A
huge international effort involving more than 100 institutions and
genetic tests on 200,000 people has uncovered dozens of signposts in DNA
that can help reveal further a person's risk for breast, ovarian or
prostate cancer, scientists reported Wednesday.
It's the latest
mega-collaboration to learn more about the intricate mechanisms that
lead to cancer. And while the headway seems significant in many ways,
the potential payoff for ordinary people is mostly this: Someday there
may be genetic tests that help identify women with the most to gain from
mammograms, and men who could benefit most from PSA tests and prostate
biopsies.
And perhaps farther in the future these genetic clues might lead to new treatments.
"This
adds another piece to the puzzle," said Harpal Kumar, chief executive
of Cancer Research U.K., the charity which funded much of the research.
One
analysis suggests that among men whose family history gives them
roughly a 20 percent lifetime risk for prostate cancer, such genetic
markers could identify those whose real risk is 60 percent.
The
markers also could make a difference for women with BRCA gene mutations,
which puts them at high risk for breast cancer. Researchers may be able
to separate those whose lifetime risk exceeds 80 percent from women
whose risk is about 20 to 50 percent. One doctor said that might mean
some women would choose to monitor for cancer rather than taking the
drastic step of having healthy breasts removed.
Scientists have
found risk markers for the three diseases before, but the new trove
doubles the known list, said one author, Douglas Easton of Cambridge
University. The discoveries also reveal clues about the biological
underpinnings of these cancers, which may pay off someday in better
therapies, he said.
Experts not connected with the work said it
was encouraging but that more research is needed to see how useful it
would be for guiding patient care. One suggested that using a gene test
along with PSA testing and other factors might help determine which men
have enough risk of a life-threatening prostate cancer that they should
get a biopsy. Many prostate cancers found early are slow-growing and
won't be fatal, but there is no way to differentiate and many men have
surgery they may not need.
Easton said the prospects for a genetic test are greater for prostate and breast cancer than ovarian cancer.
Breast
cancer is the most common malignancy among women worldwide, with more
than 1 million new cases a year. Prostate cancer is the second most
common cancer in men after lung cancer, with about 900,000 new cases
every year. Ovarian cancer accounts for about 4 percent of all cancers
diagnosed in women, causing about 225,000 cases worldwide.
The new
results were released in 13 reports in Nature Genetics, PLOS Genetics
and other journals. They come from a collaboration involving more than
130 institutions in the United States, Europe, and elsewhere. The
research was mainly paid for by Cancer Research U.K., the European Union
and the U.S. National Institutes of Health.
Scientists used scans
of DNA from more than 200,000 people to seek the markers, tiny
variations in the 3 billion "letters" of the DNA code that are
associated with disease risk.
The scientists found 49 new risk
markers for breast cancer plus a couple of others that modify breast
cancer risk from rare mutated genes, 26 for prostate cancer and eight
for ovarian cancer.
Individually, each marker has only a slight
impact on risk estimation, too small to be useful on its own, Easton
said. They would be combined and added to previously known markers to
help reveal a person's risk, he said.
A genetic test could be
useful in identifying people who should get mammography or PSA testing,
said Hilary Burton, director of the PHG Foundation, a genomics
think-tank in Cambridge, England. A mathematical analysis done by her
group found that under certain assumptions, a gene test using all known
markers could reduce the number of mammograms and PSA tests by around 20
percent, with only a small cost in cancer cases missed.
Among the new findings:
-
For breast cancer, researchers calculated that by using all known
markers, including the new ones, they could identify 5 percent of the
female population with twice the average risk of disease, and 1 percent
with a three-fold risk. The average lifetime risk of getting breast
cancer is about 12 percent in developed countries. It's lower in the
developing world where other diseases are a bigger problem.
- For
prostate cancer, using all the known markers could identify 1 percent of
men with nearly five times the average risk, the researchers computed.
In developed countries, a man's average lifetime risk for the disease is
about 14 to 16 percent, lower in developing nations.
-Markers can
also make a difference in estimates of breast cancer risk for women
with the BRCA1 or BRCA2 gene mutations. Such women are rare, but their
lifetime risk can run as high as 85 percent. Researchers said that with
the new biomarkers, it might be possible to identify the small group of
these women with a risk of 28 percent or less.
For patients like
Vicki Gilbert of England, who carries a variation of the BRCA1 gene,
having such details about her cancer risk would have made
decision-making easier.
Gilbert, 50, found out about her genetic
risk after being diagnosed with the disease in 2009. Though doctors said
the gene wouldn't change the kind of chemotherapy she got, they
suggested removing her ovaries to avoid ovarian cancer, which is also
made more likely by a mutated BRCA1.
"They didn't want to express a
definite opinion on whether I should have my ovaries removed so I had
to weigh up my options for myself," said Gilbert, a veterinary
receptionist in Wiltshire. "...I decided to have my ovaries removed
because that takes away the fear it could happen. It certainly would
have been nice to have more information to know that was the right
choice."
Gilbert said knowing more about the genetic risks of
cancer should be reassuring for most patients. "There are so many
decisions made for you when you go through cancer treatment that being
able to decide something yourself is very important," she said.
Dr.
Charis Eng, chair of the Genomic Medicine Institute at the Cleveland
Clinic, who didn't participate in the new work, called the breast cancer
research exciting but not ready for routine use.
Most women who
carry a BRCA gene choose intensive surveillance with both mammograms and
MRI and some choose to have their breasts removed to prevent the
disease, she said. Even the lower risk described by the new research is
worrisomely high, and might not persuade a woman to avoid such
precautions completely, Eng said
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