Lauren Teras

Ph.D

American Cancer Society

Senior Scientific Director

PLCO (Learn more about this study)

2019-0020

Jun 28, 2019

Infectious risk factors for non-Hodgkin and myeloid malignancies: a pooled analysis of prospective studies

Hematologic cancers are collectively the 3rd most common cancer (176,200 new cases expected in 2019) and the 2nd most common cause of cancer death (56,770 deaths expected in 2019), yet there are currently no approved screening or early detection tools for these cancers. Incidence of hematologic cancers rose dramatically over the last half of the 20th century; and continue to rise for some of the most common subtypes. Despite improvements, 5-year survival remains <50% for several hematologic cancer subtypes, and ten-year survival <25%. Further, hematologic cancers are among the most expensive cancer to treat, and these costs continue to increase exponentially with newer therapy options. Despite the incidence, mortality, and financial burden of these cancers, very little is known about their etiology. The short list of well-established risk factors includes severe immune dysregulation, and select infectious agents (with very rare types of lymphoma or leukemia). A longer list of infectious agents has been implicated in the etiology of these cancers (including associations with more common types of hematologic cancer), but methodological issues, predominantly small sample size in individual studies, have made it difficult to confirm these hypothesized associations. Furthermore, many risk factors for hematologic cancers vary by subtype, and large studies are needed to explore etiologic heterogeneity. Opportunities for the primary prevention of cancer are not always evident, but infectious causes of cancer allow for possible interventions through treatment of the infection, prophylaxis, and/or vaccination. Furthermore, understanding associations with infectious exposures can help elucidate the biology of these cancers and how best to intervene. We propose to conduct a large, pooled analysis to investigate hypothesized associations of infectious antibodies with two groups of the most common hematologic malignancies– non-Hodgkin lymphomas and myeloid malignancies. Of note we will not include Hodgkin lymphomas or plasma cell neoplasms in this study. The former because of the age distribution of the cohorts and resulting small number of cases. The latter because of concerns about subclinical disease effects (reverse causality) with our exposure measure being the product of plasma cells (antibodies). The proposed study will contribute important insights into the role of infectious exposures, and related underlying mechanisms, for the etiology, and etiologic heterogeneity, of a group of understudied malignancies with considerable morbidity, mortality, and public health impact.

Primary Aim:
Aim 1: Identify associations of circulating antibodies to infectious agents with risk of non-Hodgkin lymphoma (NHL) and NHL subtypes including diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Aim 2: Identify associations of circulating antibodies to infectious agents with risk of myeloid malignancies and myeloid malignancy subtypes including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myeloid leukemia (CML).

Hodgkin lymphomas and plasma cell neoplasms are not included in this study because of sample size (Hodgkin) and concerns about reverse causality (plasma cell neoplasms). We hope to include additional subtypes including T-cell lymphomas, marginal zone lymphoma, mantle cell lymphoma, and Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma as sample size in the pooled cohort allows.