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The latest observational study of genomic data in women indicates that the location and type of mutation in BRCA genes play crucial roles in the odds of women getting breast or ovarian cancer. It has long been known that women who carry the BRCA1 or BRCA2 gene mutations are at increased risk for developing these cancers, however the new study, published today in the Journal of the American Medical Association (JAMA), goes into greater detail in identifying the specific mutations in these genes and the risks they create.

Mutations on BRCA1 Gene

Mutations on the BRCA1 Gene (Image courtesy NCI)

Preventive surgery with mastectomy (removal of breasts) or salpingo-oophorectomy (removal of ovaries and fallopian tubes) reduces a woman’s risk of breast and ovarian cancer by over 90%. Actress Angelina Jolie publicized her own story in 2013 of discovering a BRCA1 mutation, and her subsequent decision to have a double mastectomy to lower her future risk of cancer. But some women with BRCA1 or BRCA2 gene mutations will not develop cancer, thus more research is needed to help women make these critical decisions.

Today’s JAMA study, written by an international group of researchers, pooled data from 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. The data collected goes back almost 80 years, to 1937.

The study shows that among women with BRCA1 mutations, 46% are eventually diagnosed with breast cancer, 12% with ovarian cancer, and 5% with both. 37% of women with such mutations did not develop any cancer. Among women with the BRCA2 mutations, 52% were diagnosed with breast cancer, 6% with ovarian cancer, and 2% with both, while 40% did not develop cancer. This data backs up similar odds produced in a large study reported in JAMA by Israeli researchers in 2014.

Additionally, today’s study further identified 3 breast cancer and 1 ovarian cancer “cluster regions” for BRCA1, and another 3 cluster regions for each cancer in BRCA2. This information provides researchers a more detailed roadmap for determining specific cancer risks from BRCA1 and BRCA2 mutations. In the near future, screening for women may be able to better pinpoint the risk of breast and ovarian cancer to help women make the important decisions over prophylactic surgery.

Location of the BRCA1 gene on chromosome 17

Location of the BRCA1 gene on chromosome 17 (“BRCA1_en.png” by Kuebi (Armin Kübelbeck) / CC BY-SA 3.0)

BRCA1 and BRCA2, both identified in the early 1990s, are tumor suppressor genes, which when functioning normally, produce proteins which help control proper cell growth. Their proteins repair damaged DNA or destroy cells if the DNA can not be repaired. BRCA1 and BRCA2 are structurally different and located on different chromosomes, but are often discussed together because of their similar functions. Mutations in these genes allow a greater risk of developing breast, ovarian, and other types of cancer.

Prior to 2010, the publicly traded company Myriad Genetics in Salt Lake City, Utah, enforced their patents on the BRCA1 and BRCA2 genes, which many scientists argued stifled research and resulted in profoundly high prices for screening (e.g. $4,000 USD per test). Although researchers at the University of California, Berkeley, first discovered the location of BRCA1 on chromosome 17, Myriad was first able to sequence the gene. In June, 2013, in the landmark, unanimous decision of the US Supreme Court in Association for Molecular Pathology v. Myriad Genetics, Inc., the court held that a “naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.” At the time of this ruling, the US Patent and Trademark Office had already granted thousands of patents for human genes, accounting for almost 20% of the human body. Patent holders were previously given the right to prevent other researchers from studying a patented gene. It is entirely possible that research such as today’s JAMA paper would not be possible were it not for this ruling.