Genetic polymorphisms in the oxidative stress pathway and susceptibility to non-Hodgkin lymphoma |
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Authors: | Qing Lan Tongzhang Zheng Min Shen Yawei Zhang Sophia S Wang Shelia H Zahm Theodore R Holford Brian Leaderer Peter Boyle Stephen Chanock |
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Institution: | (1) Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, MSC 7240, 6120 Executive Blvd., EPS 8109, Bethesda, MD 20892-7240, USA;(2) Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, CT, USA;(3) International Agency for Research on Cancer, Lyon, France;(4) Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, DHHS, Bethesda, MD, USA |
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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.
Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.
The US Government’s right to retain a non-exclusive, royalty-free license in and to any copyright is acknowledged. |
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Keywords: | Non-Hodgkin lymphoma Oxidative stress Genetic polymorphism |
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