Genetic Epidemiology of Prostate Cancer

前列腺癌的遗传流行病学

• 批准号: 7393715
• 负责人: Alice Whittemore
• 金额: $ 38.53万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7393715
• 关键词: 19p; 19p13.3; Abbreviations; Accounting; African American; Alleles; Androgen Receptor; Archives; Biochemical; Biological Assay; Biotechnology; Blood; California; Cancer Family; Cancer-Predisposing Gene; Caucasians; Caucasoid Race; Chromosomes; Data; Data Analyses; Data Linkages; Databases; Distal; Expressed Sequence Tags; Family; Funding; Genes; Genetic Heterogeneity; Genetic Polymorphism; Genome; Genomics; Genotype; Hawaii; Human Genome; Individual; International; Lod Score; Los Angeles; Malignant neoplasm of prostate; Molecular; Molecular Conformation; National Cancer Institute; Northern Blotting; Numbers; Participant; Polymerase Chain Reaction; Prostate-Specific Antigen; Request for Applications; Research Institute; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Reverse Transcription; Scanning; Second Degree Relative; Signal Transduction; Single Nucleotide Polymorphism; Single-Stranded Conformational Polymorphism; Stanolone; Statistical Methods; Statistically Significant; Sweden; Testing; Tissues; Transcript; Variant; Vitamin D3 Receptor; base; cancer genetics; cancer risk; case control; cohort; gel electrophoresis; genetic epidemiology; genetic linkage analysis; genetic pedigree; genetic resource; genetic variant; genome wide association study; genome-wide linkage; member

We have obtained pedigree data, blood and archived tissue from members of 98 families containing three or more confirmed cases of prostate cancer. We have typed these families for 437 autosomal markers and have analyzed the data for linkage. Although no single chromosomal region met the genome-wide criteria for statistically significant excess allele sharing, our strongest signal on the distal end of chromosome 19p has been replicated independently by a study of multiple-case prostate cancer families in Sweden (Wiklund et al. 2003). In this competing renewal application we request funds to test the hypothesis that region 19p13.3 harbors a prostate cancer susceptibility gene. Our objectives are to: 1) narrow the region by tripling the number of markers and perform linkage analysis to exclude subregions with low lod scores, using statistical methods that accommodate both individual-specific and family-specific covariates that may account for genetic heterogeneity across families; 2a) rank the 92 known genes and 61 transcripts of unknown genes in the (narrowed) region with respect to their potential involvement in prostate cancer, and 2b) identify polymorphisms in the more promising genes; 3a) investigate associations between prostate cancer risk and the variant alleles in the identified polymorphisms by genotyping 750 African-American and 750 Caucasian case-control pairs in a casecontrol study nested within the Hawaii/Los Angeles multiethnic cohort (MEC); 3b) when warranted, investigate the functional significance of these variants. The NCI-funded International Consortium for Prostate Cancer Genetics (ICPCG) is a resource of more than 1,500 multiple-case prostate cancer families. As members of the ICPCG, our long-term aim is to pursue with this group any promising leads identified in this project.

我们从98个家庭的成员中获得了谱系数据，血液和存档组织，其中包含三个或更多已确认的前列腺癌病例。我们已经为437个常染色体标记键入这些家族，并分析了数据以进行连锁。尽管没有任何单个染色体区域符合统计上显着过多等位基因共享的全基因组的标准，但通过对瑞典的多盘前列腺癌家族的研究，我们独立地复制了我们在19p染色体远端的最强信号（Wiklund等，2003）。在此相互竞争的续签应用中，我们要求资金测试19p13.3区域的假设。我们的目标是：1）使用统计方法来排除较低LOD评分的子区域，使用统计方法来排除该区域的范围，以适应可能占家族遗传异质性的个体特异性和特异性协变量的统计方法； 2A）对（狭窄）区域中未知基因的92个已知基因和61个转录本在潜在参与前列腺癌中，而2B）识别出更有前途的基因中的多态性； 3A）研究在夏威夷/洛杉矶多族群中嵌套的Casecontrol研究中，通过基因分型对鉴定的750名非裔美国人和750种白种病例对照对在鉴定的多态性中的变异等位基因之间的关联。 3b）保证后，研究这些变体的功能意义。 NCI资助的前列腺癌遗传学（ICPCG）的国际国际财团是1,500多个多盘前列腺癌家族的资源。作为ICPCG的成员，我们的长期目标是与该小组一起追求该项目中确定的任何有希望的潜在客户。

项目成果

No evidence of linkage for chromosome 1q42.2-43 in prostate cancer.

没有证据表明前列腺癌中染色体 1q42.2-43 存在连锁。

• DOI: 10.1086/302457
• 发表时间: 1999
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: Whittemore,AS;Lin,IG;Oakley-Girvan,I;Gallagher,RP;Halpern,J;Kolonel,LN;Wu,AH;Hsieh,CL
• 通讯作者: Hsieh,CL