A Genetic Linkage Study of Testicular Cancer

睾丸癌的遗传连锁研究

• 批准号: 7263062
• 负责人: Victoria K Cortessis
• 金额: $ 70.72万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-27 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7263062
• 关键词: AIDS related neoplasm; Adult; Alleles; Bilateral; Breast; Brothers; California; Cancer-Predisposing Gene; Candidate Disease Gene; Carcinoma; Cloning; Collaborations; Colon Carcinoma; Communication; Compatible; Condition; Contact Tracing; Cryptorchidism; DNA; Data; Data Linkages; Diagnosis; Disease; Enrollment; Epidemiologic Studies; Etiology; Family; Family history of; First Degree Relative; Frequencies; Funding; Future; Genes; Genetic; Genitourinary system; Genome; Genome Scan; Genotype; Germ Cells; Incidence; Individual; Infant; International; Invasive; Joints; Kaposi Sarcoma; Laboratories; Learning; Life; Link; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of testis; Maps; Measures; Neoplasms; Numbers; Pattern; Penetrance; Phenotype; Polymorphic Microsatellite Marker; Population; Prevalence; Procedures; Process; Questionnaires; Rate; Recording of previous events; Relative Risks; Research; Resources; Risk; Risk Factors; Sampling; Screening procedure; Series; Staging; Subgroup; Survivors; Susceptibility Gene; System; Testis; Text; Victoria Austrailia; Work; aged; base; gene cloning; gene discovery; gene environment interaction; genetic linkage; genetic linkage analysis; genome wide association study; genome-wide linkage; improved; interest; male; malformation; melanoma; member; men; neoplasm registry; positional cloning; response; segregation; tumor

DESCRIPTION (provided by applicant): Testicular cancer is a disease of very young men. Until recently, it was the leading cancer among men aged 15-29, and it is now second only to the AIDS-related neoplasm, Kaposi's sarcoma. Although survival has improved, young men still die from this neoplasm, and many survivors live most of their adult years with very undesirable consequences of their disease. The steady rise in incidence of this group of tumors needs to be explained, and is made all the more alarming by the possibility that the set of factors responsible for increasing incidence rates of testicular cancer may also be causing a poorly measured increase in the prevalence of various urogenital malformations in male infants. The two established risk factors are family history of testis cancer (relative risk of 10 for brothers) and a personal history of cryptorchidism or congenitally undescended testicles (relative risk 2.5-18). Familial risk, segregation analysis and preliminary linkage analyses suggest that major susceptibility genes predispose to testis cancer and possibly to the antecedent condition cryptorchidism. Linkage analysis of 180 families conducted by the International Testis Cancer Linkage Consortium (ITCLC) identified a region of Xq27 with significant evidence for linkage, with a pattern of occurrence suggesting that a gene in the region, TGCT1, confers risk of both testis cancer and cryptorchidism. We have identified and partially enrolled a population- based sample of 301 multiple case families informative for genetic linkage analysis of testis cancer and cryptorchidism. To search for major susceptibility genes, we propose to complete enrollment of a full set of 497 such families; contribute to the ongoing effort to clone TGCT; and conduct a two-stage genome scan among this series of 497 families in which we will collaborate with the ITCLC both to identify regions to be studied in the second, fine mapping stage, and to implement fine mapping efforts. The 497 enrolled families will be the largest set of informative families assembled, and this research should substantially accelerate discovery of genes predisposing to these conditions. Because this is a population-based study, the resource assembled in the proposed research will be appropriate for immediate gene characterization upon identification and cloning of major susceptibility genes for these conditions.

描述（由申请人提供）：睾丸癌是一种非常年轻男性的疾病。直到最近，它还是 15-29 岁男性中的首要癌症，现在仅次于与艾滋病相关的肿瘤——卡波西肉瘤。尽管生存率有所提高，但年轻人仍然死于这种肿瘤，许多幸存者在成年后的大部分时间里都承受着疾病带来的非常不良的后果。这类肿瘤发病率的稳步上升需要得到解释，并且更令人震惊的是，导致睾丸癌发病率增加的一系列因素也可能导致男婴中各种泌尿生殖畸形患病率的增加，而这种增加的测量不准确。两个已确定的风险因素是睾丸癌家族史（兄弟的相对风险为 10）和隐睾或先天性睾丸未降的个人史（相对风险为 2.5-18）。家族风险、分离分析和初步连锁分析表明，主要易感基因易患睾丸癌，并可能易患隐睾症。国际睾丸癌连锁联盟 (ITCLC) 对 180 个家族进行连锁分析，确定了 Xq27 的一个区域，该区域具有重要的连锁证据，其发生模式表明该区域的基因 TGCT1 会导致睾丸癌和隐睾的风险。我们已经确定并部分纳入了 301 个多病例家庭的基于人群的样本，为睾丸癌和隐睾的遗传连锁分析提供了信息。为寻找主要易感基因，拟完成497个此类家庭的全套入组；为克隆 TGCT 的持续努力做出贡献；并在这一系列 497 个家族中进行两阶段基因组扫描，其中我们将与 ITCLC 合作，以确定在第二个精细绘图阶段要研究的区域，并实施精细绘图工作。 497 个登记家庭将是最大的信息丰富的家庭集合，这项研究将大大加速发现易患这些疾病的基因。由于这是一项基于人群的研究，因此拟议研究中汇集的资源将适合在识别和克隆这些病症的主要易感基因后立即进行基因表征。