Evaluation of the Role of Cytomegalovirus Infection in the Development of Acute Lymphoblastic Leukemia and Other Cancers

Abstract

Acute lymphoblastic leukemia (ALL) is the most prevalent pediatric malignancy, and a leading cause of death in children. Understanding the risk factors of pediatric ALL is necessary to enable early detection and prevention. Congenital cytomegalovirus (cCMV) has recently been identified as a possible risk factor of ALL. In Manuscript 1, we compared the prevalence of cCMV infection in newborn dried blood spots of ALL cases and cancer-free controls. There was no difference in the odds of cCMV infection comparing ALL cases to controls in our primary analysis. However, cCMV was significantly more prevalent among hyperdiploid ALL cases compared to unmatched controls. These findings offer partial support for the association of cCMV with ALL.CMV is among the most common viral infections following solid organ transplantation (SOT). CMV disease post-SOT has been associated with an increased risk of subsequent non-Hodgkin lymphoma but has not been well-studied for other hematologic malignancies. In Manuscript 2, we aimed to describe CMV infection status pre-transplant as it relates to the incidence of leukemias, lymphomas, and myeloma. We identified that CMV recipient and donor sero-mismatch (R-/D+) was associated with significantly lower risk of diffuse large B-cell lymphoma compared to CMV seronegative R/D pairs, indicating CMV may have a protective role in carcinogenesis. Lastly, in Manuscript 3, we leveraged the same dataset as Manuscript 2 to examine associations of CMV with solid tumor cancer risk among SOT recipients. Using linked data from the United States SOT registry and 32 cancer registries, we report an inverse association between R-/D+ CMV serostatus and small intestine cancer, and a positive association between CMV R+ serostatus and lung cancer. CMV status was not associated with risk for other cancers. Findings from this dissertation may motivate and inform future work to further understand the relationship between this highly prevalent virus and cancer.