Biology of Disease

CAUSES OF CANCER

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with anticancer properties. Increased consumption of such vegetables is
inversely related to the incidence of breast and bladder cancers.

A number of nutritional interventions appear to offer some protection
against cancer. These include decreasing the consumption of red meat
and processed red meat, the intake of which is significantly linked
to colorectal cancer. Increasing the consumption of W-3 fats such as
A-linolenic acid, (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA) and decreasing that of W-6 fats such as linoleic acid (Chapter
10 ) is also recommended. Flax seeds, which are a good source both of
dietary fiber and ALA, have been shown to reduce the development of
carcinogen-induced tumors and to reduce the rates of metastasis in
animal models. Numerous studies have indicated that a sufficient vitamin
D (Chapter 10) status offers protection against a variety of cancer types,
and that improvements in its intake by, for example supplementation,
could reduce the incidence of cancer and the associated mortality.
Consumption of selenium, which is present in the active sites of several
enzymes including the antioxidant enzyme glutathione peroxidase
(Chapter 10), has been associated with a decreased risk of prostate
cancer in men. Other studies have suggested that antioxidants, such as
those found in green tea, are protective against cancer, although this is
controversial. In addition a high consumption of lycopene (Figure 17.14),
a carotenoid found in tomatoes, has been shown in several studies to be
associated with a decreased incidence of prostate cancer.

Radiation and Cancer

Ionizing radiation can promote the production of tumors in vivo, and the
transformation of cultured cells in vitro from a normal to a malignant
phenotype. Some of the evidence for radiation-induced carcinogenesis
comes from studies of Japanese people irradiated during the atomic bomb
explosions in Hiroshima (Figure 17.15) and Nagasaki, and from populations
irradiated in nuclear accidents such as that which occurred in Chernobyl
in 1986. Long-term studies of Japanese atom bomb survivors showed an
increase in the incidence of leukemias in the first 5–10 years following
exposure. The risk of solid tumors in these people was also increased
significantly. Studies by Doll (Box 17.2) showed that infants previously
subjected to X-irradiation in utero had an increased risk of developing
leukemias and solid tumors.

The condition xeroderma pigmentosum also provides evidence for
radiation-induced carcinogenesis. These patients suffer multiple skin
cancers caused by the failure of their cells to repair ultraviolet light-induced
damage to DNA. In addition, normal cells in culture may be transformed by
irradiation into cells with a cancerous phenotype. Such studies have been
used to analyze the nature of radiation-induced carcinogenesis.

DNA is also the target of ionizing radiation in radiation-induced carcinogenesis
and the damage caused includes deletions, inversions and translocations
(Chapter 15). Irradiation is also known to induce gene amplification and to
increase chromosomal instability and these, in turn, increase the likelihood of
mutations occurring. Ultimately, mutation events involving proto-oncogenes
and/or tumor suppressor genes are the most likely causes of radiation-
induced carcinogenesis.

With some exceptions, cells are more susceptible to radiation-induced damage
when dividing and this fact has been utilized in the use of radiation to treat
cancer (Section 17.7).

CH 3

H 3 C

H 3 C

H 3 C

H 3 C

H 3 C

CH 3

CH 3

CH 3

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Figure 17.14The structure of lycopene.

Figure 17.15Hiroshima: the Peace Memorial

Park.