Basal Cell Carcinoma: Causes

Pathogenesis (disease development)

Basal cell carcinoma (BCC; basal cell carcinoma, BCC) is not only the most common cancer in humans, but also has the highest mutation rate of all cancers. This is due to DNA damage caused by UV radiation. In about 90% of all BCCs, the so-called Sonic Hedgehog (SHh) signal cascade is affected (mutations in the PTCH1, SMO or SUFU genes). BCCs arise de novo. i.e., they develop without a causative antecedent disease. Basal cell carcinoma arises from altered pluripotent basal epithelial cells (pluripotent: stem cells that have the ability to differentiate into almost all cell types of the three germ layers) that are unable to differentiate but continue to divide. They give rise to the epidermis, which renews itself repeatedly throughout life. UV radiation leads to mutation of the stem cells (exchange of cytosine for thymidine in the DNA) and thus to the tumor. Localization: Without early in situ precursors, mainly on light-exposed skin areas (facial skin, head, neck, décolleté). Furthermore, basal cell carcinomas may cluster in a nevus sebaceus (sebaceous nevus).

Etiology (causes)

Biographic causes

  • Genetic burden
    • Genetic risk depending on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: PADI6, XRCC1
        • SNP: rs25487 in gene XRCC1
          • Allele constellation: AG (2.0-fold).
          • Allele constellation: GG (2.0-fold)
          • Allele constellation: AA (0.7-fold)
        • SNP: rs801114 in an intergenic region.
          • Allele constellation: GG (1.28-fold).
          • Allele constellation: TT (0.78-fold)
        • SNP: rs7538876 in gene PADI6
          • Allele constellation: AA (1.28-fold).
          • Allele constellation: GG (0.78-fold)
    • Genetic conditions that predispose to increased UV sensitivity of the skin, such as:
      • Basal cell carcinoma syndrome (synonyms: Basal cell nevus syndrome; Fifth phakomatosis; Gorlin syndrome, Gorlin-Goltz syndrome; Nevoid basal cell carcinoma syndrome (NBCCS); nevus epitheliomatodes multiplex) – genetic disease with autosomal dominant inheritance, associated with the occurrence of numerous basal cell carcinomas in the third decade of life, keratocysts (keratocystic odontogenic tumor) in the second and third decades of life, and multiple other malformations (esp. skeletal system). Skeletal system) accompany
      • Bazex-Dupré-Christol syndrome – X-linked dominant inherited syndrome with generalized hypotrichosis (reduced number of hairs due to hair loss), diffuse alopecia (hair loss) and predisposition to early-onset basal cell carcinoma.
      • Forms of oculocutaneous albinism: albinism (Latin : albus’ ie white) – genetic disease with autosomal recessive inheritance: collective name for congenital disorders in the biosynthesis of melanins (which are pigments or dyes) and the resulting lighter skin, hair and eye color.
      • Rombo syndrome – genetic disease with probable autosomal dominant inheritance (genodermatosis).
      • Xeroderma pigmentosum (synonyms: Melanosis lenticularis progressiva, also moonshine disease or light shrinkage skin, abbreviated “XP”) – genetic disease with autosomal recessive inheritance, which is notable for various neoplasms of the skin caused by high sensitivity to light (photophobia).
  • Gender – predominantly male with an average age of 60 years with a clear tendency to manifest earlier.
  • Age – increasing age
  • Skin type – fair skin type (Fitzpatrick I-II)
  • Occupations – occupational contact with carcinogens such as arsenic/UV radiation.

Behavioral causes

  • Nutrition
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • UV radiation (sun/sunburn; solarium) (most important risk factor: intensive UV exposure).
    • Recreational or occupational exposure to UV radiation (UV-A rays (315-380 nm), UV-B rays (280-315 nm).

Disease-related causes

  • Basal cell carcinoma in own history
  • Basal cell nevus syndrome – genetic neurodermal syndrome; hallmarks of this disease are numerous superficial basal cell carcinomas, which in the further course turn into true basal cell carcinomas.
  • Chronic degenerative dermatoses (skin diseases).
  • Chronic inflammatory dermatoses
  • Chronic, mechanically stressed scars
  • Chronic fistulizing (fistula forming) skin diseases.
  • Chronic ulcerating (ulcerated) skin diseases or chronic ulcers (ulcers).
  • Lupus vulgaris – chronic skin tuberculosis.
  • Scars (rare)
  • Nevi sebacei (rare) – sebaceous nevus
  • X-ray dermatitis – skin reaction to X-ray exposure.

Medication

Radiotherapy

  • Areas of irradiated skin (so-called chronic radioderma).

Environmental pollution – intoxications (poisonings).

  • Occupational contact with carcinogens such as arsenic.
  • Therapeutic ionizing radiation (esp. in childhood cancer).
  • UV radiation (chronic and intermittent UV exposure: sun; solarium).