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* ).
- SNP: rs2279744 in the MDM2 gene.
- Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
- Hereditary tumor syndromes with increased risk of malignancy (see below: up to 20% of all cancers are due to inherited mutations).
- Cancer (pre)disposition syndrome (cancer disposition/cancer predisposition) in pediatric oncology:
- 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.