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Blood, 26 February 2009, Vol. 113, No. 9, pp. 1899-1905.
Prepublished online as a Blood First Edition Paper on December 9, 2008; DOI 10.1182/blood-2008-04-153858.
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Submitted April 28, 2008
Accepted November 1, 2008
Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma
Joanne S. Colt*, Nathaniel Rothman, Richard K Severson, Patricia Hartge, James R. Cerhan, Nilanjan Chatterjee, Wendy Cozen, Lindsay M. Morton, Anneclaire J. De Roos, Scott Davis, Stephen Chanock, and Sophia S. Wang
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Karmanos Cancer Institute and Department of Family Medicine, Wayne State University, Detroit, MI, United States
Mayo Clinic, College of Medicine, Rochester, MN, United States
University of Southern California, Los Angeles, CA, United States
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, United States
Core Genotyping Facility, National Cancer Institute, Bethesda, MD, United States
* Corresponding author; email: coltj{at}mail.nih.gov.
Organochlorine exposure has been linked to non-Hodgkin lymphoma (NHL) risk. To determine whether this relationship is modified by immune gene variation, we genotyped 61 polymorphisms in 36 immune genes in 1,172 NHL cases and 982 controls from the NCI-SEER study. We examined three 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 -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 three 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 relationship 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.

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