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Carcinogenesis Advance Access first published online on October 20, 2006
This version published online on October 25, 2006
Carcinogenesis, doi:10.1093/carcin/bgl200
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received July 7, 2006
Revised October 11, 2006
Accepted October 11, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin lymphoma study

Mark P. Purdue 1 *, Qing Lan 1, Anne Kricker 2, Andrew E. Grulich 3, Claire M. Vajdic 3, Jennifer Turner 4, Denise Whitby 5, Stephen Chanock 6, Nathaniel Rothman 1, and Bruce K. Armstrong 2

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD
2 The University of Sydney, Sydney, AUS
3 National Centre for HIV Epidemiology and Clinical Research, Sydney, AUS
4 St. Vincent's Hospital, Sydney, AUS
5 Viral Epidemiology Section, AVP, SAIC-Frederick, NCI-Frederick, Frederick, MD
6 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD; Core Genotyping Facility, National Cancer Institute, Gaithersburg, MD

* To whom correspondence should be addressed.
Mark P. Purdue, E-mail: purduem{at}mail.nih.gov


  Abstract

Recent findings suggest that genetic polymorphisms in TNF and IL10 are associated with an increased risk of non-Hodgkin lymphoma (NHL), particularly for diffuse large B-cell lymphoma (DLBCL). To further investigate the contribution of common genetic variation in key cytokine and innate immunity genes to the etiology of NHL, we genotyped participants in a case-control study of NHL conducted in Australia (545 cases, 498 controls). We investigated 36 single nucleotide polymorphisms in IL10, TNF and 21 other immune function genes. We observed an elevated risk of DLBCL with the IL10 -3575T>A polymorphism (TA genotype: odds ratio (OR) 1.32, 95% confidence interval (CI) 0.86-2.02; AA, OR 1.84, 95% CI 1.10-3.08; trend test, P 0.02). Our most noteworthy TNF finding was an association between -857C>T and a decreased risk of NHL (CT or TT, OR 0.59, 95% CI 0.42-0.84, P 0.003) and particularly follicular lymphoma (OR 0.40, 95% CI 0.23-0.68, P 0.0009). Additionally, TNF -863C>A was associated with an elevated risk of DLBCL (CA, OR 1.45, 95% CI 0.95-2.21; AA, OR 2.06, 95% CI 0.88-4.83; trend test, P 0.02). Our findings offer further evidence that variation in the IL10 and TNF loci influences NHL risk. Additional studies are needed to clarify the genetic and biologic basis for these relationships.


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