Agricultural risk factors for t(14;18) subtypes of non-Hodgkin’s lymphoma

Abstract

The t(14;18) translocation is a common somatic mutation in non-Hodgkin's lymphoma (NHL) that is associated with bcl-2 activation and inhibition of apoptosis. We hypothesized that some risk factors might act specifically along t(14;18)-dependent pathways, leading to stronger associations with t(14;18)-positive than t(14;18)-negative non-Hodgkin's lymphoma. Archival biopsies from 182 non-Hodgkin's lymphoma cases included in a case-control study of men in Iowa and Minnesota (the Factors Affecting Rural Men, or FARM study) were assayed for t(14;18) using polymerase chain reaction amplification; 68 (37%) were t(14;18)-positive. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for various agricultural risk factors and t(14;18)-positive and -negative cases of non-Hodgkin's lymphoma, based on polytomous logistic regression models fit using the expectation-maximization (EM) algorithm. T(14;18)-positive non-Hodgkin's lymphoma was associated with farming (OR 1.4, 95% CI = 0.9-2.3), dieldrin (OR 3.7, 95% CI = 1.9-7.0), toxaphene (OR 3.0, 95% CI = 1.5-6.1), lindane (OR 2.3, 95% CI = 1.3-3.9), atrazine (OR 1.7, 95% CI = 1.0-2.8), and fungicides (OR 1.8, 95% CI = 0.9-3.6), in marked contrast to null or negative associations for the same self-reported exposures and t(14;18)-negative non-Hodgkin's lymphoma. Causal relations between agricultural exposures and t(14;18)-positive non-Hodgkin's lymphoma are plausible, but associations should be confirmed in a larger study. Results suggest that non-Hodgkin's lymphoma classification based on the t(14;18) translocation is of value in etiologic research.

BCL‐2/JH translocation in peripheral blood lymphocytes of unexposed individuals: Lack of seasonal variations in frequency and molecular features

“…The recent evidence that t(14;18)-positive NHL might be associated with farming, 29 reinforces the hypothesis that BCL-2/J H translocation could be a relevant biomarker to evaluate the risk associated with pesticide use.…”

The non-Hodgkin lymphomas: A review of the epidemiologic literature

“…148,149 Compared to t(14;18)-negative NHL cases, cases who were t(14;18)-positive were more likely to report exposure to insecticides, organophosphates, carbamates, traizines and fungicides. 59 None of these findings was statistically significant, however. Associations for phenoxy acid herbicides were approximately 1.0 for both t(14;18)-positive and -negative cases compared with controls.…”

“…Significantly elevated odds of NHL were reported in association with exposure to lindane, dieldrin and toxaphene among persons with the t(14;18) chromosomal translocation, a common somatic mutation hypothesized to be an early step in the pathogenesis. 153 These associations have not been confirmed in larger studies, however.…”

“…Schroeder et al 59 used archival samples collected from white male participants in the National Cancer Institute's Factors Affecting Rural Men (FARM) study to evaluate the associations between t(14;18)-positive and t(14;18)-negative NHL and agricultural factors. The t(14;18) translocation is a common somatic mutation in NHL and may be a necessary component in the causal pathway of certain NHL types, especially follicular lymphoma and some diffuse large B-cell lymphomas.…”

“…Associations for phenoxy acid herbicides were approximately 1.0 for both t(14;18)-positive and -negative cases compared with controls. 59 Hartge et al 102 examined the effects of residential herbicide exposure and risk of NHL, and reported no association with weed treatment (RR 5 1.02, 95% CI: 0.84-1.23). Furthermore, there was no significant trend in association with years of treatment, number of treatments, or total applications (p for trend > 0.38 for all categories of exposure).…”