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Genetic polymorphisms in the oxidative stress pathway and susceptibility to non-Hodgkin lymphoma

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Abstract

Oxidative damage caused by reactive oxygen species (ROS) and other free radicals is involved in a number of pathological conditions including cancer. In a population-based case-control study of non-Hodgkin lymphoma (NHL) (n = 518 cases, 597 controls) among women in Connecticut, we analyzed one or more single nucleotide polymorphisms (SNPs) in ten candidate genes (AKR1A1, AKR1C1, AKR1C3, CYBA, GPX1, MPO, NOS2A, NOS3, OGG1, and SOD2) that mediate oxidative stress directly or indirectly in the NADPH oxidase-dependent respiratory burst. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and race. Polymorphisms in AKR1A1 and CYBA were significantly associated with increased risk of NHL. There was a 1.7-fold (95% CI = 1.2–2.4, P = 0.0047) increased risk of NHL for individuals who were variant homozygous for the AKR1A1 (IVS5 + 282T > C) SNP. The effect was most pronounced for risk of diffuse large B-cell lymphoma, but risk estimates were non-significantly elevated for other common B-cell histologies and T-cell lymphomas as well. In addition, individuals variant homozygous for the CYBA (Ex4 + 11C > T) SNP had a 1.6-fold (95% CI = 1.1–2.4, P = 0.019) increased risk of NHL that was particularly pronounced for T-cell lymphoma (OR = 3.5, 95% CI = 1.3–9.6, P = 0.013), but was also associated with non-significant increased risks for each of the common B-cell histologies. These results suggest that SNPs in genes related to the oxidative stress pathway may be associated with increased risk of NHL.

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Acknowledgments

This study was supported in part by the Intramural Research Program of the NIH, National Cancer Institute and NIH grant CA62006 from the National Cancer Institute. We gratefully acknowledge the assistance of Peter Hui (Information Management Services, Inc., Silver Spring, MD, USA) for programming support.

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Correspondence to Qing Lan.

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The US Government’s right to retain a non-exclusive, royalty-free license in and to any copyright is acknowledged.

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Lan, Q., Zheng, T., Shen, M. et al. Genetic polymorphisms in the oxidative stress pathway and susceptibility to non-Hodgkin lymphoma. Hum Genet 121, 161–168 (2007). https://doi.org/10.1007/s00439-006-0288-9

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