Scientists have had limited success at identifying specific inherited genes associated with 前列腺癌, despite the fact that it is one of the most common non-skin 癌症s among men. 研究人员 大发娱乐 研究多种癌症诊断的前列腺癌患者, many who would not be recommended for genetic tests following current guidelines, to identify genetic mutations that may influence 癌症 treatment and 癌症 risk assessment for family members. 他们的研究结果发表在6月份的《大发娱乐》杂志上 癌症.
"We commonly use a combination of a patient's personal and family 癌症 histories to identify those individuals who may have a mutation in a gene that predisposes that individual to developing 癌症s,帕特里克·皮利说, M.D., medical oncology fellow at the University of Texas MD Anderson 癌症 Center. "Testing for hereditary 癌症s impacts not only the patient with 癌症 but also potentially the 癌症 screening and health outcomes of their entire family, but many 前列腺癌 patients do not meet the current guidelines to test for genetic 癌症 heritability."
皮里格尔是凯瑟琳·库尼（Kathleen Cooney）领导的一个研究小组的成员.D., chair of the Department of Internal Medicine at U of U Health and a Huntsman 癌症 Institute investigator, who proposed a strategy to identify germline mutations in men selected for the study based on their clinical history not their family history.
这项研究是高度选择性的, including 102 patients who had been diagnosed with 前列腺癌 and at least one additional primary 癌症, 像黑素瘤, 胰腺癌, 睾丸癌, 或霍奇金淋巴瘤.
The researchers examined the frequency of harmful germline mutations in this group of men. These mutations originate on either the egg or sperm and become incorporated into the DNA of every cell in the body of the resulting offspring.
使用下一代测序, the researchers found that 11 percent of the patients had a disease-causing mutation in at least one 癌症-predisposing gene, which suggests these genetic variations contributed to their 前列腺癌. Cooney found no difference in 癌症 aggressiveness or age of diagnosis compared to patients without these mutations.
除了, a certified genetic counselor and co-investigator Elena Stoffel, M.D., 密歇根大学综合癌症中心, reviewed personal and family histories from each patient to determine whether they would meet clinical genetic testing guidelines. 研究中的大多数男性, 64%, did not meet current criteria to test for hereditary 癌症 based on personal and/or family history.
The findings suggest that there are men with heritable 前列腺癌-predisposing mutations that are not eligible for genetic screening under current guidelines.
"This is the first paper in which we can show the potential of using a clinical history of multiple 癌症s, 包括前列腺癌, 在单个个体中识别遗传的种系突变,库尼说。.
The majority of harmful mutations identified were in genes involved in DNA repair.
“这些突变阻止了DNA的自我修复, 什么会导致患癌症的倾向,库尼说。.
This result is also beneficial because drugs like PARP [poly ADP ribose polymerase] inhibitors have a better success rate in treating 癌症s with the underlying gene mutation associated with DNA repair.
Cooney cautions that this is a small pilot study rather than a broader epidemiological survey, 它由一个高度特定的病人子集组成.
“大发娱乐不能将这些发现推广到更广泛的人群, because we used highly selective criteria to tip us off to patients that may have mutations outside typical hereditary genetic patterns,她说.
The 102 patients included in the study were identified from the University of Michigan's Prostate 癌症 Genetics Project, 哪些机构会登记被诊断患有糖尿病的病人 前列腺癌 before age 55 or who have a first- or second-degree relative with 前列腺癌. 除了, the research team identified patients from the University of Michigan's 癌症 Genetics Registry, which includes individuals with personal or family history suggestive of a hereditary risk of 癌症.
“大发娱乐的发现与其他研究结果一致, suggesting that approximately 1 in 10 men with advanced 前列腺癌 harbors a genetic variant associated with increased 癌症 risk,斯托费尔说. “虽然家族史是一个重要的工具, there may be better ways to identify patients with genetic risk."
Future studies with larger sample sizes will include sequencing of tumors that will allow investigators to more carefully explore the different features associated with tumors that arise in individuals with germline mutations.
"This approach will help us identify patients at greater risk for aggressive 前列腺癌 so they can seek earlier screening while pre-symptomatic,库尼说。.
除了犹他大学健康中心, collaborating institutions include University of Texas MD Anderson 癌症 Center, University of Michigan Medical School and 密歇根大学综合癌症中心. This research was supported by a grant from the University of Michigan Prostate 癌症 Specialized Program of 研究 Excellence (SPORE) and the 密歇根大学综合癌症中心 Sequencing Core.