Prevention
is defined as the reduction of cancer mortality via reduction in the incidence of cancer.
This can be accomplished by avoiding a carcinogen or altering its metabolism; pursuing
lifestyle or dietary practices that modify cancer-causing factors or genetic
predispositions; and successfully treating preneoplastic lesions.
Much of the
promise for cancer prevention comes from observational epidemiologic studies that show
associations between modifiable life style factors or environmental exposures and specific
cancers. Evidence is now emerging from randomized controlled trials designed to test
whether interventions suggested by the epidemiologic studies, as well as leads based on
laboratory research, actually result in reduced cancer incidence and mortality.
The most
consistent finding, over what is now decades of research, is the strong association
between tobacco use and cancers of many sites. Hundreds of epidemiologic studies have
confirmed this association. Further support comes from the fact that lung cancer death
rates in the United States have mirrored smoking patterns, with increases in smoking
followed by dramatic increases in lung cancer death rates and, more recently, decreases in
smoking followed by decreases in lung cancer death rates.
Additional
examples of modifiable cancer risk factors include alcohol consumption (associated with
increased risk of oral, esophageal, and other cancers), physical inactivity (associated
with increased risk of colon, breast, and possibly other cancers), and being overweight
(associated with colon, breast, endometrial, and possibly other cancers). Based on
epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption,
being physically active, and maintaining recommended body weight, may all contribute to
reductions in risk of certain cancers. Other lifestyle and environmental factors known to
affect cancer risk (either beneficially or detrimentally) include certain sexual and
reproductive practices, the use of exogenous estrogens, exposure to ionizing radiation and
ultraviolet radiation, certain occupational and chemical exposures, and infectious
agents.
Food and
nutrient intake has been examined in relation to many types of cancer. Fruit and vegetable
consumption has generally been found in epidemiologic studies to be associated with
reduced risk for a number of different cancers. However, it is not currently known which
specific components of fruits and vegetables are responsible for the observed associations
or if they are partially or wholly the result of confounding factors. Contrary to
expectation, randomized trials found no benefit of beta-carotene supplementation in
reducing lung cancer incidence and mortality; in fact, risk of lung cancer was
statistically significantly increased in smokers in the beta-carotene arms of 2 of the
trials. Similarly, randomized controlled trials have found no reduction in risk of
adenomatous polyps of the colon for high-risk individuals taking fiber supplements
compared to those receiving much lower doses of supplemental wheat bran fiber. On the
other hand, there is evidence from at least 1 randomized controlled trial that calcium
supplementation does modestly reduce risk of adenoma recurrence. Consumption of red meat
and inadequate folic acid intake have also been associated with increased risk of colon
cancer. A large randomized trial is currently underway to investigate whether men taking
daily selenium or vitamin E or both experience a reduced incidence of prostate cancer in
comparison to men taking placebo pills.
Daily use of
tamoxifen, a selective estrogen receptor modulator, has been demonstrated to reduce the
risk of developing breast cancer in high risk women by about 50%. Cis-retinoic acid also
has been shown to reduce risk of second primary tumors among patients with primary cancers
of the head and neck. Other examples of drugs that show promise for chemoprevention
include COX-2 inhibitors (which inhibit the cyclooxygenase enzymes involved in the
synthesis of proinflammatory prostaglandins) to reduce the risk of colon cancer and
finasteride (an alpha-reductase inhibitor that reduces testosterone) to lower the risk of
prostate cancer.
Considerable
research effort is now devoted to the development of vaccines to prevent infection by
oncogenic agents, and to potential venues for gene therapy for individuals with genetic
mutations or polymorphisms that put them at high risk of cancer. Meanwhile, genetic
testing for high risk individuals, with enhanced surveillance or prophylactic surgery for
those who test positive, is already available for certain types of cancer, including
breast and colon cancers. Screening for colon cancer through fecal occult blood testing
(FOBT) has been demonstrated to reduce both colon cancer incidence and mortality,
presumably through the detection and removalof precancerous polyps. Similarly, cervical
cytology testing (using the Pap smear) leads to the identification and excision of
precancerous lesions. Over time, such testing has been followed by a dramatic reduction of
cervical cancer incidence and mortality.
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