Genetic risk factors

Genetic risk factors

About 5% to 10% of breast cancer cases are thought to be hereditary, resulting directly
from gene defects (called mutations) inherited from a parent. See the section, "Do we
know what causes breast cancer?" for more information about genes and DNA.
BRCA1 and BRCA2: The most common cause of hereditary breast cancer is an inherited
mutation in the BRCA1 and BRCA2 genes. In normal cells, these genes help prevent
cancer by making proteins that keep the cells from growing abnormally. If you have
inherited a mutated copy of either gene from a parent, you have a high risk of developing
breast cancer during your lifetime. The risk may be as high as 80% for members of some
families with BRCA mutations. These cancers tend to occur in younger women and more
often affect both breasts than cancers in women who are not born with one of these gene
mutations. Women with these inherited mutations also have an increased risk for
developing other cancers, particularly ovarian cancer.
In the United States BRCA mutations are more common in Jewish women of Ashkenazi
(Eastern Europe) origin than in other racial and ethnic groups, but they can occur in any
racial or ethnic group.
Changes in other genes: Other gene mutations can also lead to inherited breast cancers.
These gene mutations are much rarer and often do not increase the risk of breast cancer as
much as the BRCA genes. They are not frequent causes of inherited breast cancer.
· ATM: The ATM gene normally helps repair damaged DNA. Inheriting 2 abnormal
copies of this gene causes the disease ataxia-telangiectasia. Inheriting 1 mutated copy
of this gene has been linked to a high rate of breast cancer in some families.
· TP53: The TP53 gene gives instructions for making a protein called p53 that helps
stop the growth of abnormal cells. Inherited mutations of this gene cause Li-Fraumeni
syndrome (named after the 2 researchers who first described it). People with this
syndrome have an increased risk of developing breast cancer, as well as several other
cancers such as leukemia, brain tumors, and sarcomas (cancer of bones or connective
tissue). This is a rare cause of breast cancer.
· CHEK2: The Li-Fraumeni syndrome can also be caused by inherited mutations in the
CHEK2 gene. Even when it does not cause this syndrome, it can increase breast
cancer risk about twofold when it is mutated.
· PTEN: The PTEN gene normally helps regulate cell growth. Inherited mutations in
this gene can cause Cowden syndrome, a rare disorder in which people are at
increased risk for both benign and malignant breast tumors, as well as growths in the
digestive tract, thyroid, uterus, and ovaries. Defects in this gene can also cause a
different syndrome called Bannayan-Riley-Ruvalcaba syndrome that is not thought to
be linked to breast cancer risk.

· CDH1: Inherited mutations in this gene cause hereditary diffuse gastric cancer, a
syndrome in which people develop a rare type of stomach cancer at an early age.
Women with mutations in this gene also have an increased risk of invasive lobular
breast cancer.
· STK11: Defects in this gene can lead to Peutz-Jeghers syndrome. People with this
disorder develop pigmented spots on their lips and in their mouths, polyps in the
urinary and gastrointestinal tracts, and have an increased risk of many types of
cancer, including breast cancer.