), and 1:19 in dysplasia (malformations).

Etiology (Causes)

Biographic causes

  • Genetic burden
    • By parents, grandparents (about 3.7 times greater risk of disease if a first-degree family member – i.e., parents, children, siblings – already has gastric cancer)
    • Genetic diseases
      • Associated with familial cancer syndromes (rare), eg.
        • Hereditary diffuse gastric carcinoma (HDGC).
        • Familial adenomatous polyposis (FAP; synonym: Familial polyposis) – is an autosomal dominant inherited disorder. This leads to the occurrence of a large number (> 100 to thousands) of colorectal adenomas (polyps). The probability of malignant (malignant) degeneration is almost 100% (average from the age of 40).
        • HNPCC (Engl. heredetery non-polyposis colorectal cancer; hereditary colorectal carcinoma without polyposis, also known as “Lynch syndrome“) – genetic disease with autosomal dominant inheritance; associated with early-onset colorectal carcinomas (cancer of the colon or rectum) and possibly other tumor diseases).
        • Juvenile polyposis syndrome
      • Hemochromatosis (iron storage disease) – genetic disease with autosomal recessive inheritance with increased deposition of iron as a result of increased iron concentration in the blood with tissue damage; secondary diseases: Liver cirrhosis (liver shrinkage), hepatocellular carcinoma, gastric carcinoma, cardiomyopathy (heart muscle disease), arthropathy of large joints.
  • Blood group – non-0 blood groups (blood group A, B, AB) (1.09 times increased risk).
  • Age – older age (non-cardiac cancer/no tumor in gastric inlet).
  • Socioeconomic factors – low socioeconomic status (noncardiac cancer/no tumor in gastric inlet).

Behavioral causes

  • Nutrition
    • Too little fruit and vegetable consumption
    • Too little fish consumption; inverse correlation between fish consumption and risk of disease.
    • Diets high in nitrates and nitrites, such as cured or smoked foods:Nitrate is a potentially toxic compound: Nitrate is reduced to nitrite in the body by bacteria (saliva/stomach).Nitrite is a reactive oxidant that reacts preferentially with the blood pigment hemoglobin and converts it into methemoglobin. Furthermore, nitrites (also contained in cured sausage and meat products and ripened cheese) form nitrosamines with secondary amines (contained in meat and sausage products, cheese and fish), which have genotoxic and mutagenic effects. They favor, among other things, the development of stomach cancer.The daily intake of nitrate is usually about 70% through the consumption of vegetables (lettuce and lettuce, green, white and Chinese cabbage, kohlrabi, spinach, radish, radish, beet), 20% from drinking water (nitrogen fertilizer) and 10% from meat and meat products and fish.
    • Benzo(a)pyrene is considered a risk factor for gastric carcinoma (stomach cancer). It is formed during toasting and charcoal grilling. It is found in all grilled, smoked or burnt foods.Cigarette smoke also contains benzo(a)pyrene, which in turn can lead to bronchial carcinoma.
    • Eating foods that may be affected by the mold Aspergillus flavus or Aspergillus parasiticus. These molds produce aflatoxins, which are carcinogenic.Aspergillus flavus is found in peanuts, pistachios and poppy seeds; Aspergillus parasiticus is found in peanuts.
    • Sodium or salt intake: there is debate as to whether long-term high sodium or salt intake leads to an increased risk of gastric cancer. For example, there is circumstantial evidence that atrophic gastritis (gastritis of the gastric mucosa) develops more frequently with high salt intake. In addition, carcinogens can penetrate the barrier of the gastric mucosa (stomach lining) more easily when high concentrations of table salt are present in the stomach.
    • Micronutrient deficiency (vital substances) – see prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol (female: > 20 g/day; male: > 30 g/day) (non-cardiac cancer/no tumor in gastric inlet)
      • Heavy drinkers (>4 to 6 drinks): 1.26-fold increased risk; very heavy drinkers (>6 drinks): 1.48-fold increased risk
      • Only individuals who did not have H. pylori-specific IgG antibodies increased gastric cancer risk by heavy drinking (alcohol for > 30 years, ≥ 7 times per week, or amount ≥ 55 g on a single occasion (binge drinking))
    • Tobacco (smoking); about 3-fold increased risk of disease [adenocarcinomas in the transition from the stomach to the esophagus].
  • Psycho-social situation
    • Night service (+ 33%)
  • Overweight (BMI ≥ 25; obesity); adenocarcinomas in the transition from the stomach to the esophagus (+ 80%).

Disease-related causes

  • Chronic-active gastritis (gastritis)/type B gastritis/bacterial gastritis caused by the bacterium Helicobacter pylori; starting point for the development of more than 90% of all gastric carcinomas (eradication/complete elimination of the pathogen from the body has a carcinoma-protective effect).
  • Chronic atrophic type A gastritis (intestinal type of gastric carcinoma; autoimmune gastritis).
  • Epstein-Barr virus infection (infectious mononucleosis; Pfeiffer’s glandular fever) – in people suffering from immunodeficiency (immunodeficiency) can develop, among other things, gastric carcinoma.
  • Gastroesophageal reflux disease – reflux (Latin refluere = flow back) of acid gastric juice and other gastric contents into the esophagus (esophagus) [adenocarcinomas in the transition from the stomach to the esophagus].
  • Gastric polyps, adenomatous – mucosal outpouchings in the area of the stomach.
  • Ménétrier’s disease (giant fold gastritis).
  • Pernicious anemia – most common subtype of vitamin B12 deficiency anemia (anemia) (non-cardiac cancer/no tumor in the entrance of the stomach).

Operations

  • Condition after partial gastric resection (partial removal of the stomach) (non-cardiac carcinoma/no tumor in the entrance of the stomach).

Environmental exposure – intoxications (poisonings).

  • Ingestion of nitrosamines
  • Benzpyrene – found in exhaust fumes, smoke and tar. It is considered a risk factor for gastric cancer, among other things.