Biography

Dr. Wang received a B.S. in biology from the Massachusetts Institute of Technology and a Ph.D. in epidemiology from The Johns Hopkins Bloomberg School of Public Health. From 1998 to 2000, she served as an Epidemic Intelligence Service Officer at the Centers for Disease Control and Prevention. Dr. Wang joined the NCI in 2000 as an investigator and was tenured in 2008. Her research focus includes understanding the molecular pathogenesis and genetic susceptibility of cervical cancer and non-Hodgkin lymphoma.

Research Interests

Genetic Susceptibility and Molecular Markers of Cancer Pathogenesis

We are conducting molecular epidemiology studies to identify genetic markers of susceptibility in the exposure-to-disease continuum, as well as biomarkers of cancer development and progression in two tumor systems: cervical neoplasia and non-Hodgkin's lymphoma. For both tumors, ongoing studies include investigations of markers of susceptibility with particular emphasis on immune and immune-related genes. In addition, identifying molecular markers of disease pathogenesis are underway utilizing novel biological methods, including cytogenetic techniques, gene expression via microarray technologies, and restriction landmark genome scanning.

Genetics of Cervical Neoplasia

Susceptibility Genes for HPV Infection and Cervical Cancer

While infection by human papillomavirus (HPV) is accepted as the central risk factor for cervical cancer, it is unlikely to be sufficient for developing cancer. Only a subset of HPV-infected individuals develop persistent infection, and of those, a subset develop low-grade lesions, and fewer develop high-grade lesions and subsequent cancer. These findings indicate that factors in addition to HPV infection are likely to be important determinants in cervical cancer carcinogenesis. Ongoing research includes investigating the role of specific genetic factors in determining HPV-persistence and subsequent progression of disease. Since genetic factors may modify HPV infection, our research includes efforts aimed at assessing genes that influence immune function. In three NCI-sponsored studies, including a population-based cohort of 10,000 women in Costa Rica, a population-based cohort of 24,000 women in Portland, Oregon, and a case-control study in the Eastern United States, we are examining the association between various polymorphic genes important to immune function, such as killer immunoglobulin receptors (KIRs) with cervical cancer. To enhance the number of cervical cancer cases and thus power for our genetic susceptibility studies, we have now completed the Genetic Supplementation Study (GSS) within the Guanaste Study. Also planned within the on-going HPV vaccine efficacy trial in Costa Rica are studies to assess the role of genetic factors in the heterogeneity of vaccine responses and in rapid onset disease.

Biomarkers of Risk for Progressive Cervical Neoplasia

To increase our understanding of the mechanisms involved in cervical carcinogenesis and to develop a new set of biomarkers that can distinguish those at highest risk of cervical cancer from those with benign infection, the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) was launched in November 2002 to comprehensively assesses biomarkers of risk for progressive cervical neoplasia. Employing an epidemiologic study design, we plan to identify, validate, and quantify the risk relationships of candidate biomarkers in cervical carcinogenesis. We are developing a comprehensive list of potential risk biomarkers via gene expression and microarray technology. By measuring gene expression profiles, we will gain a comprehensive in vivo picture of cervical neoplasia carcinogenesis. Candidate biomarkers will subsequently be validated for key outcomes related to progression or non-progression.

Genetics of Non-Hodgkin's Lymphoma

Susceptibility Genes for Non-Hodgkin's Lymphoma

We are currently evaluating the role of genetic polymorphisms in non-Hodgkin's lymphoma (NHL) susceptibility in the NCI-sponsored NHL multi-center case-control study in the United States (U.S.). While the major risk factors for NHL are not yet known, studies have consistently shown a strong relationship between factors that alter the immune system and NHL. We are therefore investigating candidate genes that are relevant to immune pathways hypothesized to play a role in NHL etiology. These include: (1) inflammatory and regulatory cytokines, (2) Th1/Th2 cytokines, (3) genes involved in innate immunity, and (4) chemokines. We are also investigating candidate genes hypothesized to influence NHL survival.

Keywords

• Molecular epidemiology, molecular pathology, genetic susceptibility, cervical neoplasia, human papillomavirus, non-Hodgkin lymphoma

Selected Publications

• Wang SS, Cerhan JR, Hartge P, Davis S, Cozen W, Severson R, Chatterjee N, Yeager M, Chanock S, Rothman N. Common genetic variants in pro-inflammatory and other immunoregulatory genes and the risk for non-Hodgkin lymphoma. Cancer Res 2006;66:9771-80.
• Wang SS, Davis S, Cerhan JR, Hartge P, Severson RK, Cozen W, Lan Q, Welch R, Chanock SJ, Rothman N. Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma. Carcinogenesis 2006;27:1828-34.
• Wang SS, Sherman ME, Silverberg SG, Carreon JD, Lacey JV Jr, Zaino R, Kurman RJ, Hildesheim A. Pathological characteristics of cervical adenocarcinoma in a multi-center U.S.-based study. Gynecol Oncol 2006;103:541-46.
• Morton LM, Schenk M, Hein DW, Davis S, Zahm SH, Cozen W, Cerhan JR, Hartge P, Welch R, Chanock SJ, Rothman N, Wang SS. Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma. Pharmacogenet Genomics 2006;16:537-45.
• Wang SS, Cozen W, Severson RK, Hartge P, Cerhan JR, Davis S, Welch R, Rothman N, Chanock SJ. Cyclin D1 splice variant and risk for non-Hodgkin lymphoma (NHL). Hum Genet 2006;120:297-300.
• Cerhan JR, Wang S, Maurer MJ, Ansell SM, Geyer SM, Cozen W, Morton LM, Davis S, Severson RK, Rothman N, Lynch CF, Wacholder S, Chanock SJ, Habermann TM, Hartge P. Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival. Blood 2007;109:5439-46.
• Wang SS, Slager S, Brennan P, Holly EA, De Sanjose S, Bernstein L, Boffetta P, Cerhan JR, Chiu BC, Cocco P, Mensah F, Bracci P, Seniori Costantini A, Maynadie M, Zhang Y, Nieters A, Spinelli J, Severson RK, Cozen W, Roman E, Dal Maso L, Weisenberger D, Franceschi S, Davis S, La Vecchia C, Foretova L, Becker N, Staines A, Vornanen M, Zheng T, Hartge P. Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10,211 cases and 11,905 controls from the International Lymphoma Epidemiology Consortium (InterLymph). Blood 2007;109:3479-88.
• Purdue MP, Hartge P, Davis S, Cerhan JR, Colt JS, Cozen W, Severson RK, Li Y, Chanock SJ, Rothman N, Wang SS. Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma. Cancer Causes Control 2007 18:989-99.
• Wang SS, Cozen W, Cerhan J, Colt J, Morton LM, De Roos A, Engels EA, Severson RK, Rothman N, Hartge P. Immune mechanisms in non-Hodgkin lymphoma: joint effects of the TNF G308A and IL10 T3575A polymorphisms with non-Hodgkin lymphoma risk factors. Cancer Res 2007;67:5042-54.
• Shivapurkar N, Sherman ME, Stastny V, Echebiri C, Rader JS, Nayar R, Bonfiglio TA, Gazdar AF, Wang SS. Evaluation of candidate methylation markers to detect cervical neoplasia. Gynecol Onc 2007;107:549-53.
• Wang SS, Smiraglia DJ, Wu YZ, Ghosh S, Rader JS, Cho KR, Plass C, Sherman ME. Identification of novel methylation markers in cervical cancer using restriction landmark genomic scanning (RLGS). Cancer Res 2008;68(7):2489-97.
• Wang SS, Davis S, Hartge P, Cozen W, Severson RK, Cerhan JR, Rothman N. Chromosomal aberrations in peripheral blood lymphocytes and risk for non-Hodgkin lymphoma. J Natl Cancer Inst 2008;39:78-82.
• Carreon JD, Morton LM, Devesa SS, Clarke-Dur C, Gomez S, Glaser S, Linet MS, Sakoda LC, Wang SS. Incidence of lymphoid neoplasms by subtype among six Asian ethnic groups in the United States, 1996-2004. Cancer Causes Control 2008;19(10):1171-81.
• Wentzensen N, Schiffman M, Dunn ST, Zuna RE, Gold MA, Wacholder S, Allan RA, Walker J, Wang SS. Human papillomavirus (HPV) type distribution by disease progression in the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED). Int J Cancer 2008;Sep 2 (E-pub).
• Wang SS, Maurer MJ, Morton LM, Habermann TM, Lynch CF, Cozen W, Davis S, Severson RK, Rothman N, Chanock SJ, Hartge P, Cerhan JR. Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. Leukemia 2008; Oct 2 (E-pub).
• Wang SS, Rodriguez AC, Herrero R, Burk RD, Porras C, Gonzalez P, Sherman ME, Wacholder S, Lan ZE, Welch R, Schiffman M, Chanock SJ, Hildesheim A. Common genetic variants and risk for HPV persistence and progression to cervical cancer. J Infect Dis 2008; Nov 14 (E-pub).
• Purdue MP, Lan Q, Wang SS, Kricker A, Menashe I, Zheng T, Hartge P, Grulich A, Zhang Y, Morton LM, Vajdic C, Holford TR, Severson RK, Leaderer B, Cerhan JR, Yeager M, Cozen W, Yeager M, Cozen W, Jacobs K, Davis S, Rothman N, Chanock SJ, Chatterjee N, Armstrong B. A pooled investigation of toll-like receptor gene variants and risk of non-Hodgkin lymphoma. Carcinogenesis 2008;Nov 24 (E-pub).
• Wentzensen N, Sherman M, Schiffman M, Wang SS. Utility of methylation markers in cervical cancer screening: appraisal of the state-of-the-science. Gynecol Oncol 2008; Dec 1 (E-pub).
• Wang SS, Zuna RE, Wentzensen N, Gold MA, Dunn ST, Wacholder S, Allan RA, Safaeian M, Sakoda L, Schiffman M, Walker J. Human papillomavirus (HPV) cofactors by disease progression and HPV types in the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED). Cancer Epidemiol Biomarkers Prev (In Press)
• Colt JS, Rothman N, Severson RK, Hartge P, Cerhan JR, Chatterjee N, Cozen W, Morton LM, De Roos AJ, Davis S, Chanock S, Wang SS. Exposure to organochlorines, genetic variation in immune function genes, and risk of non-Hodgkin lymphoma. Blood (In Press)

Collaborators

DCEG Collaborators

• Stephen Chanock, M.D., Nilanjan Chatterjee, Ph.D., Susan Devesa, Sc.D., Patricia Hartge, Sc.D., Allan Hildesheim, Ph.D., Qing Lan, M.D., M.P.H., Martha Linet, M.D.,M.P.H, Lindsay Morton, Ph.D., Nathaniel Rothman, M.D., M.H.S., Mahboobeh Safaiean, Ph.D., Mark Schiffman, M.D., M.P.H., Mark Sherman, M.D., Sholom Wacholder, Ph.D., Nicolas Wentzensen, M.D., M.S.,Ph.D., Kai Yu, Ph.D.

Other NCI Collaborators

• Mary Carrington, Ph.D.

Other Scientific Collaborators

• Paul Ahlquist, Ph.D., The University of Wisconsin at Madison, Madison, WI
• James Cerhan, M.D., Ph.D., Mayo Clinic, Rochester, MN
• Terence Dunn, Ph.D., Oklahoma University Health Sciences Center, Oklahoma City, OK
• Michael Gold, M.D., Oklahoma University Health Sciences Center, Oklahoma City, OK
• Patti E. Gravitt, Ph.D., M.S., The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
• Rolando Herrero, M.D., Ministry of Health, San Jose, Costa Rica
• Paul Lambert, Ph.D., The University of Wisconsin at Madison, Madison, WI
• Michael Newton, Ph.D., The University of Wisconsin at Madison, Madison, WI
• Joan Walker, M.D., Oklahoma University Health Sciences Center, Oklahoma City, OK
• Rosemary Zuna, M.D., Oklahoma University Health Sciences Center, Oklahoma City, OK