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Grant Details

Grant Number: 5R03CA113240-02 Interpret this number
Primary Investigator: Yao, Yin
Organization: Johns Hopkins University
Project Title: Gene-Gene Interaction in Nasopharyngeal Carcinoma
Fiscal Year: 2005
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Abstract

DESCRIPTION (provided by applicant): Nasopharyngeal carcinoma (NPC) has a multi-factorial etiology with risk determined by a combination of genetic and environmental factors. There is evidence of a genetic predisposition to NPC, but several environmental exposures also contribute to disease risk. These environmental factors include intake of preserved food containing nitrosamines and nitrite, cigarette smoking, and infection with Epstein-Barr Virus (EBV). We are proposing a population based study in a high-risk area in China to consider each of these risk factors related to food intake and smoking status alone and in combination with polymorphism in 10 metabolic polymorphisms. Specifically, we will examine whether these polymorphisms that result in a deficiency in the production, stability and function of 5 CYP genes (CYP1A1, CYP1A2, CYP2D6, CYP2E1, CYP1B1) and a few other polymorphisms (GSTM1, GSTT1, NQO1, NAT1 and NAT2) contribute to the development of NPC and to test for the interaction with high risk genotypes and modifiable risk factors including smoking, consumption of salted fish and perserved fruits and vegetables. Newly developed statistical methods will be applied to assess interaction(s) among 10 relevant genes using cases and controls from a relatively homogenous population. In particular, we will collect 500 cases and 500 friend controls who will match cases by age (frequency matching) and by gender to perform a epidemiologic investigation and genetic polymorphism studies. This study builds upon a long-term collaboration between Johns Hopkins University and the Cancer Center of Sun Yat-Sen University (CCSYSY) in Guangzhou, China. Dr. Yao, PI, has been collaborating with a research group at CCSYSU in this Chinese population and recently reported evidence of linkage to chromosome 4 from a genome-wide search for susceptibility gene.

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Publications

Pretreatment levels of peripheral neutrophils and lymphocytes as independent prognostic factors in patients with nasopharyngeal carcinoma.
Authors: He J.R. , Shen G.P. , Ren Z.F. , Qin H. , Cui C. , Zhang Y. , Zeng Y.X. , Jia W.H. .
Source: Head & neck, 2012 Dec; 34(12), p. 1769-76.
EPub date: 2012-02-09.
PMID: 22318781
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Comprehensive pathway-based association study of DNA repair gene variants and the risk of nasopharyngeal carcinoma.
Authors: Qin H.D. , Shugart Y.Y. , Bei J.X. , Pan Q.H. , Chen L. , Feng Q.S. , Chen L.Z. , Huang W. , Liu J.J. , Jorgensen T.J. , et al. .
Source: Cancer research, 2011-04-15; 71(8), p. 3000-8.
EPub date: 2011-03-02.
PMID: 21368091
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Effect of family history of cancers and environmental factors on risk of nasopharyngeal carcinoma in Guangdong, China.
Authors: Ren Z.F. , Liu W.S. , Qin H.D. , Xu Y.F. , Yu D.D. , Feng Q.S. , Chen L.Z. , Shu X.O. , Zeng Y.X. , Jia W.H. .
Source: Cancer epidemiology, 2010 Aug; 34(4), p. 419-24.
EPub date: 2010-05-12.
PMID: 20462827
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A case-control and a family-based association study revealing an association between CYP2E1 polymorphisms and nasopharyngeal carcinoma risk in Cantonese.
Authors: Jia W.H. , Pan Q.H. , Qin H.D. , Xu Y.F. , Shen G.P. , Chen L. , Chen L.Z. , Feng Q.S. , Hong M.H. , Zeng Y.X. , et al. .
Source: Carcinogenesis, 2009 Dec; 30(12), p. 2031-6.
PMID: 19805575
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Sequence variants in toll-like receptor 10 are associated with nasopharyngeal carcinoma risk.
Authors: Zhou X.X. , Jia W.H. , Shen G.P. , Qin H.D. , Yu X.J. , Chen L.Z. , Feng Q.S. , Shugart Y.Y. , Zeng Y.X. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2006 May; 15(5), p. 862-6.
PMID: 16702361
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Application of family-based association testing to assess the genotype-phenotype association involved in complex traits using single-nucleotide polymorphisms.
Authors: Wang M.H. , Guo M. , Shugart Y.Y. .
Source: BMC genetics, 2005-12-30; 6 Suppl 1, p. S68.
EPub date: 2005-12-30.
PMID: 16451681
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Application of the propensity score in a covariate-based linkage analysis of the Collaborative Study on the Genetics of Alcoholism.
Authors: Doan B.Q. , Frangakis C.E. , Shugart Y.Y. , Bailey-Wilson J.E. .
Source: BMC genetics, 2005-12-30; 6 Suppl 1, p. S33.
EPub date: 2005-12-30.
PMID: 16451643
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