Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma

Abstract

Organochlorine exposure was linked to non-Hodgkin lymphoma (NHL) risk. To determine whether this relation is modified by immune gene variation, we genotyped 61 polymorphisms in 36 immune genes in 1172 NHL cases and 982 controls from the National Cancer Institute-Surveillance, Epidemiology, and End Results (NCI-SEER) study. We examined 3 exposures with elevated risk in this study: PCB180 (plasma, dust measurements), the toxic equivalency quotient (an integrated functional measure of several organochlorines) in plasma, and alpha-chlordane (dust measurements, self-reported termiticide use). Plasma (100 cases, 100 controls) and dust (682 cases, 513 controls) levels were treated as natural log-transformed continuous variables. Unconditional logistic regression was used to calculate beta coefficients and odds ratios, stratified by genotype. Associations between all 3 exposures and NHL risk were limited to the same genotypes for IFNG (C-1615T) TT and IL4 (5'-UTR, Ex1-168C>T) CC. Associations between PCB180 in plasma and dust and NHL risk were limited to the same genotypes for IL16 (3'-UTR, Ex22+871A>G) AA, IL8 (T-251A) TT, and IL10 (A-1082G) AG/GG. This shows that the relation between organochlorine exposure and NHL risk may be modified by particular variants in immune genes and provides one of the first examples of a potential gene-environment interaction for NHL.

Figure 1

Exposure to 5 measures of organochlorine exposure and NHL risk, stratified by genotype. Exposure and NHL risk was stratified by genotype for 2 single nucleotide polymorphisms: IFNG C−1615T (A) and IL4 5′-UTR, Ex1−168T (B). One asterisk (*) denotes significant association (P < .05) between exposure and NHL risk for that genotype. Two asterisks (**) denote highly significant association (P < .01) between exposure and NHL risk for that genotype. P value accompanies x-axis label if there was a significant interaction (P for interaction < .05) between genotype and exposure; y-axis is β coefficient from logistic regression.

Figure 2

Exposure to PCB180 levels in plasma and carpet dust and NHL risk, stratified by genotype. Exposure and NHL risk was stratified by genotype for 3 single nucleotide polymorphisms: IL16 3′-UTR, Ex22+871A>G (A), IL8 T−251A (B), and IL10 A−1082G (C). One asterisk (*) denotes significant association (P < .05) between exposure and NHL risk for that genotype. Two asterisks (**) denote highly significant association (P < .01) between exposure and NHL risk for that genotype. P value accompanies x-axis label if there was a significant interaction (P for interaction < .05) between genotype and exposure; y-axis is β coefficient from logistic regression.