Carcinogenesis Advance Access originally published online on October 20, 2006
Carcinogenesis 2007 28(3):704-712; doi:10.1093/carcin/bgl200
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Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute Rockville, MD, USA
2 The University of Sydney, Sydney Australia
3 National Centre for HIV Epidemiology and Clinical Research, Sydney Australia
4 St Vincent's Hospital, Sydney Australia
5 Viral Epidemiology Section, AVP SAIC-Frederick, NCI-Frederick, Frederick, MD, USA
6 Core Genotyping Facility, National Cancer Institute Gaithersburg, MD, USA
*To whom correspondence should be addressed at: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 8121, MSC 7240, Rockville, MD 20892-7240, USA. Tel: +1 301 451 5036; Fax: +1 301 402 1819; Email: purduem{at}mail.nih.gov
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.
Abbreviations: DLBCL, diffuse large B-cell lymphoma; FDR, false-discovery rate; FPRP, false-positive report probability; HWE, Hardy–Weinberg equilibrium; NHL, non-Hodgkin lymphoma.
Received July 7, 2006;
revised October 11, 2006;
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