My long-term goal is to become an independent molecular epidemiologist with in-depth training in genetics and advanced statistical methods in order to be able to analyzehigh throughput gene variant data to explore gene- gene and gene-environment interactions in cancer susceptibility. Mycareer development plan includedidatic courses/seminars, meetings with mentors in the areas of human genetics, cancer biology and advanced statistical methods. Myresearch proposal will focus on genetic susceptibility of blader cancer (BC). I propose to capitalize on availabilityof epidemiologicand genentic marker data from an on-going case-control study, "Markers of GeneticSusceptibilityto Bladder Cancer"(R01 CA74880,PI:Xifeng. Wu). The parent study currently include over 2,500,mostly Caucasian,BCcases and controls, matched on sex, age and ethnicity. Mygoal is to identify novel loci that confer bladder cancer susceptibility using state-of-the-art genotyping techology and novel statistical and bioinformaticstools.
The Specific Aims are: 1) To enhance my knowledge and skills in genetics and statistics to identify novel genetic loci as susceptibility markers of BC by extending the original45 potential functional SNPs to include additional 2112 tagging SNPs in genes in the DNArepair, cell cycle control and apoptotic pathways in 800 Caucasiancases and 800 Caucasiancontrols using the Illumina Golden Gate Assay;2) To assess haplotypes and diplotypes as markers of susceptibility;3) To use bioinformaticstools to assess functional significance of SNPs in the DNArepair, cell cycle control and apoptotic pathways and to correlate genotype data of DNArepair and cell cycle control with functional data derived from phenotypic assays. The secondary aim is to apply hierarchical models to refine risk assessment and to apply novel machine-learning tools to explore any gene-environment and gene-gene interactions influencing BCrisk. My project complements the parent grant in that it: 1) adds tagging SNPs to potential functional SNPs addressed in the parent grant;2) adds haplotype analyses;3) proposes novel statistical and bioinformaticsapproaches.
Bladder cancer is a tobacco-related cancer which is the fourth most common cancer in men in U.S. The fact that only a fraction of smokers develop bladder caricer indicating genetic susceptibility to the disease. This study will identify novel genetic markers may be useful as biomarkers to identify high-risk populationsthat could then be targeted for intervention programs.
|Mao, Muling; Tian, Feng; Mariadason, John M et al. (2013) Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents. Clin Cancer Res 19:657-67|
|Shu, Xiang; Lin, Jie; Wood, Christopher G et al. (2013) Energy balance, polymorphisms in the mTOR pathway, and renal cell carcinoma risk. J Natl Cancer Inst 105:424-32|
|Wang, J; Wu, X; Kamat, A et al. (2013) Fluid intake, genetic variants of UDP-glucuronosyltransferases, and bladder cancer risk. Br J Cancer 108:2372-80|
|He, Yonggang; Gong, Yilei; Lin, Jie et al. (2013) Ionizing radiation-induced Î³-H2AX activity in whole blood culture and the risk of lung cancer. Cancer Epidemiol Biomarkers Prev 22:443-51|
|Lin, Jie; Lu, Charles; Stewart, David J et al. (2012) Systematic evaluation of apoptotic pathway gene polymorphisms and lung cancer risk. Carcinogenesis 33:1699-706|
|Wen, Chi-Pang; Lin, Jie; Yang, Yi Chen et al. (2012) Hepatocellular carcinoma risk prediction model for the general population: the predictive power of transaminases. J Natl Cancer Inst 104:1599-611|
|Zhang, Xuemei; Lin, Jie; Wu, Xifeng et al. (2012) Association between GSTM1 copy number, promoter variants and susceptibility to urinary bladder cancer. Int J Mol Epidemiol Genet 3:228-36|
|Lin, Moubin; Eng, Cathy; Hawk, Ernest T et al. (2012) Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma. Cancer 118:6188-98|
|Lin, Jie; Forman, Michele R; Wang, Jianming et al. (2012) Intake of red meat and heterocyclic amines, metabolic pathway genes and bladder cancer risk. Int J Cancer 131:1892-903|
|Yin, Jikai; Lu, Charles; Gu, Jian et al. (2011) Common genetic variants in cell cycle pathway are associated with survival in stage III-IV non-small-cell lung cancer. Carcinogenesis 32:1867-71|
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