Renal Cell Carcinoma (Hypernephroma): Causes

Pathogenesis (disease development)

Renal cell carcinoma usually involves chromosome 3p deletions (genetic alterations). This causes an amplification of several factors that promote tumor growth. These factors include VEGF (vascular endothelial growth factor) and PDGF (platelet-derived growth factor).

Etiology (Causes)

Biographic Causes

  • Genetic burden from parents, grandparents (about 3%).
    • Genetic diseases
      • Birt-Hogg-Dubé syndrome (BHDS) – genetic disorder with autosomal dominant inheritance; germline mutations in the FLCN gene have been found in families with BHDS; clinical presentation: Skin lesions, renal tumors, and lung cysts, possibly associated with pneumothorax (lung collapse due to air in the pleural space (space between the ribs and lung pleura where there is physiological negative pressure)).
      • Hereditary leiomyomatosis with renal cell carcinoma – genetic disease with autosomal dominant inheritance; clinical picture: occurrence of multiple cutaneous leiomyomas (benign soft tissue tumors); predominant localization: upper arm, but also the legs, trunk and face may be affected; frequent occurrence also of leiomyomas of the uterus (uterine) and renal cell carcinomas.
      • Hereditary papillary renal cell carcinoma (HPRCC) – genetic disease with autosomal dominant inheritance; results in papillary renal cell carcinomas (basophilic papillary histology, type 1). Mutations in the MET protooncogene have been described on chromosome 7
      • Hippel-Lindau (VHL) syndrome – genetic disorder with autosomal dominant inheritance; patients develop benign angiomas (benign vascular malformations) primarily in the retina (retina) and cerebellum; high risk for clear cell renal cell carcinoma.
      • Tuberous sclerosis (Bourneville-Pringle disease) – genetic disease with autosomal dominant inheritance associated with malformations and tumors of the brain, skin lesions and mostly benign tumors in other organ systems.

Behavioral causes

Disease-related causes

  • Chronic renal failure
  • Hypertension (high blood pressure; elevated systolic blood pressure).
  • Nephrolithiasis (kidney stones) – significantly higher likelihood of papillary renal cell carcinoma than in patients without kidney stones (3.08-fold increased risk); no association with development of clear cell renal carcinoma
  • Terminal renal failure (permanent failure of renal function) (4-fold increased risk).
  • Viral infections
  • Cystic kidney lesions

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

  • Glomerular filtration rate (GFR) ↓ – GFR: < 60 ml/min; mild renal function impairment: 39 percent increase in risk for renal cancer; 129 percent increase in risk for severe impairment.

Medications

  • Aristolochic acids, a group of structurally similar aromatic nitro compounds from Aristolochia species (this genus includes about 400-500 species); component of common Easter lucerne; formerly also the main component of lady’s gold) – Easter lucerne is a putative medicinal plant that often contaminates grain in Balkan regions; The International Agency for Research on Cancer (IARC) classifies aristolochic acid as a carcinogen (cancer-causing).

Environmental pollution – intoxications (poisonings).

  • Arsenic
    • Men: mortality risk (risk of death)/relative risk (RR) 1.75 (95 percent confidence interval 1.49-2.05).
    • Women: Mortality risk/relative risk 2.09 (95-percent confidence interval 1.69-2.57).
  • Heavy metal exposure, especially lead or cadmium are discussed

Other causes

  • Kidney transplantation
  • Dialysis