Can Our Genes Be Selfish? Hereditary Cancers and Their Genes

Understanding how cancer develops is essential to developing effective treatments. Genetics provides some of the most important contributions in this area.

As we know, cells are the basic building blocks of our bodies. Our cells begin multiplying very rapidly from the moment of conception. In old age, cells multiply only to replace cells that have died.

Cancer at the cellular level is a genetic disease. Mutations (damage) in genes that normally control cell multiplication and communication accumulate with aging and exposure to carcinogens. As mutations accumulate, genes lose their normal functions and cells begin multiplying uncontrollably.

There are 3 types of genes associated with cancer. These are;

Tumor suppressor genes: Prevent uncontrolled cell multiplication.

Oncogenes: Arise when “proto-oncogenes”, normally responsible for cell multiplication, lose their functions. Oncogenes cause cancer to progress aggressively.

DNA repair genes: Are responsible for repairing DNA damage.

Hereditary Cancer Syndromes

As we know, we have a total of 23 chromosome pairs, with one chromosome from the mother and one from the father. Inherited mutations can pass to offspring. In other words, a mutation in genes from either parent can pass to a newborn individual. These individuals have a very high cancer risk.

Hereditary cancers account for approximately % 5-10 of all cancers.

Hereditary Cancer Genes and Syndromes

TP53 (Tumor protein 53): It was selected as the molecule of the century. Known as the guardian of the genome, it functions as a tumor suppressor gene. When a cell's DNA is damaged, it stops cell multiplication, preventing the damage from passing to daughter cells. It also initiates mechanisms to repair DNA. If the damage cannot be repaired, the damaged cell is eliminated through programmed cell death called “apoptosis”.

This is the gene with the most important role in cancer development. In 50 percent of human cancers, p53 is mutated. A mutation in the p53 gene causes Li-Fraumeni syndrome , whose carriers have a very high risk of soft tissue sarcoma, osteosarcoma (bone cancer), breast cancer, brain cancer and blood cancers (leukemia). This syndrome follows dominant inheritance (autosomal dominant). In other words, children born to a mother or father carrying the faulty genes have a 50 percent risk of this syndrome.

Von Hippel-Landau (VHL): The VHL gene is one of the genes that prevent tumor growth. VHL syndrome follows dominant inheritance. People with this syndrome have a very high risk of cancers involving the central nervous system. They also have a high probability of renal cell carcinoma (kidney cancer) and neuroendocrine pancreatic tumors.

MLH: This is one of the genes involved in repairing DNA damage. The hereditary syndrome it causes is HNPCC (hereditary nonpolyposis colon cancer), or Lynch syndrome. It follows dominant inheritance. Lynch syndrome carries a high risk of colon (large bowel), endometrial (uterine), stomach, ovarian and pancreatic cancers.

ERCC: Is involved in DNA repair. Xeroderma Pigmentosum is the syndrome it causes. This syndrome follows recessive inheritance (autosomal recessive). In other words, both genes inherited from the mother and father must be defective. Patients with this syndrome have a 1000-fold higher risk of skin cancer (malignant melanoma) and must avoid sunlight and ultraviolet radiation.

BRCA1 and BRCA2: Are genes involved in DNA repair. Hereditary breast and ovarian cancer syndromesare caused by these genes. Inherited mutations account for 10 percent of breast cancers. The most common inherited mutations in breast cancer occur in BRCA1 and BRCA2. Recent research has also revealed a strong association with prostate cancer.

As genetics has advanced, genetic tests identifying gene defects have entered clinical use. New cancer genes are discovered and the syndromes they cause identified every day. Identifying these genes that cause cancer is very important for developing effective cancer treatments.