Info

Estimated

Estimated

Type of Cancer

New Cases per Year

Deaths per Year

Prostate

189,000

30,200

Breast

205,000

40,000

Lung and bronchus

169,400

154,900

Colon and rectum

148,300

56,600

Lymphoma

60,900

25,800

Bladder

56,500

12,600

Melanoma

53,600

7,400

Uterus

39,300

6,600

Leukemias

30,800

21,700

Oral cavity and pharynx

28,900

7,400

Pancreas

30,300

29,700

Ovary

23,300

13,900

Stomach

21,600

12,400

Brain and nervous system

17,000

13,100

Liver

16,600

14,100

Uterine cervix

13,000

4,100

Cancers of soft tissues including heart

8,300

3,900

All cancers

1,268,000

553,400

Source: American Cancer Society, Cancer Facts and Figures, 2002 (Atlanta: American Cancer Society, 2001), p. 80

Source: American Cancer Society, Cancer Facts and Figures, 2002 (Atlanta: American Cancer Society, 2001), p. 80

Early observations suggested that cancer might result from genetic damage. First, it was recognized that many agents such as ionizing radiation and chemicals that cause mutations also cause cancer (are carcinogens). Second, some cancers are consistently associated with particular chromosome abnormalities. About 90% of people with chronic myeloid leukemia, for example, have a reciprocal translocation between chromosome 22 and chromosome 9 (see Figure 9.34). Third, some specific types of cancers tend to run in families. Retinoblastoma, a rare childhood cancer of the retina, appears with high frequency in a few families and is inherited as an autosomal dominant trait, suggesting that a single gene is responsible for these cases of the disease.

Although these observations hinted that genes play some role in cancer, the theory of cancer as a genetic disease had several significant problems. If cancer is inherited, every cell in the body should receive the cancer-causing gene, and therefore every cell should become cancerous. In those types of cancer that run in families, however, tumors typically appear only in certain tissues and often only when the person reaches an advanced age. Finally, many cancers do not run in families at all and, even in regard to those cancers that generally do, isolated cases crop up in families with no history of the disease.

In 1971, Alfred Knudson proposed a model to explain the genetic basis of cancer. Knudson was studying retinoblastoma, a cancer that usually develops in only one eye but occasionally appears in both. Knudson found that, when retinoblastoma appears in both eyes, onset is at an early age, and affected children often have close relatives who also have retinoblastoma.

Knudson proposed that retinoblastoma results from two separate genetic defects, both of which are necessary for cancer to develop (IFigure 21.22). He suggested that, in the cases in which the disease affects just one eye, a single cell in one eye undergoes two successive mutations. Because the chance of these two mutations occurring in a single cell is remote, retinoblastoma is rare and typically develops in only one eye. For bilateral cases, Knudson proposed that the child inherited one of the two mutations required for the cancer, and so every cell contains this initial mutation. In these cases, all that is required for cancer to develop is for one eye cell to undergo the second mutation. Because each eye possesses millions of cells, there is a high probability that the second mutation will occur in at least one cell of each eye, producing tumors in both eyes at an early age.

Knudson's hypothesis suggests that cancer is the result of a multistep process that requires several mutations. If one or more of the required mutations is inherited, fewer

^ Rarely7a~singie~cei^B^B^^^resulting in a single

undergoes two somatic mutations,.

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