SALT LAKE CITY— Four new genes have been added to the growing list of those known to cause increased breast cancer risk when mutated through the efforts of researchers at Huntsman Cancer Institute (HCI) at the University of Utah, who lead an international consortium working to find more gene mutations that cause inherited breast cancer susceptibilities.
"BRCA1 and BRCA2 aren't the whole story when it comes to inherited breast cancer risk. We've known for a long time that more genes had to be responsible and several have since been discovered, 被大发娱乐和其他人,根据… 肖恩·塔夫蒂吉安博士.D., HCI调查员, professor in the Department of Oncological Sciences at the University of Utah (U of U), and one of three joint-principal investigators on the study. “最初, the gene we are currently studying, 叫RINT1, was not considered a human cancer susceptibility gene. But then we discovered there was a two- to three-fold increase in risk for breast cancer in families that carry a mutation in that gene." The RINT1 findings were published in the May issue of the journal Cancer Discovery.
令人惊讶的是, RINT1 was also found to increase risk for a broad spectrum of gastrointestinal and gynecological cancers in these families. "Many genes responsible for a strong increase in cancer risk at one or two sites in the body are also connected with lesser increases in risk at other sites,大卫·戈德加说, Ph.D., professor in the Department of Dermatology at 大学中的大学, HCI调查员, and another of the study's joint-principal investigators. “然而, 有RINT1突变, the increased risk for other cancers is about equal to that for breast cancer."
In another study led by Tavtigian, mutations in three other genes—MRE11A, RAD50, and NBN—were also confirmed to increase breast cancer risk, as reported in this month's issue of the journal Breast Cancer 研究. "The proteins encoded by these three genes form a tight complex that is involved in DNA repair, and the three genes had been considered likely candidates. 有趣的是, RINT1's name is an abbreviation for ‘RAD50 Interactor 1,' and it's just one step downstream from the MRE11A, RAD50, NBN complex in a biochemical sense,塔夫蒂吉安说. "But we don't know yet if that biochemical connection explains RINT1's cancer susceptibility role."
Now almost 50% of the familial risk for breast cancer can be explained by the ensemble of rare mutations in known breast cancer susceptibility genes and more common genetic variation in about 75 areas of the genome each of which is associated with only a small increased risk of breast cancer according to Goldgar, compared to about 30% only five years ago. The consortium's ongoing efforts continue to enlarge the panel of genes known to account for increased occurrence of breast cancer within families with a history of the disease.
梅丽莎·C. 骚塞,Ph值.D., professor in the Department of Pathology at the University of Melbourne, 澳大利亚, is the third joint-PI on the study that led to RINT1, and is a co-investigator on the other study. Between them, the two articles list nearly 50 co-authors from HCI (including Kayoko Tao, Ph.D., co-first author of the RINT1 paper), 大学中的大学, and other research organizations based in North America, 澳大利亚, 和欧洲. Funding from the National Institutes of Health (R01CA155767, R01CA121245, 和P30CA042014), the Breast Cancer Family Registry, Huntsman Cancer Foundation, and many worldwide cancer research foundations supported the studies.
关于 Huntsman Cancer Institute at the University of Utah
Huntsman Cancer Institute (HCI) is one of the world's top academic research and cancer treatment centers. HCI管理 Utah Population Database — the largest genetic database in the world, with more than 16 million records linked to genealogies, 健康记录, 生命统计数据. 使用这些数据, HCI researchers have identified cancer-causing genes, including the genes responsible for melanoma, 结肠 and breast cancer, 和副神经节瘤. HCI is a member of the National Comprehensive Cancer Network (a 23-member alliance of the world's leading cancer centers) and is a National Cancer Institute-Designated Cancer Center. HCI treats patients with all forms of cancer and operates several high-risk clinics that focus on melanoma and breast, 结肠, 还有胰腺癌. The HCI Cancer Learning Center for patient and public education contains one of the nation's largest collections of cancer-related publications. The institute is named after Jon M. 老猎人,., a Utah philanthropist, industrialist, and cancer survivor.