Molecular Epidemiology of B cell Activation, DNA Repair & HIV-Associated Lymphoma

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DESCRIPTION (provided by applicant): This proposal describes a five-year program designed in the short-term to provide additional specific training and mentored research experience to Dr. Shehnaz K. Hussain to enable her to achieve her long-term goal of successfully launching a career as an independent academic researcher and scientist in cancer molecular epidemiology with a focus on infection-related cancers. Dr. Hussain received a Sc.M. in epidemiology from Johns Hopkins, a Ph.D. in epidemiology from U. W. Seattle, was a postdoc at the Karolinska Institute, and is currently a newly appointed Assistant Professor in the UCLA Department of Epidemiology. Dr. Hussain will meet her academic career goals with the help of a highly experienced and supportive interdisciplinary team of mentors including Drs. Zhang (cancer molecular epidemiology), Martinez-Maza (cancer immunology), Detels (HIV/AIDS epidemiology), and Sinsheimer (statistical genetics); a clear and directed career development plan including grant and manuscript writing, didactic training in computational biology, bioinformatics, complex data analysis, and issues in the design/conduct of genome wide association studies, and wet-lab training; a strong and collaborative institutional environment consisting of multiple centers, departments, and schools of UCLA; and a well-defined research project with a high possibility of being developed into an independent research program. The main hypothesis of Dr. Hussain's research project is that adverse genotypes of B cell activation-related genes will be associated with increased risk of HIV-associated non-Hodgkin's lymphoma (AIDS-NHL). Dr. Hussain will conduct a nested case-control study in two well-described HIV cohorts, the MACS and WIHS. TagSNPs in candidate genes, prioritized by putative functionality, will be genotyped in AIDS-NHL cases and matched controls. Multivariate logistic regression models and pathway-based statistical methods will be utilized to determine the association between tagSNPs and haplotypes and AIDS-NHL risk, and to examine whether these associations are modified by other genetic, molecular, or epidemiological factors. This project will integrate high-throughput technologies, innovative statistical methods, and a wealth of previously collected data to extend our understanding of NHL etiology. PUBLIC HEALTH RELEVANCE: Non-Hodgkin's lymphoma (NHL) poses an important public health burden in the U.S., which is underscored by the steady rise in incidence and mortality and high number of average years of life lost. Unfortunately, the exact causes of NHL are still largely unknown. Etiological studies of NHL in HIV infected individuals, who are at very high risk of NHL, will inform future strategies for risk assessment, detection, and prevention of NHL.