Pathogenesis (disease development)
Bronchial carcinoma develops through several stages, in which carcinogens (carcinogenic substances) such as nicotine, but also so-called tumor promoters play a role. The so-called inhaled carcinogens (inhaled carcinogenic substances) are considered to be the causes of lung cancer:
- Arsenic
- Asbestos (asbestosis)
- Beryllium
- Cadmium
- Chromium VI compounds
- Diesel exhaust (due topolycyclic hydrocarbons, PAH).
- Halogenated ethers (“haloethers”, haloether), especially dichlorodimethyl ether.
- Inhalation of coal dust (miners).
- Nickel (nickel dust)
- Polycyclic aromatic hydrocarbons (PAHs), e.g. benzene, benzo(a)pyrene.
- Quartz dust (dusts containing crystalline silicon dioxide (SiO2); silicosis).
- Radioactive substances (uranium, radon).
- Radon (5% of all bronchial carcinoma deaths; according to the Federal Office for Radiation Protection).
- After smoking, involuntary inhalation of radioactive radon in the home is the most common trigger of bronchial carcinoma.
- Mustard gas
- Tungsten- and cobalt-containing carbide dusts
- Fine dust
- Tobacco smoke
For smokers, the risk of developing lung cancer increases with the cumulative (accumulated) daily dose.
Etiology (causes)
Furthermore, the following causes of lung cancer are known:
Biographic causes
- Genetic burden – if one parent has the disease, the risk increases two- to threefold
- Genetic risk dependent on gene polymorphisms:
- Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
- Genes: DCAF4, HYKK
- SNP: rs12587742 in the gene DCAF4
- Allele constellation: AG (elevated) (confirmed so far only for the European population).
- Allele constellation: AA (increased) (confirmed so far only for the European population).
- SNP: rs8034191 in the HYKK gene.
- Allele constellation: CT (1.27-fold for smokers).
- Allele constellation: CC (1.80-fold for smokers).
- Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
- Genetic risk dependent on gene polymorphisms:
- Workplace – approximately 5% of all bronchial carcinomas are due to occupational carcinogens (see above).
- Socioeconomic factors – low socioeconomic status.
Behavioral causes
- Nutrition
- Too little fruit and vegetable consumption (scientifically, the role of a deficiency of vitamin A is not fully understood).
- Micronutrient deficiency (vital substances) – see prevention with micronutrients.
- Insufficient supply of vital substances
- Consumption of stimulants
- Alcohol (women more than 10 g per day; men more than 20 g per day) – promotes the development of bronchial carcinoma, among other things.
- Tobacco (smoking, passive smoking).
- Approximately 85% of all bronchial carcinomas occur in smokers!
- The risk of a man who smoked two packs a day for 20 years is 60 to 70 times that of a non-smoker. After quitting smoking, the risk decreases, but never again reaches the level of a non-smoker.
- A quarter of all smokers who are carriers of the “breast cancer gene” BRCA2 develop the disease during their lifetime.
- Physical activity
- Physical inactivity; high cardiorespiratory fitness (average 13.0 MET ≈ 13 times basal metabolic rate) in middle age resulted in 55% reduced lung cancer mortality (lung cancer mortality rate)
- Psycho-social situation
Causes due to illness
- Chronic obstructive pulmonary disease (COPD) – especially in combination with smoking.
- Lung scars, which can occur, for example, after tuberculosis or surgery.
- Second tumor risk is increased after chemotherapy wg :
- Non-Hodgkin’s lymphoma (NHL) – skin cancer (except melanoma) and lung cancer.
Laboratory diagnoses – laboratory parameters considered independent risk factors.
- Platelets (thrombocytes) – each 100 x 109/l increase in platelet count is associated with a 62% higher risk of developing non-small cell lung cancer (odds ratio [OR]: 1.62; 95% confidence interval: 1.15-2.27; p = 0.005) (data based on a Mendelian radomization with data from nearly 50,000 Europeans)
Medication
- ACE inhibitors-angiotensin-converting enzyme metabolizes bradykinin, an active vasodilator, in addition to angiotensin I; bronchial carcinomas express bradykinin receptors; bradykinin may stimulate vascular endothelial growth factor release (= promote angiogenesis and thus tumor growth). In patients receiving ACE inhibitors, the incidence was 1.6 per 1,000 person-years versus 1.2 per 1,000 person-years in the other hypertensive patients; ACE inhibitor therapy increased the risk relatively by 14%.ACE inhibitors and lung cancer: causal relationship not established after evaluation by the European Medicines Agency.
- Selective serotonin reuptake inhibitors (SSRIs) ?
- Tricyclic antidepressants (TCAs) ?
Environmental exposure (including workplace exposures) – Intoxications (poisonings).
- Occupational contact
- With carcinogens – e.g., asbestos, man-made mineral fibers (MMMFs), polycyclic aromatic hydrocarbons (PAHs), arsenic, chromium VI compounds, nickel, halogenated ethers (“haloethers”), especially dichlorodimethyl ether, radioactive materials, etc.
- Coke oven raw gases
- Handling tar and bitumen (road construction).
- Inhalation of coal dust (miners).
- Inhalation of nickel dust, quartz dust (dusts containing crystalline silica (SiO2)).
- Arsenic
- Men: mortality risk (risk of death)/relative risk (RR) 3.38 (95 percent confidence interval 3.19-3.58).
- Women: Mortality risk/relative risk 2.41 (95-percent confidence interval 2.20-2.64).
- Tetrachloroethene (perchloroethylene, perchloro, PER, PCE)?, in women.
- Diesel engine emissions (DME)/diesel exhaust (due topolycyclic hydrocarbons, PAH).
- Air pollutants: particulate matter (due to car exhaust, combustion processes in industry and domestic heating) – already particulate matter concentration below the European limit increases the likelihood of developing lung cancer
- Ionizing rays
- Radon – after smoking, involuntary inhalation of radioactive radon in the home is the most common trigger of lung cancer; it is responsible for about 5% of all lung cancer deaths in Germany