Exposure to Pesticides as Risk Factor for Non-Hodgkin's Lymphoma and Hairy Cell Leukemia: Pooled Analysis of Two Swedish Case-control Studies

Abstract

Increased risk for non-Hodgkin's lymphoma (NHL) following exposure to certain pesticides has previously been reported. To further elucidate the importance of phenoxyacetic acids and other pesticides in the etiology of NHL a pooled analysis was performed on two case-control studies, one on NHL and another on hairy cell leukemia (HCL), a rare subtype of NHL. The studies were population based with cases identified from cancer registry and controls from population registry. Data assessment was ascertained by questionnaires supplemented over the telephone by specially trained interviewers. The pooled analysis of NHL and HCL was based on 515 cases and 1141 controls. Increased risks in univariate analysis were found for subjects exposed to herbicides (OR 1.75, CI 95% 1.26-2.42), insecticides (OR 1.43, CI 95% 1.08-1.87), fungicides (OR 3.11, CI 95% 1.56-6.27) and impregnating agents (OR 1.48, CI 95% 1.11-1.96). Among herbicides, significant associations were found for glyphosate (OR 3.04, CI 95% 1.08-8.52) and 4-chloro-2-methyl phenoxyacetic acid (MCPA) (OR 2.62, CI 95% 1.40-4.88). For several categories of pesticides the highest risk was found for exposure during the latest decades before diagnosis. However, in multivariate analyses the only significantly increased risk was for a heterogeneous category of other herbicides than above.

Re-registration Challenges of Glyphosate in the European Union

“…Critical gaps in the re-registration of glyphosate, including the EU re-registration process itself, have been addressed (European Parliament Council, 2002;Myers et al, 2016), particularly those considered more pressing by recent scientific findings. These include: (a) increasing exposures of EU citizens to glyphosate residues, supported by human and environmental biomonitoring data in limited number (Curwin et al, 2007;Mesnage et al, 2012;Krüger et al, 2014;Niemann et al, 2015;Connolly et al, 2017;Conrad et al, 2017;Mills et al, 2017;Vandenberg et al, 2017), but identifying a clearly rising trend; (b) carcinogenicity classification by IARC, evidence of linkages of glyphosate or its formulated products to non-Hodgkin's lymphoma (Hardell et al, 2002;De Roos et al, 2003Eriksson et al, 2008;Schinasi and Leon, 2014;Mesnage et al, 2015b), and effective dose levels indicated in rodent oncogenicity studies being 1-2 orders of magnitude lower when formulated glyphosate-based herbicides were used compared to those obtained with the pure active ingredient; (c) evidence of contributions to fatal chronic kidney disease by glyphosate in areas with heavy metals in water (Jayasumana et al, 2014(Jayasumana et al, , 2015 and the finding of nonalcoholic fatty liver disease upon exposure to a glyphosatebased herbicide (Roundup R ) (Mesnage et al, 2017b), coupled with the powerful animal metabolism data embedded within the re-registration document appendices (showing glyphosate and AMPA levels higher in kidney than in liver, and much higher than in muscle tissue); as well as (d) problems (e.g., risk assessment studies for regulatory purposes of re-registration of glyphosate being carried out with pure glyphosate) arising from the dual character of pesticide registration in the EU with active ingredients authorized at EU and formulated products at MS level (Klátyik et al, 2017a). In light of these findings, earlier risk assessment statements (Williams et al, 2000) are untenable for both hazard and exposure levels.…”

“…Among environmental factors, glyphosate or its formulated products have been indicated to be linked with increased incidence of and mortality by multiple diseases (including cataract related to subsequent breast carcinoma) and cancer (Swanson et al, 2014;Singh et al, 2017). In the latter category, associations were found with non-Hodgkin lymphoma or multiple myeloma incidence (Hardell and Eriksson, 1999;McDuffie et al, 2001;Hardell et al, 2002;De Roos et al, 2003Eriksson et al, 2008;Schinasi and Leon, 2014;Mesnage et al, 2015b), although other reviews claimed no causal relationship between exposure to glyphosate and lymphohematopoietic cancers (Acquavella et al, 2016;Chang and Delzell, 2016;Williams et al, 2016a). Some of these findings have been questioned by Monsanto (Acquavella et al, 1999) and a recent cohort prospective epidemiology study carried out in the US on 57310 licensed pesticide applicators and 32347 spouses in Iowa or North Carolina States found no apparent correlation between glyphosate use and solid tumor or lymphoid malignancies, including non-Hodgkin lymphoma, except for increased risk of acute myeloid leukemia in case of high exposure (Andreotti et al, 2018).…”

Pesticide exposure as risk factor for non‐Hodgkin lymphoma including histopathological subgroup analysis

“…Furthermore, a meta-analysis combining that study with an investigation on hairy-cell leukaemia, a rare NHL variant, showed an OR for glyphosate of 3.04 (95% CI 1.08-8.52). 36 Recent findings from other groups also associate glyphosate with different B-cell malignancies such as lymphomas and myeloma. 32,37,38 Glyphosate has succeeded MCPA as one of the most used herbicides in agriculture, and many individuals that used MCPA earlier are now also exposed to glyphosate.…”

Non‐Hodgkin's lymphoma among asthmatics exposed to pesticides

“…9,10 Exposure to pesticides has also been suggested as a possible risk factor for NHL. [11][12][13][14][15] Pesticides may increase cancer risk by altering the immune system. 16 -19 Because both asthma and pesticide exposure may change the risk of NHL by immunologic alterations, we investigated the relation between pesticide exposure, asthma and risk of NHL.…”