title: 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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-7240, USA. coltj@mail.nih.gov
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Colt
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Richard K
authors.initials: RK
authors.lastname: Severson
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
authors.forename: Anneclaire J
authors.initials: AJ
authors.lastname: De Roos
authors.forename: Scott
authors.initials: S
authors.lastname: Davis
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007113:Immunity, Innate / Q000235:genetics*; D007378:Interleukins / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
chemical_list: D006843:Hydrocarbons, Chlorinated; D007378:Interleukins; C410127:PCB 180; D011078:Polychlorinated Biphenyls