Christopher Haiman, associate professor of preventive medicine at the Keck School, served as co-principal investigator for the study, which appeared online in Nature Genetics. Fergus Couch, professor of laboratory medicine and pathology at the Mayo Clinic, served as co-principal investigator.
Research led by Christopher Haiman has identified the location of a genetic risk factor for a special type of breast cancer.
The investigative team was searching for genetic risk factors associated with what is known as estrogen receptor (ER)-negative breast cancer, a form of the disease that is deficient in expressing the estrogen receptor and therefore does not respond to drug treatments targeting the receptor in breast tissue.
Women of African descent are more likely to have this type of breast cancer than women from other racial and ethnic backgrounds, according to the researchers. They also are more at risk for triple-negative breast tumors, which are deficient in expressing progesterone receptor and human epidermal growth factor-2 receptor, as well as the estrogen receptor. Triple negative breast cancer is an even more aggressive tumor subtype associated with a poor prognosis and decreased survival rates.
In pursuing genetic clues to these diseases, the researchers combined results from two large studies: a genome-wide scan of breast cancer in African-American women and a study of women with European ancestry who had triple-negative breast cancer.
“Our results demonstrate a genetic basis for estrogen receptor-negative breast cancer subtypes in multiple populations,” Haiman said. “We found a common allele [an inherited variation in the DNA sequence] near the TERT gene on chromosome 5, which was significantly associated with an increased risk of ER-negative breast cancer.”
Haiman, whose primary research focuses on understanding genetic susceptibility to breast and prostate cancer in minority populations, added that “this genetic variant showed a greater association with triple-negative tumors, especially among women under age 50. This tells us that there are susceptibility regions for triple-negative breast cancer. These and other regions may help us to understand the greater risk of estrogen receptor-negative and triple-negative disease in women of African ancestry.”
Couch explained that the region of the genome they studied has been the focus of investigations of other cancers as well, including serous ovarian cancer, glioma and lung cancer.
“So this might be a global marker for other cancers besides ER-negative breast cancer,” said Couch, whose research focuses on familial/inherited forms of breast, ovarian and pancreatic cancer.
Haiman said researchers now need to continue the search for genetic risk factors for these aggressive tumor subtypes.
“We plan to enlarge this study with other genome-wide research that is also focused on estrogen receptor-negative disease in order to identify additional susceptibility regions for this important breast-cancer subtype,” he said. “Identification of additional susceptibility regions for aggressive forms of breast cancer will continue to inform us about the etiology and biology of these tumors and, hopefully, provide new information that can be used for screening, prevention and targeted treatment.”
The research was supported by funding from the U.S. Department of Defense, the Kenneth T. and Eileen L. Norris Foundation, the Mayo Clinic College of Medicine, Susan G. Komen for the Cure, the Breast Cancer Research Foundation and the National Institutes of Health.