Exposure to Glyphosate Linked to Non-Hodgkin Lymphoma and Multiple Myeloma

In this study, Chinese scientists working at Lerner Research Institute at the Cleveland Clinic in Cleveland, Ohio, found that mice exposed to glyphosate exhibit multiple blood and plasma abnormalities and damage to bodily organs. They also discovered that exposure to glyphosate induced in the mice a biochemical mechanism that is known to play a role in the development of two types of blood cancers: multiple myeloma (MM) and B-cell lymphoma, which accounts for approximately 90% of non-Hodgkin lymphoma (NHL).

It is one thing to find a significant association between a toxic chemical and a disease, such as the link found in this study between glyphosate exposure and kidney and liver damage. It takes additional evidence to move from there to a conclusion that there is a causative relationship at work—to say the toxin is causing the disease.

To establish causation, scientists study the effects of the toxin in animals that have biological similarities to humans. They look for changes at the cellular and molecular level that might reveal the biological pathways that lead from toxin exposure to the appearance of the disease.

“We uncover a B cell-specific mutational mechanism for glyphosate exposure that increases MM and NHL risk, providing a molecular basis for human epidemiological findings.” – Lei Wang et al. See study details below.

Glyphosate Exposure Induces Key Mechanism in Cancer Pathway

Unlike prior mouse glyphosate carcinogenicity studies, the Wang authors used a mouse strain that is “widely regarded as the best animal model for MM.”

Their study found that exposure to glyphosate activates a key mechanism known to play a role in the development of non-Hodgkin lymphoma and multiple myeloma. Activation-induced cytidine deaminase (also known as AID) is an enzyme that creates mutations in DNA. It does this by actually altering the base pairs that form the “stair steps” in the DNA double-helix ladder. A guanine-cytosine pairing might be converted to an adenine-thymine pair. AID can result in multiple DNA mutations, some occurring when DNA repair mechanisms are engaged.

AID can produce beneficial results for the immune system, but it can also lead to B-cell lymphoma. Wang et al found that glyphosate exposure caused an increase in the production of AID in the spleen and bone marrow in the study mice. AID, they write, “is a B cell-specific genome mutator and a key pathogenic player in both MM and B cell lymphoma.”

“Our data disclose, for the first time, that glyphosate elicits a B cell-specific mutational mechanism of action in promoting carcinogenesis, as well as offering experimental evidence to support the epidemiologic finding regarding its tissue specificity in carcinogenesis (i.e., only increasing the risk for MM and NHL)." – Lei Wang et al. See study details below.

The authors of this study make a very important observation related to causality. While previous studies have revealed several mechanisms by which glyphosate can induce DNA damage, they “failed to explain why glyphosate is only positively associated with MM and NHL.” The discovery of a mechanism that is specifically tied to the two cancers most associated with glyphosate offers strong evidence that glyphosate is causing these diseases.

It should be noted that both of the plaintiffs in the most recent Roundup trial, Alva and Alberta Pilliod, got B-cell lymphoma after using Roundup.

Blood Abnormalities and Organ Damage

The researchers also found that exposure to glyphosate damaged several organs and produced blood abnormalities in the mice that mirror conditions that precede or coincide with multiple myeloma and NHL.

• Exposure to glyphosate triggered “multiple organ dysfunction” in the mice, including:
  • Bone lesions
  • Liver damage
  • Severe lung damage
  • Kidney damage

• Mice exposed to glyphosate in their drinking water developed “progressive plasma cell neoplasms.” (A neoplasm is an abnormal tissue growth characteristic of cancer. Plasma cells are derived from white blood cells called B cells and help the body fight foreign substances.) The exposed mice exhibited “a marked increase” in plasma cells in the spleen and bone marrow. An increase in plasma cells is characteristic of a condition that nearly always precedes multiple myeloma known as monoclonal gammopathy of undetermined significance, or MGUS. MGUS itself usually harmless, but can progress to more serious disease, including blood cancers.

• Exposure to glyphosate also produced increased levels of immunoglobin G (IgG), the most common type of antibody found in the blood and body fluids. According to the authors, the steadily increasing IgG levels suggest that exposure to glyphosate induces in mice a condition that is “equivalent to human MGUS.” Increases in IgG are also frequently found in patients with Hodgkin and non-Hodgkin lymphoma.

The full study is available online.

Summary Information

Title
Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice

Authors
Lei Wang^1,2, Qipan Deng¹, Hui Hu^1,3, Ming Liu^1,4, Zhaojian Gong^1,5, Shanshan Zhang^1,6, Zijun Y. Xu-Monette⁷, Zhongxin Lu³, Ken H. Young⁷, Xiaodong Ma^1,8,9, and Yong Li¹

1. Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
2. School of Life Sciences, Institute of Modern Aquaculture Science and Engineering, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, South China Normal University, Guangzhou 510631, China.
3. Department of Medical Laboratory, Central Hospital of Wuhan, Wuhan, China.
4. State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
5. Department of Stomatology, the Second Xiangya Hospital, Central South University, Changsha, China.
6. Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China.
7. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
8. Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China.
9. The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

Journal
Journal of Hematology & Oncology (2019),12(1):70

Funding
YL is supported in part by NIH R01 grants (CA138688 and CA177810); LW is supported by National Natural Science Foundation of China (NO. 31500326) and Natural Science Foundation of Guangdong Province of China (NO. 2017A030313194).