Cancer: Biographical Causes and Genetic Factors

Biographical causes/risk factors including genetic factors.

  • Genetic load
    • Cancer (pre)disposition syndrome (cancer disposition/cancer predisposition) in pediatric oncology:
      • ≥ 2 cancers in family members aged less than 18 years, including index patient.
      • Parent or sibling with cancer aged less than 45 years old
      • ≥ 2 first- or second-degree relatives in the same parental line (paternal line) with cancer before age 45.
      • Consanguinity (consanguinity) of the parents.
    • Genetic risk depending on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • SNP: rs2279744 in the MDM2 gene.
          • Allele constellation: GT (affected individuals are more prone to early tumor disease* ).
          • Allele constellation: GG (affected individuals are more prone to early tumor disease* ).
    • Hereditary tumor syndromes with increased risk of malignancy (see below: up to 20% of all cancers are due to inherited mutations).
  • Age – the older the age, the higher the risk of tumor disease, because the genetic repair mechanisms in old age are no longer as effective as in younger years.
  • Hormonal factorsThe number of years in a woman’s life when she is under the influence of estrogens and progestins, especially the years before the first pregnancy carried to term, are of crucial importance for the risk of developing breast carcinoma (breast cancer)!
  • Early first menstrual period (menarche) – so the risk of breast cancer is increased by 50% to 60% for women who had their menarche at age 12 compared to those who had their first menstrual period only at age 16
  • Late first pregnancy – after the age of 30 – circa 3-fold increased risk of breast carcinoma (breast cancer).
  • Short breastfeeding period – the shorter the breastfeeding period, the higher the risk of developing breast cancer. This revealed a meta-study
  • Childlessness – 1.5-2.3-fold increased risk of breast cancer

* Mainly soft tissue sarcoma, diffuse large B-cell lymphoma, colorectal carcinoma (malignant (malignant) tumors of the intestine and rectum), ovarian carcinoma (ovarian cancer), non-small cell bronchial carcinoma (lung cancer) of women, melanoma of women (allele constellation: GG) and a decreased survival rate of patients with gastric and renal cell carcinoma.

Hereditary tumor syndromes with increased risk of malignancy

Hereditary tumor syndromes Gene Frequency* 1 Narrower tumor spectrum
Autosomal-dominant inheritance
Hereditary colorectal cancer without polyposis (HNPCC) MSH2MLH1MSH6PMS2 approx. 1: 500* 2 Colon, endometrial, gastric, small intestinal, urothelial carcinoma, etc.
Familial breast and ovarian cancer BRCA1BRCA2 1: 500 to 1: 1,000 Breast, ovarian and prostate cancer
Neurofibromatosis type 1 NF1 1: 3.000 Neurofibroma, optic glioma, neurofibrosarcoma.
Familial retinoblastoma RB1 1: 15,000 to 1: 20,000 Often bilateral retinoblastoma in childhood, later secondary tumors
Multiple endocrine neoplasia type 2 (MEN2a) RET 1: 30.000 Medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism.
Familial adenomatous polyposis (FAP). APC 1: 33.000 > 100 Colon adenomas, upper gastrointestinal tract tumors, desmoids.
Von Hippel-Lindau disease VHL 1: 36.000 Clear cell renal cell carcinoma and other, mostly benign tumors
Li-Fraumeni syndrome TP53 rare* 3 Particularly broad spectrum of tumors, including sarcomas, breast carcinoma, brain tumors, leukemias
Autosomal recessive inheritance
MUTYH-associated polyposis (MAP) MUTYH no data Colon carcinoma, colon adenomas
Ataxia teleangiectatica ATM 1: 40,000 to 1: 100,000 Non-Hodgkin’s lymphoma, leukemia
Fanconi anemia FANCA-H 1: 100.000 Hematologic neoplasms

* 1 Frequency data refer to the number of plant carriers in the general population. * 2 Approximately 2-3% of all colon carcinomas, estimate of frequency from this.
* 3 Less than 400 families described worldwide. Further notes

  • Sequencing of more than 80 genes that may be involved in carcinogenesis resulted in a high hit rate for pathogenic germline variants (PGV; vulgo cancer genes): at least one pathogenic germline variant (PGV) was found in 397 patients (13.3%):
    • Incidence of each PGV: 7.3% in melanoma (black skin cancer), 20.6% in ovarian cancer (ovarian cancer), 15.9% in pancreatic cancer (pancreatic cancer), 15.3% in colorectal cancer (colon and rectal cancer), 13.7% for prostate carcinoma (cancer of the prostate), 14.7% for bronchial carcinoma (cancer of the lung), 14.5% for cholangiocarcinoma (cancer of the bile duct), 13.3% for endometrial carcinoma (cancer of the uterus or Uterine body cancer) and 14.2% for urinary bladder carcinoma (bladder cancer).
    • Conclusion: the assumption that about 10 to 25% of all cancers are based on inherited mutations, is thus confirmed.