It is becoming increasingly evident that the etiology of lung cancer involves a combination of both environmental and hereditary factors and that individuals may vary substantially in their genetic susceptibility to carcinogens such as tobacco. The primary goal of this project is to identify individuals genetically predisposed to be at very high risk. To do so we will establish a population-based lung cancer registry consisting of approximately 2 million. We will collect demographic, family history, and smoking data on lung cancer patients and family members. Blood samples will be collected and stored in conjunction with the SPORE Pathology Resource Core (Core B). We will perform segregation analysis on these families to fit genetic and environmental hypotheses and determine the best model characterizing familial aggregation of lung cancer (Aim 1). In doing so, we will also identify specific kindreds which will be useful for subsequent genetic linkage and candidate gene studies. Proband clinical characteristics which may be associated with increased cancer risk to family members will be determined. Sensitivity of peripheral blood lymphocyte DNA to mutagen-induced chromatid breaks will be assessed in lung cancer patients with an without a family history of lung cancer (Aim 2). In addition, we will compare patterns of allele loss in lung cancers from lung cancer patients with a family history of lung cancer and will determine if different patterns of allele loss occur in familial tumors (Aim 3). This part of the project will be closely integrated with Project #3, Molecular Markers for Early Lung Cancer Detection and Project 1, Identification of 3p Recessive Oncogenes in Lung Cancer. Moreover, this project could interact closely with Developmental Project 1 in determining patterns of potential inherited predisposition to nicotine dependency within lung cancer prone families. In addition to addressing the Specific Aims, one of the most important translational applications of this proposal will be the identification of a cohort of asymptomatic individuals who, because of a genetic predisposition, may be candidates for future development of lung cancer chemoprevention trials, a goal of Project #4, or the development of early detection strategies, a goal of Project #3.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA070907-03S1
Application #
6296133
Study Section
Project Start
1998-09-01
Project End
1999-08-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
City
Dallas
State
TX
Country
United States
Zip Code
75390
Zhang, Wei; Girard, Luc; Zhang, Yu-An et al. (2018) Small cell lung cancer tumors and preclinical models display heterogeneity of neuroendocrine phenotypes. Transl Lung Cancer Res 7:32-49
Akbay, Esra A; Kim, James (2018) Autochthonous murine models for the study of smoker and never-smoker associated lung cancers. Transl Lung Cancer Res 7:464-486
McMillan, Elizabeth A; Ryu, Myung-Jeom; Diep, Caroline H et al. (2018) Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer. Cell 173:864-878.e29
Tan, Xiaochao; Banerjee, Priyam; Liu, Xin et al. (2018) The epithelial-to-mesenchymal transition activator ZEB1 initiates a prometastatic competing endogenous RNA network. J Clin Invest 128:1267-1282
Skoulidis, Ferdinandos; Goldberg, Michael E; Greenawalt, Danielle M et al. (2018) STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma. Cancer Discov 8:822-835
Walser, Tonya C; Jing, Zhe; Tran, Linh M et al. (2018) Silencing the Snail-Dependent RNA Splice Regulator ESRP1 Drives Malignant Transformation of Human Pulmonary Epithelial Cells. Cancer Res 78:1986-1999
Ferdosi, Shadi; Rehder, Douglas S; Maranian, Paul et al. (2018) Stage Dependence, Cell-Origin Independence, and Prognostic Capacity of Serum Glycan Fucosylation, ?1-4 Branching, ?1-6 Branching, and ?2-6 Sialylation in Cancer. J Proteome Res 17:543-558
Zhou, Xiaorong; Padanad, Mahesh S; Evers, Bret M et al. (2018) Modulation of Mutant KrasG12D -Driven Lung Tumorigenesis In Vivo by Gain or Loss of PCDH7 Function. Mol Cancer Res :
Abrams, Zachary B; Zucker, Mark; Wang, Min et al. (2018) Thirty biologically interpretable clusters of transcription factors distinguish cancer type. BMC Genomics 19:738
Pietanza, M Catherine; Waqar, Saiama N; Krug, Lee M et al. (2018) Randomized, Double-Blind, Phase II Study of Temozolomide in Combination With Either Veliparib or Placebo in Patients With Relapsed-Sensitive or Refractory Small-Cell Lung Cancer. J Clin Oncol 36:2386-2394

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