Renal cancer genomic alterations and environmental risk(RMI)

肾癌基因组改变和环境风险（RMI）

• 批准号: 7236224
• 负责人: Frederic M. Waldman
• 金额: $ 27.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7236224
• 关键词: Aromatic Polycyclic Hydrocarbons; Asbestos; Cancer Patient; Clear Cell; Clinical; DNA; DNA amplification; Diagnostic Neoplasm Staging; Environmental Risk Factor; Environmental and Occupational Exposure; European; Formalin; Freezing; Genes; Genetic; Genomics; Heavy Metals; Histologic; Hypertension; Incidence; International; Kidney Neoplasms; Life Style; Malignant Neoplasms; Malignant neoplasm of kidney; National Cancer Institute; Numbers; Obesity; Occupational; Occupational Exposure; Patients; Petroleum; Rain; Recording of previous events; Renal Cell Carcinoma; Renal carcinoma; Renal function; Research; Research Design; Risk Factors; Smoking; Staging; Statistically Significant; Tissue Microarray; Tissues; Trichloroethylene; Tumor Subtype; Tumor Tissue; Tumor stage; United States; base; cancer genomics; cancer risk; case control; cohort; genetic risk factor; size; tumor

DESCRIPTION (provided by applicant): A number of environmental, occupational and life style factors have been associated with renal cell cancer (RCC) incidence. However, the mechanism by which these risk factors cause RCC, presumably acting through alteration of specific genes, is unknown. We hypothesize that specific genomic alterations detected in renal cancers (DNA gain or loss) are associated with renal cancer risk factors. We propose to analyze associations between risk factors and genomic alterations in renal tumors collected as part of the Eastern European Renal Cell Cancer Study (EERCC), being carried out by the National Cancer Institute and the International Association for Research on Cancer (IARC). We hypothesize that specific qenomic alterations in renal cancers (DNA gain or loss) are associated with renal cancer risk factors and with tumor proqression. Our Aims are: The overall design of this study is to characterize over 700 renal tumors by array CGH to define genomic alterations and their associations with clinical variables, and with exposure, and genetic risk factors. 1. Identify genomic alterations associated with tumor stage in conventional (clear cell) renal cancer. Array based CGH will be used to define copy number gains and losses, including DNA amplifications and homozygous deletions, in DNA from 200 conventional RCC grouped according to stage (I-IV). 2. Identify associations of genomic alterations with statistically significant exposure, occupational, and genetic risk factors defined using this IARC case-control cohort of renal cancer patients. 500 additional tumors will be characterized by array CGH beyond those studied in Aim 1. Patients will be selected based on their exposure history, to generate the most power for analysis (enriching for highest exposure groups). Risk factors to be considered include smoking, occupational, and environmental exposures (trichloroethylene, polycyclic aromatic hydrocarbons, petroleum products, asbestos, and heavy metals) and factors that alter renal function (obesity and hypertension). 3. Validate genes identified in Aims 1 and 2 using immunohistochemical analysis of renal tumor tissue microarrays containing the entire cohort of tumors.

描述（由申请人提供）：许多环境、职业和生活方式因素与肾细胞癌（RCC）的发病率有关。然而，这些风险因素导致RCC的机制，可能是通过改变特定的基因，是未知的。我们假设在肾癌中检测到的特定基因组改变（DNA的增加或减少）与肾癌的危险因素有关。我们建议分析作为国家癌症研究所和国际癌症研究协会（IARC）开展的东欧肾细胞癌研究（EERCC）的一部分收集的肾肿瘤危险因素与基因组改变之间的关系。我们假设肾癌中特定的基因组改变（DNA的增加或减少）与肾癌的危险因素和肿瘤的进展有关。我们的目标是：

项目成果

Von Hippel-Lindau (VHL) inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors.

• DOI: 10.1371/journal.pgen.1002312
• 发表时间: 2011-10
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Moore LE;Nickerson ML;Brennan P;Toro JR;Jaeger E;Rinsky J;Han SS;Zaridze D;Matveev V;Janout V;Kollarova H;Bencko V;Navratilova M;Szeszenia-Dabrowska N;Mates D;Schmidt LS;Lenz P;Karami S;Linehan WM;Merino M;Chanock S;Boffetta P;Chow WH;Waldman FM;Rothman N
• 通讯作者: Rothman N

TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe.

• DOI: 10.1016/j.canlet.2009.11.024
• 发表时间: 2010-07
• 期刊: Cancer letters
• 影响因子: 9.7
• 作者: Katarzyna Szymańska;L. E. Moore;Nathanial Rothman;Wong-Ho Chow;Frederic M. Waldman;Erich B. Jaeger;T. Waterboer;L. Foretova;M. Navratilova;V. Janout;H. Kollárová;D. Zaridze;Vsevolod Matveev;D. Mates;N. szeszenia-Dabrowska;I. Holcatova;V. Bencko;F. Calvez-Kelm;S. Villar;M. Pawlita;Paolo Boffetta;Pierre Hainaut;P. Brennan

Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors.

• DOI: 10.1158/1078-0432.ccr-07-4921
• 发表时间: 2008-08-01
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Nickerson, Michael L.;Jaeger, Erich;Shi, Yangu;Durocher, Jeffrey A.;Mahurkar, Sunil;Zaridze, David;Matveev, Vsevolod;Janout, Vladimir;Kollarova, Hellena;Bencko, Vladimir;Navratilova, Marie;Szeszenia-Dabrowska, Neonilia;Mates, Dana;Mukeria, Anush;Holcatova, Ivana;Schmidt, Laura S.;Toro, Jorge R.;Karami, Sara;Hung, Rayjean;Gerard, Gary F.;Linehan, W. Marston;Merino, Maria;Zbar, Berton;Boffetta, Paolo;Brennan, Paul;Rothman, Nathaniel;Chow, Wong-Ho;Waldman, Frederic M.;Moore, Lee E.
• 通讯作者: Moore, Lee E.