21 March 2005

Lecture 27

Reading: Chapter 6, Chapter 8

D. Mutations

See pages 144, 206, and 548 in your text for information specific to cancer.

c. Inherited tendencies toward cancer

Typically, tumors do not start until several mutations in oncogenes and tumor suppressor genes have accumulated in the cells that form tumors. For example, the most common type of colon cancer results from four mutations, one in an oncogene, two in tumor suppressors, and a fourth that is less understood. Such mutations accumulate over a lifetime, which is why cancer is more common in older people than younger. In some cases, such mutations are inherited and predispose the individual to cancer, since fewer mutations need to accumulate for inappropriate cell division to occur.

An inherited mutation in the BRCA 1 gene predisposes to breast cancer. In the general population, 10% of American women eventually suffer from breast cancer. Among women with the inherited BRCA 1 mutation (or a mutation in a related gene called BRCA 2) the incidence is 80%. BRCA 1 codes for a DNA repair protein that repairs DNA damage and prevents mutations. Loss of BRCA 1 activity by the mutation causes the group of mutations that trigger breast cancer to occur more readily and earlier in life. BRCA 1 mutations also predispose to ovarian, prostate, and colon cancer.

The BRCA 1 and 2 mutations are most common among descendants of Jewish families from central Europe (the Ashkenazi). Among these people, the incidence of BRCA 1 or 2 mutations may be as high as 5 percent. In the US population as a whole, the BRCA 1 and 2 mutations have an incidence estimated at 0.2%.

A variety of inherited mutations that predispose to cancer are known and more are being searched for in the human genome. Genetic testing can identify whether you carry such mutations.

 d. "Causes" of cancer

A variety of factors can cause the mutations that can accumulate and trigger cancer.

Ultraviolet and ionizing radiation from sunlight or radioactive elements, respectively can cause DNA damage and thus the mutations that trigger cancer. Ultraviolet light from the sun triggers skin cancers, since it does not penetrate your body very deeply. Tanning lamps also cause skin cancer by exposing you to ultraviolet radiation. Ionizing radiation, e.g. X-rays, passes through you fairly easily and can trigger cancers throughout your body.

Chemical carcinogens are chemicals that cause DNA damage. Some potent chemical carcinogens include compounds in cigarette smoke and certain asbestos fibers.

Viruses that integrate with the host cell DNA may also cause mutations when they do so. Infection with the human papilloma virus (HPV) has been associated with cervical cancer in several studies.

Diet has been proposed as a factor for some types of cancers. High intake of partially hydrogenated vegetable oils has been linked to colon cancer in animal studies. Recent human studies have not strongly supported this finding, however.

Hormones, e.g. estrogen and testosterone, may favor cancers because they increase cell division in some tissues. Mutations can occur any time a cell divides. Growth of tumors may also be stimulated by these hormones.

e. Treatments for cancer

Traditional treatments for cancer include surgery to remove tumors and/or radiation or chemotherapies that stop cell division of remaining tumor cells. The latter often stop cell division in non-tumor cells also, which is one reason they have unpleasant side effects. Treatments that specfically kill cancer cells but ignore normal cells are being developed. These employ drugs that more specifically recognize tumor cells or manipulate the immune system so that it attacks tumor cells more aggressively.