Is cancer a contagious disease?

From: JWissmille (jwissmille_at_aol.com)
Date: 07/31/04 

Date: 31 Jul 2004 04:04:45 GMT

Business Week, 07.14.1997

 no... ...but research reveals new
links between everyday bugs and life-threatening diseases

In late June, a report in The New England Journal of Medicine roused
infections-disease experts around the world. It described how a
12-year nationwide vaccination program against rampant hepatitis B in
Taiwan brought a decrease in cases of childhood liver cancer.

It was a remarkable development: An effort to combat an infectious
disease had also proven effective against cancer. Cancer and
contagion. That's a terrifying association-one that most doctors are
loath to make. It's also misleading by any conventional definition of
contagion.

Nonetheless, a growing and highly respected community of researchers
in cancer and infectious diseases believes that
microorganisms-viruses, bacteria, and parasites-play a
significant role in cancer, heart disease, diabetes, and other
illnesses that are not traditionally regarded as infectious. In
essence, the bugs are "cofactors." In that regard, the Taiwan study
"is very significant," says Dr. Anthony S. Fauci, head of the National
Institute of Allergy and Infectious Diseases.

Early hints

The idea is not new. A hundred years ago, doctors noted a connection
between cervical cancer and sexual promiscuity that transcended mere
coincidence. By the 1960s, a connection between microbes and animal
cancers had become well established, but scientists failed to
demonstrate the same association in humans. Even today, some
researchers resist the notion of infectious cofactors because in the
case of cancer-hundreds of millions of people worldwide carry the
suspect agents, yet don't get sick. Nevertheless, scientists armed
with exceedingly powerful research tools are drawing new microbial
connections to noninfectious diseases at a faster rate than ever
before. For the first time, it is possible to make absolute
associations between some microbes and cancer, says Fauci.

The link between hepatitis B and liver cancer, he says, is a "slam
dunk." The same is true of human papillomavirus (HPV) and cervical
cancer. Researchers have drawn weaker but no less tantalizing
connections between Helicobacter pylori-the bacterium that causes
ulcers-and two types of stomach cancer. The common parasite Chlamydia
pneumoniae could be associated with cardiovascular diseases. In Japan,
a retrovirus called HTLV-1 has long been linked with leukemia.
Epstein-Barr virus (EBV) is associated with a common lymphoma in
Africa. And Kaposi's sarcoma herpes virus (KSHV), discovered in 1993
by Patrick Moore and Yuan Chang at Columbia University, appears to be
the cause of Kaposi's sarcoma, a cancer that is a scourge of AIDS
patients.

Last month, an article in Science further linked KSHV with a more
common cancer of the
blood called multiple myeloma (table).None of these associations is
simple or transparent. In this sense, cancer and heart disease have
little in common with classic plagues or pests.
Malaria, polio, cholera, bubonic plague, and virulent staphylococcus
infections are all caused by well-known parasites, viruses, or
bacteria. And the pathways the microbes use to wreak their
devastations are well understood. In contrast, with complex illnesses
such as cancer, heart disease, and diabetes, infection seems to cause
problems only when combined with a suppressed immune system, the
presence of a chemical agent, or a genetic predisposition. In most
cases "we don't know what these other factors are," says Harvard
Medical School Professor Martin S. Hirsch. "But those of us in the
field think most diseases could turn out to have infectious cofactors.
 "Not all scientists agree-particularly when it comes to
mainstreamcancers.

Robert A. Weinberg, a member of the Whitehead Institute for Biomedical
Research in Cambridge, Mass., says such theories were well explored in
the 1960s and '70s. And with a few important exceptions-HPV, hepatitis
B, EBV, and Kaposi's sarcoma virus-they simply did not pan out. In
America, Weinberg says, the cancers linked with these bugs make up
just a few percent of all cancer cases. He believes most human cancers
ultimately will be traced to the actions of certain cancer-causing
genes, not to infectious organisms. It's true that few virologists
actively hunt for microbial causes of breast or prostate
cancer. But if the scope ofinquiry is widened to include less
developed countries, the scale of microbial involvement is not
trivial. The International Agency for Research on Cancer, an arm of
the World Health Organization, believes microbe-linked cancers-mainly
cervical and liver-make up 20% of all cancers in the Third World. And
even in the U. S., the failure to find microbial cofactors in major
diseases may lie with the researchers. Not all cancer-associated
viruses reside in the tumor cell, says James Berenson, professor of
medicine at the University of California at Los Angeles and co-author
of the recent Science article on Kaposi's sarcoma herpes
virus.Berenson says this microbe is associated with 100% of multiple
myeloma cases. But it's notin the cancer cells. It's in a type of
immune cell in the bone marrow called a dendritic cell.

Double whammy

That makes the virus doubly insidious, he says. Once the virus is
inside the dendritic cell,
Berenson believes, it "down-regulates" a part of the cell that
presents foreign antigens to the immune system. In effect, it becomes
invisible to other immune cells and can't be attacked. "So not only
does the virus drive the tumor," Berenson speculates, "it also messes
up the immune system. "Researchers say cancer-linked microbial
infections fall
into two camps. On one side are viruses that trigger cancer by
switching off human genes
that suppress tumors "Such viruses cause the cell to lose normal
growth control," says Walter Eckhart, director of the Salk Institute's
Cancer Center in La Jolla, Calif. For example, HPV makes proteins that
interfere with two tumor-suppressor genes, the p-53 gene and the
retinoblastoma gene, according to Howard D. Strickler, a National
Cancer Institute researcher. In the other camp are microbes that
cause irritation and can trigger cancer when the body's response goes
astray. In the case of Helicobacter pylori, for example, stomach cells
mutate to avoid damage from the bacterium, says Julie Parsonnet,
associate professor of medicine at Stanford University. The mutation
can lead to cancer. Similarly chronicirritation from schistosomiasis,
a parasitic killer in Africa, Asia, and Latin America, may cause
bladder cancer. And a flatworm called the liver fluke may cause liver
and biliary cancers.

In this camp, H. pylori is among the most pernicious microbes. But its
role in cancer remains controversial. That galls Peter G. Isaacson,
head of histopathology at
University College London Medical School, who says that at least one
type of malignant
lymphoma under investigation "arises in the stomach in the setting of
H. pylori inflammation, and only there." Why do others doubt it? In
part because the bug infects millions of people, while only a few get
cancer. But therapeutic results should dispel their doubts, Isaacson
argues. In 70% of H. pylori-infected patients who have the lymphoma,
treatment with appropriate antibiotics leads to regression, he claims.
Multiple sclerosis and diabetes may also be fertile ground for finding
infectious cofactors. "A wide variety of microbial agents can cause
diseases such as diabetes when they are injected in animals," notes
Michael Oldstone, a professor of virology and immunology at Scripps
Research Institute in La Jolla, Calif. There are hints of similar
pathology in humans. Says Alvin Friedman-Kien, professor of
dermatology and microbiology at New York University Medical Center:
"There are many new agents waiting to be discovered."

Rethinking the microbial basis of such illnesses has huge implications
for public health and for disease treatment, and prevention. Consider
heart disease, the No. 1 killer worldwide. For years, researchers have
noted the presence of Chlamydia pneumoniae in arteries of heart
patients and in the plaques that cause clogging. Now, doctors are
looking at the infection as a therapeutic target. In a two-year trial
at St. George's Hospital in London, cardiologist Sandeep Gupta gave
antibiotics to 40 people with high levels of antibodies to Chlamydia
while administering a placebo to 40 others. He believed the high
antibody presence might signal a chronic infection. And he hoped that
attacking it with an
antibiotic would reduce the key "markers" in the blood, such as,
inflammatory markers and clotting agents. The results: The drugs led
to reduced levels of Chlamydia antibodies and the markers. What's
more, says Gupta, recipients of the drugs suffered fewer subsequent
heart attacks. If larger studies bear this out, "it will open a whole
new area for the treatment of heart attacks by antibiotics," he says.
That could be especially useful in the Third World, "because
traditional treatments like angioplasty are so expensive."

Research into microbe-linked cancers could provide a much needed boost
to disease
screening. A precancerous condition called cervical dysplasia strikes
600,000 to 1 million
American women each year, notes John Curtin, associate attending
surgeonat Memorial
Sloan Kettering Cancer Center in New York. "You can already use human
papillomavirus as a discriminator between high-risk and low-risk
groups," he argues. Disease-causing bugs may be vulnerable to
vaccination programs, on the model of Taiwan's battle with hepatitis
B.

Drug makers are now scrambling to develop vaccines against HPV and
other
cancer-linked viruses. MedImmune Inc. in Gaithersburg, Md., has begun
clinical trials
for an HPV vaccine. Likewise, biotech startup Cantab Pharmaceuticals
Research Ltd. in
Cambridge, England, is doing preclinical work on three different
therapeutic vaccines to attack genital warts and cervical cancer.
Cantab sees the possibility for 2.5 million patients
worldwide, with yearly sales as high as $490 million. "Basically,
everyone who has sex is at risk," says Joel M. Palefsky, associate
professor of laboratory medicine at the University
of California at San Francisco.

While success stories are still rare, the idea of treating
precancerous conditions with antiviral drugs is gaining currency. Dr.
Susan Krown, a Kaposi's sarcoma specialist at
Sloan-Kettering, cites anecdotal evidence that the use of antiherpes
drugs could thwart
tumors in patients who carry the Kaposi's sarcoma virus but haven't
developed cancer. In the hunt for microbial cofactors, researchers are
faced with many perplexing issues. Why do common infections, on rare
occasions, produce tragic outcomes? What therapeutic advances can
researchers hope for in microbe-linked cancer, when viruses such as
herpes and HPV are almost impossible to cure? "Antiviral therapy is
still in an infant stage compared with antibacterial work," says NYU's
Friedman-Kien.

Despite these hurdles, most researchers are optimistic. In the
developing world, where
pathogens may play a larger role in certain widespread cancers,
prevention programs that
target infectious diseases could have a huge impact. So could
continuing research on
pathogens involved in such unilluminated ills as diabetes and multiple
sclerosis. Researchers can count on accelerated discovery. In rapid
succession, scientists have
identified eight distinct herpes viruses and linked all but one with
specific ills. More than 70 types of human papillomaviruses have been
found. Not all have even been named. "This is an extraordinary time,"
says the NCI's Strickler. As scientists analyze the link between
microbes and disease, they're bound to find new ways to intervene.

By Neil Gross, with Naomi Freundlich in New York and Heidi Dawley in
London

A plausible leap from bacteria to cancer

1 The bacterium called Helicobacter pylori may be passed from unwashed
hands to mouths in day-care centers. Some scientists say flies may
deposit bacteria on
food.

2 H. pylori is found in stomachs of a quarter of all U.S. adults.
Third world infection rates are higher.

3 The bacterium causes inflammation of the mucous membrane of the
stomach, called
gastritis.

4 Gastritis may develop into ulcers. About 20% of people infected with
H. pylori get
stomach ulcers.

5 Gastritis can also develop into stomach cancer. Some 50% of such
cancers may be linked with H. pylori.

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