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Untitled Document
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| Breast
and Ovarian Cancer |
Genes Can Cause Breast and
Ovarian Cancer |
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By
Kathleen Fergus,
MS, CGC and Jill
Simonsen
Reviewed
by Beth Crawford,
MS, CGC
Last
updated August 24, 2000
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Since
the early 1970s, doctors and scientists have known that
between 5 and 10 percent of breast cancer
cases are caused by inherited factors. In 1994, they
discovered a single gene
that when mutated,
appeared to greatly increase a person's chances of developing
breast cancer. The discovery of this gene — BRCA1
— was quickly followed by the discovery of another
gene — BRCA2 — that
also predisposes people to breast cancer. In the intervening
years, researchers have discovered that mutations in
these genes account for the majority of not only hereditary
breast cancers but hereditary ovarian cancers as well,
and that these mutations are more common in people of
Ashkenazi Jewish descent
than in other groups.
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BRCA1
and BRCA2: Their Function
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| BRCA1
and BRCA2 are thought to be important to correct
mistakes that occur in DNA when cells divide. |
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Researchers
used to think that the BRCA1 and BRCA2 genes were tumor
suppressor genes. Although
researchers are still trying to understand precisely
how the two genes function, they now believe that they
may actually be what are called mismatch repair genes. (For recent news about the role of BRCA2, see Related News below.)
To understand what's meant by this,
you need to understand a little bit about the cell replication
process that occurs constantly within our bodies. As
our cells age and die, new cells must be made to replace
them. For this to happen, each of the three billion
letters of DNA
that are found within every cell has to be copied —
one letter at a time. Not surprisingly, mistakes sometimes
occur. When this happens, a gene may stop making its
protein or the the protein can cease to function normally.
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click
image for larger representation
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To ensure
that such mistakes don't accumulate, our body has special
proteins — called mismatch repair proteins —
that check for and then correct mistakes in the newly
made DNA. The genes that produce these special proteins
are called mismatch repair genes — and it is in
two of these genes (BRCA1 and BRCA2) that researchers
have discovered the mutations most commonly linked with
breast and ovarian cancer.
When
a person's mismatch repair genes aren't functioning
properly, they may not be able to catch and correct
those inevitable DNA copying mistakes. And when such
mistakes occur in genes whose function it is to prevent
a cell from becoming cancerous, malignancies
can occur.
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 top
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BRCA1
and BRCA2 Mutations and Cancer Risk
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Although
the BRCA1 and BRCA2 genes appear to be similar in function,
they are located on different chromosomes,
and each, when mutated, confers varying degrees of risk,
not only for inherited breast and ovarian cancer but
for other types of cancer as well. The types of cancer
associated with mutations in the BRCA1 and BRCA2 genes
are as follows:
- BRCA1.
Mutations in the BRCA1 gene appear to increase an
individual's risk for breast, ovarian, prostate, and
possibly colon cancer.
- BRCA2.
Mutations
in the BRCA2 gene appear to increase an individual's
risk for breast (male and female), ovarian, prostate,
and pancreatic cancers. In addition, researchers suspect
that defects in this gene carry with them an increased
risk for cancer of the lung, larynx (voice box), and
skin; however, more studies are needed to confirm
these associations.
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| Researchers
are still trying to determine the exact risk of
cancer that is conferred by carrying a mutation
in the BRCA1 or BRCA2 gene. |
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Early
studies indicated that 80 percent of women who had inherited
mutations in either of these genes would one day develop
breast cancer, and that 60 percent would eventually develop
ovarian cancer. However, these numbers were based on data
collected from women in high-risk families (that is, those
in which several cases of cancer had already been diagnosed).
As researchers have expanded their studies to include
members of the general population, they are discovering
that risk associated with having a mutation in BRCA1 or
BRCA2 may actually be lower than initial studies indicated.
For this reason, the degree of risk associated with these
mutations is now most commonly expressed as a range of
numbers rather than an absolute — at least until
enough data exists to make better estimates.
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More on Breast and Ovarian Cancer Risk in Women With BRCA1 and BRCA2 Mutations (Coming soon)
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Type
of Cancer
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Percent
of General Population That Will Develop Disease
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Percent
of Those With BRCA1 Mutation Who Will Develop
Disease
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Percent
of Those With BRCA2 Mutation Who Will Develop
Disease
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Breast
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12.5%
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55%
to 85%
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33%
to 86%
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Ovarian
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1.43%
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28%
to 44%
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10%
to 30%
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Prostate
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4.5 to 6.0%
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12%
to 18%
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12%
to 18%
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Male
Breast Cancer
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Less
than 1%
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6%
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4%
to 14%
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Pancreatic
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0.6%
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n.a.
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6%
to 7%
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References
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Claus,
E. B. et al. (1991). Genetic analysis of breast cancer
in the cancer and steroid hormone study. Am J Hum
Genet 48: 232-42.
Hoskins, K. F. et al. (1995). Assessment and counseling
for women with a family history of breast cancer. A
guide for clinicians. JAMA 273(7): 577-85.
Houlston, R. S. et al. (1992). Family History and Breast
Cancer. J Med Genet 29: 154-157.
Rajan, J. V. et al. (1997). Developmental expression
of Brca2 colocalizes with Brca1 and is associated with
proliferation and differentiation in multiple tissues.
Dev Biol 184(2): 385-401.
Rajan, J. V. et al. (1996). Brca2 is coordinately regulated
with Brca1 during proliferation and differentiation
in mammary epithelial cells. Proc Natl Acad Sci USA
93(23): 13078-83.
Scully, R. et al. (1997). BRCA1 is a component of the
RNA polymerase II holoenzyme. Proc Natl Acad Sci
USA 94(11): 5605-10.
Slattery, M. K. R. (1993). A Comprehensive evaluation
of family history and breast cancer risk: the Utah Population
Database. JAMA 270: 1563-68.
Tonin, P. et al. (1996). Frequency of recurrent BRCA1
and BRCA2 mutations in Ashkenazi Jewish breast Cancer
Families. Nature Medicine 2: 1179-1183.
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