Ashkenazi Jews and Breast Cancer
In American women, about 5 to 10 percent of all breast cancer cases are hereditary in nature, being passed from one generation to the next. Most of these inherited forms of breast cancer can be attributed to mutation in two genes, namely BRCA1 (breast cancer type 1 susceptibility protein) and BRCA2 (breast cancer type 2 susceptibility protein), present on chromosome 17 and chromosome 13 respectively.
Although BRCA1 and BRCA2 genes are present in everyone and help to repair DNA damage, it is when they undergo some mutation that the risk of breast cancer increases. A woman who has inherited a mutated BRCA1 or BRCA2 gene has 80 percent risk of being diagnosed with breast cancer in her lifetime, which is five times more as compared to a woman who has not inherited these mutated genes. A study found that the risk of breast cancer among the carriers of one of the three types of mutations in these genes is 33 percent by the age of 50 and 56 percent by the age of 70.
Origin of Ashkenazi Jews and High Risk of Breast Cancer
The term “Ashkenazi” means “Germany” in Hebrew and Ashkenazi Jews (Ashkenazim) are the descendants of Jews from Eastern and Central Europe, such as Germany, Poland, Lithuania, Ukraine, and Russia. They have migrated all over the world and in the United States, 9 out of every 10 Jewish American are of Ashkenazi Jewish descent.
It has been found that the incidence of mutated BRCA1 and BRCA2 genes is far more common in women of Ashkenazi Jewish descent as compared to general population. It is mainly due to the “founder effect”. The founder effect occurs in groups that have originated from a small number of common founders (ancestors). The BRCA1 and BRCA2 mutations are believed to have taken place in this Jewish community about 600 years ago.
As these Jews remained isolated for a long period of time because of certain political and religious reasons, they were also genetically isolated from other groups. Therefore, inherited mutations of BRCA1 and BRCA2 genes have been passed down to the subsequent generations with greater frequency and are found far more commonly in Ashkenazi Jews. As compared to 0.2 percent chance of mutation of these genes in general population, almost 2.3 percent of Ashkenazi Jews carry these mutated genes.
There are two mutations in BRCA1 gene and one mutation in BRCA2 gene which increase the risk of breast cancer. There is a 70 percent chance of developing breast cancer in carriers of BRCA1 mutation (5382insC or 185delAG), whereas carriers of BRCA2 mutation (6174delT) have a 50 percent risk of breast cancer.
In a study to investigate the extent to which the mutations in BRCA genes contribute to breast cancer incidence in the Ashkenazi Jewish population, 457 women were selected and 412 of them underwent testing. The researchers found mutation of BRCA genes in 48 of these women. Of these 48 women, 46 women with early-onset breast cancer (<50 years), or a history of ovarian, or early-onset breast cancer in a first-, second-, or third-degree relative tested positive for a gene mutation. Nearly 59.9 percent had a BRCA1 gene mutation while 28.3 percent had a BRCA2 gene mutation, when analyzed up to the age of 70.
Incidence of BRCA1/2 Gene Mutation in Familial Patterns of Breast Cancer
Certain familial patterns of cancer are more likely to show a mutation of BRCA genes. For Ashkenazi women, a high risk of family history includes any first-degree relative (or two second-degree relatives on the same side of the family) with breast or ovarian cancer. The penetration of BRCA gene mutation in case of a positive history of cancer in the family of Ashkenazi Jews has been found to be as follows:
- 20 percent of the Ashkenazi Jews who developed breast cancer before the age of 40 were found to have a BRCA1 mutation.
- 29 percent of Ashkenazi Jews carried mutation in one of the BRCA genes when there was a family history of two or more cases of breast cancer.
- 73 percent of Ashkenazi Jews were found to be carrying one of the BRCA gene mutations when there was a family history of two or more cases of breast cancer and at least one case of ovarian cancer.
A study by Metcalfe et al, has proposed that owing to the high incidence of BRCA gene mutations found in women of Ashkenazi descent, a general population screening in these women should be considered. This is all the more important because over half of unaffected Ashkenazi Jewish BRCA1 or BRCA2 carriers cannot be identified by relying solely on family history. There are many examples of development of random cancer without any positive family history. It should not be assumed that unaffected siblings cannot be carriers. The researchers of another study concluded that a population screening of Ashkenazi Jews for BRCA gene mutations will be a cost effective exercise as it will help in detecting many cases of BRCA gene mutations which may lead to the development of breast cancer.
Advantages of Studying the Relationship between Ashkenazi Jews and BRCA1/2 Gene Mutation
The knowledge about the BRCA genes and their associated clinical consequences has increased after researches on Ashkenazi Jews. The studies have helped in gaining knowledge about the prevalence and penetration of BRCA1 and BRCA2 mutations, clarified doubts regarding inherited susceptibility, and led to improvement in diagnosis and treatment of breast cancer. Genetic screening has been made accessible to Ashkenazi women at a fraction of the cost offered to the general population. This has made them more likely to undergo genetic testing for identification of mutant BRCA1/2 genes. Easier access to testing has led to increased prophylactic oophorectomies and mastectomies, and chemoprevention, thereby reducing the risk of breast cancer in carriers of mutant BRCA1 and BRCA2 genes.
Drawbacks of Studying the Relationship between Ashkenazi Jews and BRCA1/2 Gene Mutation
Giving too much attention to BRCA1 and BRCA2 researches on Ashkenazi Jews has had its flip sides too. It has limited the attention given by the researchers to other ethnic groups. Physicians are less enthusiastic to recommend, and women of other ethnic groups are less likely to ask, for a genetic screening. This can lead to a poor identification of mutant BRCA carriers in women of other groups, some of whom are at an increased risk of developing breast cancer. These women are, as a result, less likely to undergo preventive treatment for breast cancer. Paying more attention to the Ashkenazi Jews has led to a reduction in the incidence of breast cancer in them. However, the incidence of breast cancer in the non-Jewish population has remained more or less static.
- 1. Brandt-Rauf, S. I., V. H. Raveis, N. F. Drummond, J. A. Conte, and S. M. Rothman. “Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease.” American Journal of Public Health 96.11 (2006): 1979-988. Print.
- 2. ”Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility.” Annals of Internal Medicine. Web. 20 Sept. 2011.
- 3. Katherine H Saunders. “Case Report: BRCA in the Ashkenazi Population: Are Current Testing Guidelines Too Exclusive?” Hereditary Cancer in Clinical Practice. Web. 20 Sept. 2011.
- 4. Metcalfe, K. A., A. Poll, R. Royer, M. Llacuachaqui, A. Tulman, P. Sun, and S. A. Narod. “Screening for Founder Mutations in BRCA1 and BRCA2 in Unselected Jewish Women.” Journal of Clinical Oncology 28.3 (2010): 387-91. Print.
- 5. Struewing JP. “The Risk of Cancer Associated with Specific Mutations of BRCA1 and BRCA2 among Ashkenazi Jews.” (1997). The New England Journal of Medicine. Web. 20 Sept. 2011.
- 6. Turkington, Carol, and Karen J. Krag. The Encyclopedia of Breast Cancer. New York: Facts On File, 2005. 16-17. Print.
- 7. Warner E. “Prevalence and Penetrance of BRCA1 and BRCA2 Gene Mutations in Unselected Ashkenazi Jewish Women With Breast Cancer.” Journal of the National Cancer Institute. Web. 20 Sept. 2011.