A normal, healthy body detects and removes cancerous cells before they spread and cause disease. Mutations in genes that control normal cancer surveillance or that allow abnormal cells to evade it can increase a person's risk for developing cancer. Gene mutations that increase the risk for developing lung cancer can be inherited from the parents, as a germline mutation, or can be acquired later as cells copy themselves and divide, as a somatic mutation. Some somatic mutations that cause lung cancer occur in response to an environmental toxin, such as cigarette smoke.
EGFR
According to the Mayo Clinic, lung cancers fall into two broad categories: small cell cancers, which are less common and almost always occur in smokers, and non-small cell cancers, which can affect smokers and non-smokers. Online Mendelian Inheritance in Man, or OMIM, presents information on the role of the gene EGFR in predisposition to lung cancer. EGFR, the epidermal growth factor receptor gene on the short arm of chromosome 7, encodes a protein that has critical roles in cell proliferation and survival. When EGFR malfunctions, cancer cells can survive and spread. People with a mutation in EGFR might be more susceptible to non-small cell lung cancer -- mainly the type called adenocarcinomas. Two particular mutations in EGFR occur most often in people who never smoked, and confer a good response to a cancer drug called gefitinib that usually does not help adenocarcinomas.
p53
OMIM reports that all types of lung cancer frequently show mutations in p53, a gene on chromosome 17 that normally acts as a cancer preventer. It regulates a network of other genes that monitor cell division to prevent out-of-control growth, repair damaged DNA, and help cells commit suicide when they are old or damaged. Mutations in p53 allow cells to grow out of control and without regard to the welfare of other nearby cells; in other words, cells lacking p53 become cancerous. Most p53 mutations are acquired, not inherited, and it usually takes two mutated copies of p53 to cause cancer. People who inherit a p53 mutation and expose themselves to a high risk of p53 mutation from the carcinogens in cigarette smoke have over three times the risk of getting lung cancer compared to non-smokers who inherit a p53 mutation.
Other Genes
Many other gene mutations can increase a person's risk for developing lung cancer. In addition to p53 and EGFR, OMIM lists 19 other gene mutations that commonly occur in lung cancer. Some mutations alter the sequences of bases in the genetic code, some remove a part of a gene and some duplicate parts of a gene. Others are common variants also found in healthy people, but that increase the risk of eventually developing cancer, especially in smokers.
Smoking and Genetics
Tobacco smoke contains a number of chemicals that are carcinogens, or cancer-causing agents. Over time, the carcinogens damage cells and cause gene mutations beyond the body's ability to repair them. Lung cancer occurs when the damage happens to turn off a gene that prevents cancer, or turn on a gene that promotes cancer.
