Certain categories of
agents or factors implicated in carcino-genesis include viruses and bacteria,
physical agents, chemical agents, genetic or familial factors, dietary factors,
and hormonal agents.
Viruses as a cause of
human cancers are hard to determine because viruses are difficult to isolate.
Infectious causes are considered or suspected, however, when specific cancers
appear in clusters. Viruses are thought to incorporate themselves in the
genetic structure of cells, thus altering future generations of that cell
population— perhaps leading to a cancer. For example, the Epstein-Barr virus is
highly suspect as a cause in Burkitt’s lymphoma, nasopharyn-geal cancers, and
some types of non-Hodgkin’s lymphoma and Hodgkin’s disease.
Herpes simplex virus
type II, cytomegalovirus, and human papillomavirus types 16, 18, 31, and 33 are
associated with dys-plasia and cancer of the cervix. The hepatitis B virus is
impli-cated in cancer of the liver; the human T-cell lymphotropic virus may be
a cause of some lymphocytic leukemias and lym-phomas; and the human
immunodeficiency virus (HIV ) is as-sociated with Kaposi’s sarcoma. The
bacterium Helicobacterpylori has been
associated with an increased incidence of gastricmalignancy, perhaps secondary
to inflammation and injury of gastric cells.
associated with carcinogenesis include exposure to sunlight or radiation,
chronic irritation or inflammation, and tobacco use.
Excessive exposure to
the ultraviolet rays of the sun, espe-cially in fair-skinned, blue- or
green-eyed people, increases therisk for skin cancers. Factors such as clothing
styles (sleeveless shirts or shorts), use of sunscreens, occupation,
recreational habits, and environmental variables, including humidity,
alti-tude, and latitude, all play a role in the amount of exposure to
Exposure to ionizing radiation
can occur with repeated diag-nostic x-ray procedures or with radiation therapy
used to treat disease. Fortunately, improved x-ray equipment appropriately
minimizes the risk for extensive radiation exposure. Radiation therapy used in
disease treatment or exposure to radioactive ma-terials at nuclear weapon
manufacturing sites or nuclear power plants is associated with a higher
incidence of leukemias, multi-ple myeloma, and cancers of the lung, bone,
breast, thyroid, and other tissues. Background radiation from the natural decay
processes that produce radon has also been associated with lung cancer. Homes
with high levels of trapped radon should be ven-tilated to allow the gas to
disperse into the atmosphere.
About 75% of all cancers are thought to be related to the envi-ronment.
Tobacco smoke, thought to be the single most lethal chemical carcinogen,
accounts for at least 30% of cancer deaths (Heath & Fontham, 2001). Smoking
is strongly associated with cancers of the lung, head and neck, esophagus,
pancreas, cervix, and bladder. Tobacco may also act synergistically with other
sub-stances, such as alcohol, asbestos, uranium, and viruses, to pro-mote
Chewing tobacco is
associated with cancers of the oral cavity and primarily occurs in men younger
than 40 years of age. Many chemical substances found in the workplace have
proved to be carcinogens or co-carcinogens. The extensive list of suspected
chemical substances continues to grow and includes aromatic amines and aniline
dyes; pesticides and formaldehydes; arsenic, soot, and tars; asbestos; benzene;
betel nut and lime; cadmium; chromium compounds; nickel and zinc ores; wood
dust; beryl-lium compounds; and polyvinyl chloride.
Most hazardous chemicals produce their toxic effects by alter-ing DNA
structure in body sites distant from chemical exposure. The liver, lungs, and
kidneys are the organ systems most often af-fected, presumably because of their
roles in detoxifying chemicals.
Almost every cancer type
has been shown to run in families. This may be due to genetics, shared
environments, cultural or lifestyle factors, or chance alone. Genetic factors
play a role in cancer cell development. Abnormal chromosomal patterns and
cancer have been associated with extra chromosomes, too few chromosomes, or
translocated chromosomes. Specific cancers with underlying genetic
abnormalities include Burkitt’s lymphoma, chronic myelogenous leukemia,
meningiomas, acute leukemias, retinoblas-tomas, Wilms’ tumor, and skin cancers,
including malignant melanoma.
Approximately 5% to 10% of cancers of adulthood and child-hood display a
familial predisposition. Inherited cancer syn-dromes, such as premenopausal
breast cancer, tend to occur at an early age and at multiple sites in one organ
or pair of organs. In cancers with a familial predisposition, individuals may
develop multiple cancers; commonly, two or more first-degree relatives share
the same cancer type. Cancers associated with familial in-heritance include retinoblastomas,
nephroblastomas, pheochro-mocytomas, malignant neurofibromatosis, and breast,
ovarian, endometrial, colorectal, stomach, prostate, and lung cancers. In 1994,
the BRCA-1 gene was identified; it is linked to breast and ovarian cancer syndrome.
The BRCA-2 gene, which has also been identified, is associated with early-onset
breast cancer (Nogueira
• Appling, 2000). Work
continues to identify other specific genes related to cancer incidence (Greco,
Dietary factors are
thought to be related to 35% of all environ-mental cancers (Heath &
Fontham, 2001). Dietary substances can be proactive (protective), carcinogenic,
or co-carcinogenic. The risk for cancer increases with long-term ingestion of
car-cinogens or co-carcinogens or chronic absence of proactive sub-stances in
associated with an increased cancer risk include fats, alcohol, salt-cured or
smoked meats, foods contain-ing nitrates and nitrites, and a high caloric
dietary intake. Food substances that appear to reduce cancer risk include
high-fiber foods, cruciferous vegetables (cabbage, broccoli, cauliflower,
Brus-sels sprouts, kohlrabi), carotenoids (carrots, tomatoes, spinach,
apricots, peaches, dark-green and deep-yellow vegetables), and pos-sibly
vitamins E and C, zinc, and selenium.
Obesity is associated with endometrial cancer and possibly
postmenopausal breast cancers. Obesity may also increase the risk for cancers
of the colon, kidney, and gallbladder.
Tumor growth may be promoted by disturbances in hormonal balance either
by the body’s own (endogenous) hormone pro-duction or by administration of
exogenous hormones. Cancers of the breast, prostate, and uterus are thought to
depend on en-dogenous hormonal levels for growth. Diethylstilbestrol (DES) has
long been recognized as a cause of vaginal carcinomas. Oral contraceptives and
prolonged estrogen replacement therapy are associated with increased incidence
of hepatocellular, endome-trial, and breast cancers, whereas they appear to
decrease the risk for ovarian and endometrial cancers. The combination of
estro-gen and progesterone appears safest in decreasing the risk for
en-dometrial cancers. Hormonal changes with reproduction are also associated
with cancer incidence. Increased numbers of pregnan-cies are associated with a
decreased incidence of breast, endometrial, and ovarian cancers.