The goals of this career development plan are to develop expertise in the area of molecular epidemiology and initiate an independent research career focused on population based study of genetic susceptibility to lung cancer. This plan includes didactic coursework in epidemiology through the University of New Mexico's Master's in Public Health program, hands on training in expert epidemiology and molecular biology laboratories, mentorship from an advisory committee, and a molecular epidemiology based research agenda. The goal of the proposed research is to examine the association of folate gene polymorphisms, dietary folate intake, and folate gene expression changes with lung cancer predictive promoter methylation patterns. The following 8 genes are analyzed for promoter methylation in the sputum of smokers: p16, MGMT, RASSF1A, DAPK, GATA5 and GATA4, PAX5( and PAX5(. Smokers that have 3 or more methylated gene promoters from a panel of these eight genes have a 6.5 fold greater risk to develop lung cancer compared to smokers with 0 methylated gene promoters. Thus, smokers with 3 or more methylated gene promoters assayed from this panel are defined as cases for this study and smokers with 0 methylated genes are defined as controls. Cases and controls come from high risk smoking cohorts from the Lovelace Respiratory Research Institute and the Albuquerque Veterans Affairs Medical Center in Albuquerque, New Mexico. Extensive data are collected for these cohorts including sputum, blood, spirometry, Harvard Food Frequency questionnaire data, and American Thoracic Society respiratory questionnaire data. The proposed training and research agenda in this proposal will draw upon and strengthen the candidate's skills in molecular biology and further develop her skills in population based research and epidemiology. The research agenda of this plan will contribute to a greater understanding of the genetic and environmental factors involved in the development of lung cancer and foster further research questions about the role of environment and genetic susceptibility for lung cancer prevention and treatment.
|Flores, Kristina G; Stidley, Christine A; Mackey, Amanda J et al. (2012) Sex-specific association of sequence variants in CBS and MTRR with risk for promoter hypermethylation in the lung epithelium of smokers. Carcinogenesis 33:1542-7|
|Leng, Shuguang; Bernauer, Amanda M; Hong, Chibo et al. (2011) The A/G allele of rs16906252 predicts for MGMT methylation and is selectively silenced in premalignant lesions from smokers and in lung adenocarcinomas. Clin Cancer Res 17:2014-23|