Cancer Causes and Risk Factors

Cancer is caused by gain-of-function mutations in proto-oncogenes or loss-of-function mutations in tumor suppressor genes.

Cancer has many causes, but at its most basic level, cancer is caused by genetic mutations. Although many different mutations can lead to cancer, they can generally be classified into two groups: mutations that result in a gain of function and mutations that result in a loss of function.

A gene variant that results from a mutation is known as an oncogene. An oncogene is a gene that can cause cancer if it undergoes certain mutations. The corresponding normal version of the oncogene without the mutation is called a proto-oncogene. Only a single copy of an oncogene needs to be mutated in order for cancer to form. This makes oncogenes especially dangerous.

Proto-Oncogene Transformation

Proto-oncogenes are known to cause normal cells to transform into cancer cells when they are mutated. If a proto-oncogene is mutated, it is called an oncogene. When an oncogene is expressed, it increases the production of proteins that cause cells to rapidly divide.
A loss-of-function mutation requires that both copies of the gene be mutated in order for cancer to occur. Thus, the normal version of a loss-of-function gene that leads to cancer is known as a tumor suppressor gene. Mutations in tumor suppressor genes lead to cancer less frequently than mutations in proto-oncogenes because both copies of the gene must undergo the same mutation. However, epigenetic changes, or heritable changes in the expression of genes, can lead to the inactivation of tumor suppressor genes without mutations to the genes, resulting in cancer. Although the genetic causes of cancer are many and varied, they tend to affect a limited number of regulatory pathways. The most common pathways affected are those involved in cell growth, response to DNA damage, and cell proliferation.

Regulatory Pathways that Lead to Cancer

Many different genes can cause cancer, yet they usually affect one of three regulatory pathways: those involved in cell growth, cell proliferation, and the response to changes in DNA.
Many factors have been shown to increase the risk of developing cancer. For example, cervical cancer is associated with an infection from the human papilloma virus (HPV). Smoking tobacco is known to cause lung cancer, and smokeless tobacco can do the same for the tissues of the mouth. Sun exposure can lead to skin cancer. Also, there is the possibility of being exposed to certain chemicals or substances called carcinogens, which are known to cause cancer. A carcinogen is a substance that causes cancer. For example, asbestos, a material that was once common in home insulation, is a carcinogen. Carcinogens are ranked according to the likelihood they will cause cancer.

However, not all cancers arise from environmental stimuli. Some cancers are encoded in a person's genes from birth. For example, when multiple cancers such as breast and ovarian cancer are present in the same individual, often the cancers are caused by inherited mutations. Cancers that arise from inherited mutations are present in the germ cells of the person and can be passed to offspring. A germ cell is a reproductive cell, such as a sperm or an egg. Genetic testing and counseling can help people with a family history of these types of cancers determine how best to approach treatment and family planning.

Despite the existence of heritable cancer mutations, most mutations arise from environmental influences.Typically, several mutations combine to cause cancer. A common tumor suppressor gene is p53, which helps regulate the cell cycle. Mutations in p53 exist in over half of all cancers. However, other mutations are usually also present, such as BRCA1 and BRCA2, which lead to breast cancer.