Genetic Markers and Risk Factors Acting with the
knowledge that approximately 10 percent of breast
cancers run in families, researchers identified muta-
tions in two genes, BRCA1 and 2, as being associated
with such cancers. In 1990, the locus for the BRCA1
gene was found on chromosome 17; BRCA2 was
linked to chromosome 13 four years later, making it
possible to screen for this form of cancer.
In 1994, a marker was likewise identified for a rare
form of thyroid cancer. The RET (rearranged dur-
ing transfection) proto-oncogene, a membrane re-
ceptor for the enzyme tyrosine kinase that functions
to regulate cell division, was found to undergo either
amplification or rearrangement in children with
this disease. In addition, increased risk for colon
cancer was linked to several genetic markers. While
the enzyme telomerase was not encoded by a proto-
oncogene, Dr. Robert Weinberg demonstrated that
its presence and activity may be necessary for cancer
cells to survive.
Certain risk factors or behaviors had been linked
to some cancers for years. In particular, evidence
that changes in the diet from one of high saturated
fat to what has been called the “Mediterranean
diet”—one rich in tomatoes and olive oil—was
linked to reduced risk for colon and prostate cancer.
An American Cancer Society (ACS) guideline re-
leased in 1996 suggested that one-third of cancers
could be prevented with healthier diets. The stron-
gest recommendation involved the link between
smoking and respiratory cancers; the ACS strongly
recommended that use of all forms of tobacco, in-
cluding smokeless (such as snuff), be reduced.
The danger of even secondhand smoke was
recognized during the decade. Studies demon-
strated that a significant risk of lung and other
forms of respiratory cancers was found among
spouses of smokers. In 1993, the Environmental Pro-
tection Agency (EPA) called environmental tobacco
smoke—secondhand smoke—a human carcinogen,
estimating that three thousand persons who are
not themselves smokers die annually from lung can-
cer produced by secondhand smoke. This estimate
did not even address the increased risk of cardiovas-
cular disease. An estimated 150,000-300,000 cases
of respiratory disease such as pneumonia or bron-
chitis in children result from secondhand smoke.
Chemotherapy Several forms of chemotherapy
were approved during the decade. In 1994, Taxol
(paclitaxel) was approved as a treatment for ad-
vanced breast cancer. Additional drugs, tamoxifen
and raloxifene, were also approved for control of
breast cancers. It was reported in 1998 that
tamoxifen had reduced the incidence of breast can-
cer in “high-risk” women by approximately 45 per-
cent, while raloxifene reduced the incidence of
breast cancer in postmenopausal women by 75 per-
cent. Meanwhile, camptostar was approved as a
treatment for advanced colon cancer.
Other treatments utilized new forms of mono-
clonal antibodies, molecules directed at markers
specific to cancer cell surfaces. Herceptin was the
first form of such molecules specific for certain types
of breast cancer. Other types of monoclonal anti-
bodies were approved for use in treating certain lym-
phomas.Impact With the exception of smoking-related can-
cers—lung and respiratory, in particular—the inci-
dence of most forms of cancer either leveled off or
even continued to be reduced during the decade.
These changes could be attributed to several factors.
First was the importance of early screening. The dis-
covery that certain forms of cancer have a congeni-
tal basis—breast cancers, thyroid cancer, albeit a
rare form, and even certain types of colon cancer—
meant that doctors could screen persons at risk. In
addition, improved methods of treatment were de-
veloped and applied during the decade, the object
of which was either to improve the possibility of cure
or at least to prolong life.
In 1990, the surgeon general released a report
emphasizing the benefits of quitting smoking. Ap-
proximately 47 million adults constituted the smok-
ing population—27 percent of men, 23 percent of
women. Given the approximate twenty-year lag be-
tween initiation of smoking and development of
cancer, changes in cancer incidence would not be
observed for decades.
Nevertheless, a reduction in the smoking popula-
tion that originated decades earlier began to dem-
onstrate effects by 1999. While 172,000 cases of re-
spiratory cancer were diagnosed that year, the
incidence in men had declined from 86.5 per
100,000 in 1984 to below 42 per 100,000. The inci-
dence of colon and rectal cancer continued to de-
cline, the result of improved screening and polyp re-
moval. Some 129,400 cases were diagnosed in 1999,
a number that averaged a decline of 1.4 percent forThe Nineties in America Cancer research 149