- BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins which help repair damaged DNA.
- BRCA gene mutations can raise the risk for several cancers, including breast, ovarian, prostate, and pancreatic cancer.
The BRCA1 gene is required for the survival of blood forming stem cells. Patients with BRCA1 mutations do not have an elevated risk for leukemia. The stem cells die before they have an opportunity to transform into a blood cancer.
"One of the great mysteries in cancer research is why inherited mutations, such as those in BRCA1, cause cancer only in specific tissues such as the breast and ovaries, rather than in all tissues. Our data suggest a 'die or transform' hypothesis, which could explain this tissue specificity," said Dr. Theodora Ross, Professor of Internal Medicine and Director of the Cancer Genetics Program at UT Southwestern.
Additional data from this study suggest these patients may have a tougher time with the side effects of chemotherapy. "Patients with certain BRCA1 mutations may be at a higher than expected risk for serious complications during chemotherapy treatment," said Dr. Ross, who holds the Jeanne Ann Plitt Professorship in Breast Cancer Research and the H. Ben and Isabelle T. Decherd Chair in Internal Medicine in Honor of Henry M. Winans, Sr., M.D.
According to the National Cancer Institute, more than 246,660 women will be diagnosed with breast cancer and 22,280 women will be diagnosed with ovarian cancer this year. Of these, about 10-15 percent are estimated to be affected by BRCA1 and BRCA2 genetic mutations, Dr. Ross said.
"Our data also illustrate why rare variations in the BRCA1 gene are not always mutations that put women and men at high risk for specific cancers. We and others have learned that most rare spellings of the BRCA1 gene, spellings we call variations of undetermined significance, are not harmful," said Dr. Ross, a member of the Simmons Cancer Center.
Dr. Ross' laboratory investigates how cells transform from normal cells to cancer cells, and how some cancer cells are able to withstand specifically targeted cancer drugs. Among her main avenues of research is the BRCA1 gene, which - when abnormal - predisposes women to breast and ovarian cancer.
- Theodora Ross et al., Researchers discover BRCA1 gene is key for blood forming stem cells, Cell Reports (2017).