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. Project Narrative 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA140360-06
Application #
8721346
Study Section
Subcommittee B - Comprehensiveness (NCI)
Program Officer
Perkins, Susan N
Project Start
2010-09-01
Project End
2015-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
Peckham-Gregory, Erin C; Thapa, Dharma R; Martinson, Jeremy et al. (2016) MicroRNA-related polymorphisms and non-Hodgkin lymphoma susceptibility in the Multicenter AIDS Cohort Study. Cancer Epidemiol 45:47-57
Hussain, Shehnaz K; Makgoeng, Solomon B; Everly, Matthew J et al. (2016) HLA and Risk of Diffuse Large B cell Lymphoma After Solid Organ Transplantation. Transplantation 100:2453-2460
Thapa, Dharma R; Hussain, Shehnaz K; Tran, Wen-Ching et al. (2014) Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL. J Acquir Immune Defic Syndr 66:229-37
Chang, Po-Yin; Detels, Roger; Martínez-Maza, Otoniel et al. (2014) Comment on ""characteristics of B-cell lymphomas in HIV/HCV-coinfected patients during the combined antiretroviral therapy era: an ANRS CO16 LYMPHOVIR cohort study"". J Acquir Immune Defic Syndr 67:e84-6
Vendrame, Elena; Hussain, Shehnaz K; Breen, Elizabeth Crabb et al. (2014) Serum levels of cytokines and biomarkers for inflammation and immune activation, and HIV-associated non-Hodgkin B-cell lymphoma risk. Cancer Epidemiol Biomarkers Prev 23:343-9
Wiley, Dorothy J; Li, Xiuhong; Hsu, Hilary et al. (2013) Factors affecting the prevalence of strongly and weakly carcinogenic and lower-risk human papillomaviruses in anal specimens in a cohort of men who have sex with men (MSM). PLoS One 8:e79492
Hussain, Shehnaz K; Zhu, Weiming; Chang, Shen-Chih et al. (2013) Serum levels of the chemokine CXCL13, genetic variation in CXCL13 and its receptor CXCR5, and HIV-associated non-hodgkin B-cell lymphoma risk. Cancer Epidemiol Biomarkers Prev 22:295-307
Clarke, C A; Morton, L M; Lynch, C et al. (2013) Risk of lymphoma subtypes after solid organ transplantation in the United States. Br J Cancer 109:280-8
Hussain, Shehnaz K; Hessol, Nancy A; Levine, Alexandra M et al. (2013) Serum biomarkers of immune activation and subsequent risk of non-hodgkin B-cell lymphoma among HIV-infected women. Cancer Epidemiol Biomarkers Prev 22:2084-93
Nicholaou, Matthew J; Martinson, Jeremy J; Abraham, Alison G et al. (2013) HAART-associated dyslipidemia varies by biogeographical ancestry in the multicenter AIDS cohort study. AIDS Res Hum Retroviruses 29:871-9

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