Role of Genes

Three categories of genes are known to play an important role in the genesis of cancer. These are oncogenes, tumour suppressor genes and mutator genes.

Oncogenes are produced by mutations in the pre-existing normal genes, known as proto-oncogenes. Oncogenes remain harmless in a cell until they are activated by mutations. The activated oncogenes produce aberrant proteins including growth factors and cellular growth factor receptors, which induce unregulated proliferation of the cell leading to genesis of cancer. Peyton Rous of the Rockefeller Institute in New York was the first to discover the existence of oncogenes in 1910, although he got a late recognition for his work. He was awarded the Nobel Prize in Physiology and Medicine in the year 1966, at the age of 85 years. So far, more than thirty oncogenes have been identified, which include: ras family of oncogenes (found in about 50 per cent cases of the human cancer); c-myc oncogene (associated with Burkitt’s lymphoma); N-myc oncogene (associated with neuroblastoma); and HER-2/neu oncogene (associated with the breast and the ovarian cancers). Oncogenes possess tumour specificity, i.e. activation of a particular oncogene causes a specific cancer. There may exist one or two activated oncogenes in a normal cell. Researchers believe that at least three oncogenes must get activated (mutated) in a cell before it becomes malignant.

Tumour suppressor genes, on the other hand, inhibit the genesis of cancer by producing regulatory proteins, which suppress cellular proliferation. If mutation occurs in a tumour suppressor gene, it may lose its tumour suppressing action, leading to unregulated proliferation of the cell. The most important tumour suppressor gene, known so far, is the p53 gene that suppresses uncontrolled proliferation of the cell as well as triggers apoptosis (programmed cell death). The p53 gene is found to be mutated in about 50 per cent cases of the human cancer. Other tumour suppressor genes include: Rb gene (associated with retinoblastoma and osteosarcoma); Ret gene (associated with the endocrine cancer); WT-1 gene (associated with Wilm’s tumour); NF-1 gene (associated with neurofibromatosis type-1); NF-2 gene (associated with neurofibromatosis type-2); APC and DCC genes (associated with the colon cancer). It has been observed that the tumour suppressor genes show a better tumour specificity as compared to the oncogenes.

Mutator genes are another category of genes that have been discovered recently. The job of a mutator gene is to repair the damaged DNA. If mutation occurs in a mutator gene, it may lead to accumulation of the damaged DNA that eventually affects oncogenes and tumour suppressor genes, thus leading to genesis of cancer. Hereditary nonpolyposis colon cancer (HNPCC) is caused by mutations in one of the five mutator genes, known so far.