Cancer formation begins when DNA in a cell or population of cells is harmed after exposure to carcinogens. These cancer-producing toxins can come from the person’s environment or be a product of regular bodily processes. For example, long-term exposure to viral or bacterial infection may cause chronic inflammation that hurts cells and DNA. Ultraviolet and gamma radiation can also injure DNA. Or a person’s normal oxidative metabolism can generate reactive oxygen species (ROS) carcinogens, which in turn can attack DNA.
Many exogenous (from outside the body) carcinogens need to be activated by metabolic enzymes, but detoxification enzymes such as the glutathione S-transferases also exist to deactivate carcinogens or their intermediate metabolites. People who have inherited genetic variations known as polymorphisms in these types of enzymes may have altered rates of enzyme activation or detoxification, thus increasing or decreasing the carcinogenic potential of environmental exposures. In other words, they will have advantages or disadvantages when it comes to how their bodies deal with carcinogens. Carcinogens can also induce cancer by affecting epigenetic changes, such as DNA methylation, which alter a gene’s activity without changing the underlying DNA sequence. Once the cancer process has begun, either the cell’s defense mechanism detects the abnormality and targets the cell for destruction or the accumulation of further genetic defects helps the flawed cell escape these defenses. The defects may also give these mutated cells a growth advantage, so that they multiply and spread from the site of origin to other sites in the body. In essence, cancer develops from the build-up of DNA damage and changes over several years and from many causes. This explains why aging is a major risk factor associated with most cancers. Less than 0.1 percent of the total number of cancer cases occurs in people younger than 15, whereas nearly 80 percent of cancer cases are found in people age 60 or older.
Several factors inside the body and in the environment play a role in the development of cancer. Environmental exposure to a variety of natural and manufactured substances makes up at least two-thirds of all cancer cases. These include lifestyle choices such as smoking tobacco, overindulging in alcohol, poor diet, lack of exercise, excessive sunlight exposure, risky sexual behavior, and increased exposure to some viruses. Other causes may include exposure to certain drugs, hormones, radiation, viruses, bacteria, and environmental chemicals present in the air, water, or workplace. Most chemicals are not carcinogenic, but a wide variety of chemicals can promote the disease. And so cancer is a multifaceted genetic disease that often requires multiple genetic lesions to breach the body’s safeguards. Even people who have inherited flaws in critical protective genes usually do not develop cancer for many years. Yet in many if not most humans the massive accumulation of mutations during a lifetime ensures that some form of malignant disease will eventually develop.