Abstract PR02: Glyphosate as a potential carcinogen for multiple myeloma

Abstract

Abstract Glyphosate is the most commercially successful and the most widely used herbicide in the United States and worldwide. It represents about 50% of United States herbicide usage at approximately 250 million pounds annually; the annual use of glyphosate worldwide is about 1.8 billion pounds. There has been considerable debate around the carcinogenicity of glyphosate. IARC labeled glyphosate as “probably carcinogenic to humans.” However, other agencies like the EPA have maintained that glyphosate is unlikely to pose a carcinogenic risk. In epidemiologic studies on the association of cancer and glyphosate, only multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) have a positive and statistically significant association with glyphosate. MM is a plasma cell neoplasm and the second most common hematologic malignancy in the United States. Virtually all MM cases are preceded by a precursor condition, monoclonal gammopathy of undetermined significance (MGUS). MM is regarded as a disease with environmental causes, yet its etiology and what prompts progression remain largely unclear. We employed the Vk*Myc mouse model of MM to assess the impact of glyphosate exposure on MM pathogenesis. In both wild-type and Vk*Myc mice, glyphosate induced splenomegaly and multiple peripheral blood abnormalities, including anemia and high serum IgG levels, hallmarks of MGUS and MM in humans. In Vk*Myc mice, glyphosate triggered bone lytic lesions, as well as renal damage, a phenomenon associated with human MM kidney disease. Most importantly, glyphosate upregulated Aicda, which encodes the activation-induced cytidine deaminase (AID) in the spleen and bone marrow of both wild-type and Vk*MYC mice. AID mediates somatic hypermutation and class-switch recombination of immunoglobulin genes in B cells to produce diverse immunoglobins in secretive forms. Our data indicate that glyphosate accelerates MGUS development and promotes progression to MM in genetically predisposed mice. Given that AID dysregulation is a key pathogenic driver in both MM and NHL, this work offers the first direct experimental evidence establishing glyphosate as an environmental risk factor for MM and NHL. This abstract is also being presented as Poster A50. Citation Format: Yong Li. Glyphosate as a potential carcinogen for multiple myeloma [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr PR02.