Oklahoma City, OK – Young women concerned about their risk for breast cancer may soon have another test to aid them in early detection or prevention of the disease, thanks to the discovery of another gene that appears to be associated with breast cancer in women age 50 and younger who have a family history of the disease.
The discovery, made by a joint Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center research team, is a variant gene that may indicate a risk for breast cancer in young women that is as high as the risk associated with the well-known genes, BRCA1 and BRCA2. The results of the study, which was funded by the Presbyterian Health Foundation, the American Cancer Society and the Oklahoma Center for the Advancement of Science and Technology, are published in the May 19, 2001, issue of The Lancet, a prestigious United Kingdom-based, international journal of medical science and practice.
“BRCA1 and BRCA2 are two genes already identified that account for some familial occurrences of breast cancer,” said Eldon Jupe, senior research scientist in the Oklahoma Medical Research Foundation Immunology and Cancer Program. “Researchers have been looking for other genes associated with the disease, and the T allele of prohibitin seems to be another gene marker that accounts for a number of breast cancer cases, specifically in women under 50 who have a moderate family history of the disease.”
The study was initiated by Jupe, who also is an adjunct associate professor of surgery at the OU Health Sciences Center, after he discovered an irregularity in the prohibitin gene, which has been associated with tumor-suppressing antiproliferative cell activity. To help him study the irregularity and its effect on those who carry it, Jupe, who served as the principal investigator of the study, joined with Linda F. Thompson of the OMRF Immunobiology and Cancer Program; Allen A. Badgett and Christopher E. Aston, also of OMRF; John J. Mulvihill, director of the OU Health Sciences Center Program in Human Genetics; Debra S. Mitchell and Melissa A. Craft of the OU Health Sciences Center Institute for Breast Health; Barbara R. Neas of the OU Health Sciences Center Department of Biostatistics and Epidemiology; and Regina Resta, formerly of the OU Health Sciences Center Hematology/Oncology Section.
“The earlier breast cancer is detected, the better chance of survival,” said Mulvihill. “Most patients fully recover from breast cancer if it is detected early, which is why we use genetic testing to help identify women who are at a higher risk.” According to Mulvihill, current genetic testing for the BRCA1 and BRCA2 genes only addresses approximately 8 percent of all breast cancer cases. Based on the preliminary findings of this study, Mulvihill says that another 8 percent of breast cancers may be attributed to the inheritance of the T allele.
The prohibitin irregularity, the T allele, seemed to lack the antiproliferative activity of the more common functional C allele, which led researchers to hypothesize that women who carried the prohibitin T allele may have an increased risk for breast cancer. To assess the association between the T allele and breast cancer, a study of 205 breast cancer patients and 1,046 control participants was initiated.
Among the patients and control participants who reported a mother or sister who had been diagnosed with the disease, 47 patients and 239 controls, a significantly increased percentage of the patients were found to be carriers of the T allele. In contrast, patients and controls who reported no first-degree relative with breast cancer, 158 patients and 807 controls, were found to have similar occurrences of the T allele.
Additional comparisons revealed that among the study’s breast cancer patients and control participants who reported a first-degree relative who also had been diagnosed with breast cancer, patients age 50 and younger were found to have a significantly higher occurrence of the T allele than controls age 50 and younger. Among individuals older than age 50, there was no meaningful difference in the occurrence of the T allele regardless of family history. The study also showed that carriers of the T allele were diagnosed with breast cancer an average of seven years earlier than non-carriers.
“Although the results still have to be verified, the findings suggest that prohibitin genotyping, a relatively easy and inexpensive test, could become an effective screening tool for improving the risk estimate of breast cancer in women with a family history of the disease,” said Jupe.
Thompson, who holds the Putnam City Schools Chair in Cancer Research at the Oklahoma Medical Research Foundation, added that the study, which awaits confirmation, also suggests that a more exact definition of genetic risk in women with a family history of breast cancer could help guide health-care decisions, such as the appropriate age at which women should begin mammography screening.
