Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Roundup (glyphosate) Exposure

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a lymphoid neoplasm characterized by a progressive accumulation of functionally incompetent lymphocytes, which are monoclonal in origin. CLL is used when the disease manifests primarily by lymphocytosis in blood, while the term SLL is used when involvement is predominantly in lymph nodes and/or spleen with limited peripheral blood lymphocytosis. Most commonly, there is overlap with significant lymphocytosis in blood coupled with lymphadenopathy which often increases as the disease progresses. CLL/SLL is the most common leukemia in Western countries, accounting for up to 30% of all leukemias in the United States and has a male predominance. It is more common in White Americans with median age at diagnosis of approximately 70 years and is considered a disease of older adults but is not unusual in younger individuals with the incidence increasing rapidly with increasing age.

Chronic lymphocytic leukemia (CLL) is a malignancy of CD5+ B-lymphocytes that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow, and lymphoid tissues. Surface immunoglobulin constitutes the major part of the B-cell receptor and several genetic alterations play a role in CLL pathogenesis The clinical progression of CLL is heterogeneous, with some patients requiring treatment shortly after diagnosis while others may not require therapy for many years. Multiple factors including genomic changes, patient age, and the presence of comorbidities are considered when defining the best management strategies, which include chemotherapy, chemoimmunotherapy, and/or drugs targeting B-cell receptor signaling or inhibitors of apoptosis, such as BCL-2. Research on CLL has resulted in detailed understanding of factors linked to both prognosis and approaches to treatment, selectively targeting distinctive phenotypic or physiological features of CLL.

Evidence of occupational or environmental risk factors predisposing to CLL/SLL include reports of an excess risk of CLL/SLL among farmers as well as those with benzene and heavy solvent exposure and rubber manufacturing workers. The role of environmental factors, including exposures, in CLL risk is supported by the recent finding of the significant rise in hematologic malignancy rates, including CLL and other non-Hodgkin lymphomas, representing the largest increase over last three decades due to Western lifestyle and environmental exposures.

Multiple studies have confirmed an association between occupational pesticide exposure and CLL, including the Epilymph study, a case control study of lymphoma risk from six European countries. This study found the association to be strongest for organophosphates, a class including glyphosate, with an odds ratio (OR) of 2.7. Similarly, in the MCC-Spain Study, patients in the highest tertile (3rd tertile) of exposure to insecticides, herbicides, and/or fungicides were more likely to have CLL with a 26% higher odds ratio. The highest OR was seen with herbicides at an OR of 1.9. These findings reinforce the role of environmental exposures in CLL risk.

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