introduction
Breast cancer is by far the most common cancer affecting women worldwide, and it is the most common cause of cancer death in women. In the United States, approximately 1 in 8 women will be diagnosed with breast cancer during her lifetime.
If diagnosed early, breast cancer can be treated very successfully. The five-year survival rate for women diagnosed with the earliest stages of breast cancer is close to 99%. Early diagnosis and treatment is crucial in the management of breast cancer.
Genetic factors contribute significantly to the risk of developing the disease. In addition to variants in the BRCA1 and BRCA2 genes, which are rare variants, present in only 2-5% of breast cancer patients, eight genetic variants have been found to increase the risk of developing breast cancer: on chromosomes 2 and 8, in or near the FGFR2 gene on chromosome 10, in the TNRC9/TOX3 genes on chromosome 16, in the LSP1 gene on chromosome 11, near the MRPS30 and MAP3K1 genes on chromosome 5, and in the CASP8 gene on chromosome 2.
The deCODEme Genetic Scan identifies the eight common genetic variants and provides interpretation of their associated risk for the development of breast cancer. These variants are on chromosomes 2, 5, 8, 10, 11, 15 and 16. All eight variants are identified in individuals of European descent, whereas in East-Asians the deCODEme Genetic Scan currently identifies three out of the eight variants; on chromosomes 5 (MAP3K1), 10, and 16. At the present time no risk estimation data are available for people of other ethnicities for the variants above.
risk factors
The two primary classes of known risk factors for breast cancer are hormonal factors and genetics factors:- Hormonal factors: During a woman’s menstrual cycle, the levels of the hormones estrogen and progesterone increase and decrease in a set pattern. Estrogen is known to cause abnormal growth of breast tissue. During a woman’s lifetime, she will experience around 450 menstrual cycles and be exposed to increased levels of estrogen with each cycle. Factors that increase the lifetime exposure to estrogen tend to increase breast cancer risk:
- Age is one of the strongest risk factors. Breast cancer is quite rare in women under 35, while the risk is considerably higher in women over 60.
- Delaying childbirth also increases risk by increasing the total number of menstruation cycles over a woman’s lifetime.
- For similar reasons, menstruation that begins early in life (before age 12) and late menopause (after age 55) significantly increase breast cancer risk.
- Long-term use of hormone replacement therapy, which includes estrogen, also increases breast cancer risk.
- Genetic factors: Genetic factors play a contributing role in the majority of breast cancer cases.
Having two or more close blood relatives with breast or ovarian cancer may indicate the presence of a mutation (a damaging change) in a gene that is associated with an exceptionally high risk of breast cancer, such as the BRCA1 or BRCA2 genes. Mutations that are associated with these very high risks of breast cancer are present in only a small percentage of breast cancer patients (2-5%). Please note that the deCODEme Genetic Scan does not test for BRCA1 or BRCA2 variants, and the possibility of having these variants should be discussed with a doctor
(see Myriad Genetics for more information).
In addition to rare mutations in the BRCA1 and BRCA2 genes, there are several more common gene variants that carry less risk but play a role in a much larger proportion, if not all, breast cancer cases. Eight genetic variants have been found to increase the risk of developing breast cancer: on chromosomes 2 and 8, in or near the FGFR2 gene on chromosome 10, in the TNRC9/TOX3 genes on chromosome 16, in the LSP1 gene on chromosome 11, in or near the MAP3K1 and MRPS30 genes on chromosome 5, and in the CASP8 gene on chromosome 2. While each of these variants on its own is associated with only a small increase in risk of breast cancer, the combined risk can be high if a person inherits many of these variants. Combinations of these common breast cancer risk variants may be difficult to trace through a family’s history.