Researchers have found a new gene called HMMR that, when mutated, may lead to a significantly greater chance of developing breast cancer. The study was a collaboration of international researchers from Spain, Israel, and several U.S. organizations.
The HMMR gene is mutated in about 10% of the population, while two other genes related to breast cancer, BRCA1 and CRCA2, are mutated in only about 0.3% of the popuation. According to the study’s authors, it’s important to identify more common breast cancer-related genes so that targeting the gene for early detection will have a greater impact.
The method of identifying the HMMR gene began with computer modeling to identify genes that impact cancer development and to see how they interact with other genes. Starting with four known breast cancer-related genes (BRCA1, BRCA2, ATM and CHEK2), researchers then showed that alterations of either BRCA1 or HMMR can lead to genetic instability and interfere with cell division.
To specifically understand whether variations in HMMR increased breast cancer risk, 923 women with breast cancer and similar women without breast cancer were analyzed in a study led by Gadi Rennert, M.D., director of the CHS National Cancer Control Center in Haifa, Israel. The results indicated that women in the study under 40 years of age with the HMMR variant (even after accounting for mutations in the BRCA1 or BRCA2 genes), had a 2.7 times greater risk of developing breast cancer than women without the variation.
The study was conducted among a population of Ashkenazi Jewish women, who have a higher risk of breast cancer than other groups.
The findings were verified in two other studies conducted in New York–one among another group of Ashkenazi Jewish women with a family history of breast cancer but no identified BRCA1 or BRCA2 mutations, and a third study of Jewish women with and without breast cancer in New York. Overall, 2,475 women with breast cancer and 1,918 healthy women were studied in Israel and New York.
The findings indicated that incidence of breast cancer was 23% higher in women who had one copy of the genetic variant, and 46% higher in women who had two copies of the variant. Researchers also concluded that HMMR may be associated with early-onset breast cancer, as the women with the HMMR variant were diagnosed about one year earlier than the control group.
"Identifying genes involved in cancer in the general population is important, because not all of the causes of breast cancer have been found. Through discoveries such as this, someday we might be able to more precisely estimate a person’s risk of cancer based on their genes," says study author Laura Rozek, Ph.D., a postdoctoral research fellow at the University of Medical School.
The study was funded by the National Cancer Institute, the National Institutes of Health, the Breast Cancer Research Foundation, the Niehaus, Southworth, Weissenbach Foundation, and the Koodish Foundation.
Sources: Nature Genetics, doi:10.1038/ngxxxx and University of Michigan