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News
Gene Mutations Boost Cancer Risk in Women
24 October 2003
By PAUL RECER
WASHINGTON - Exercising and maintaining a healthful weight when young
can delay the onset of breast cancer in women at very high risk of the
disease, according to a study of women with a genetic mutation that gives
them an 82 percent lifetime risk of developing the disease.
Researchers also found that women with mutations in the BRCA1 or BRCA2
gene have a 23 percent to 54 percent risk of ovarian cancer, depending on
which gene is affected.
The study, appearing Friday in the journal Science, showed that lifestyle
during adolescence played a role in when these high-risk women developed
breast cancer. The finding was consistent with earlier studies suggesting
that among women in general, exercise and healthy weight early in life can
reduce a woman's risk of developing breast cancer after menopause.
"The possibility that lifestyle changes such as increased exercise and
weight control could modify the impact of genetic risk has very intriguing
implications, not only for BRCA-related cancers but for other breast
cancers as well," said Dr. Larry Norton, head of the division of solid
tumor oncology at Memorial Sloan-Kettering Cancer Center.
In the new study, women who exercised actively when they were young -
either dancing, or in team sports, or just walking a lot - and who
maintained a healthful weight - that is, they were not obese - through the
age of 21, were somewhat protected from breast cancer, said Mary-Claire
King, first author of the study and a professor of genome sciences at the
University of Washington, Seattle.
"If they carried the mutation, they still had a very high risk, but their
age of diagnosis was pushed to later in life," she said.
Earlier studies had suggested that women with the gene mutations have a
risk ranging from 25 percent to 80 percent of developing breast cancer in
their lives. The new study estimates the risk at 82 percent.
For ovarian cancer, which has also been linked to the gene mutations, the
study found the lifetime risk was 54 percent for BRCA1 and 23 percent for
BRCA2 mutations. This compares with a risk for the general population of
about 1.8 percent.
Researchers analyzed genes from 1,008 Ashkenazi Jewish women who had
breast cancer and found that 104 of the patients had a mutation in the
BRCA1 or BRCA2 gene. Half of the women had no immediate female relatives
with breast or ovarian cancer, suggesting most of those women inherited the
mutated gene from their fathers, the researchers said.
The researchers then analyzed the BRCA genes for 2,000 people in the
families of the breast cancer patients.
Based on the findings, the scientist estimated that women with one of the
mutations has a:
- 20 percent chance of developing breast cancer by age 40.
- 55 percent chance by age 60.
- 82 percent risk by the age of 80.
For women in general, the risk of breast cancer over a lifetime is about
10 percent. Among breast cancer patients generally, only 5 percent to 10
percent have the inherited BRCA mutation.
The study also found that breast cancer risks were significantly higher
for women who had the mutation and were born after 1940 than those in the
same family born before that year, suggesting nongenetic influences - such
as an early first pregnancy, already known to reduce a woman's risk of
breast cancer - in development of the cancer.
The study looked at patients from 12 cancer centers in New York who were
diagnosed with breast cancer between 1996 and 2000. The women were of
European Jewish heritage because that population is known to harbor only
three types of BRCA mutation. King said this limited variety of mutations
made the complex study "technically more feasible."
The study said, however, that the results are probably applicable to any
women with BRCA1 and BRCA2 mutations "who have similar lifestyles."
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