Journal Article

Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma

Sophia S. Wang, Scott Davis, James R. Cerhan, Patricia Hartge, Richard K. Severson, Wendy Cozen, Qing Lan, Robert Welch, Stephen J. Chanock and Nathaniel Rothman

in Carcinogenesis

Volume 27, issue 9, pages 1828-1834
ISSN: 0143-3334
Published online March 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl013
Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Evidence supporting the contribution of oxidative stress to key pathways in cancer, such as inflammation and DNA damage, continues to mount. We investigated variations within genes mediating oxidative stress to determine whether they alter risk for non-Hodgkin lymphoma (NHL). Thirteen single nucleotide polymorphisms (SNPs) from 10 oxidative stress genes (AKR1A1, AKR1C1, CYBA, GPX, MPO, NOS2A, NOS3, OGG1, PPARG and SOD2) were genotyped in 1172 NHL cases and 982 population-based controls from a USA multicenter case–control study. For NHL and five subtypes (diffuse large B-cell, follicular, marginal zone, small lymphocytic and T-cell), SNP associations were calculated. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for sex, age (<45, 45–64, 65+ years), race (white, black, other) and study site. Overall, the oxidative stress pathway was associated significantly with the B-cell NHL subtype, diffuse large B-cell lymphoma (DLBCL) (global P-value = 0.003). Specifically, for nitric oxide synthase (NOS2A Ser608Leu, rs2297518) Leu/Leu homozygotes, there was a 2-fold risk increase for NHL (OR = 2.2, 95% CI = 1.1–4.4) (referent = Ser/Ser and Ser/Leu). This risk increase was consistent by cell lineage (B- and T-cell NHL) and pronounced for the two most common subtypes, diffuse large B-cell (OR = 3.4, 95% CI = 1.5–7.8) and follicular lymphoma (OR = 2.6, 95% CI = 1.0–6.8). In an analysis of manganese superoxide dismutase (SOD2 Val16Ala, rs1799725) Ala/Ala homozygotes, we observed moderately increased risks for B-cell lymphomas (OR = 1.3, 95% CI = 1.0–1.6; referent = Val/Val and Val/Ala) that was consistent across the B-cell subtypes. Genetic variations that result in an increased generation of reactive oxygen species appear to increase risk for NHL and its major subtypes, particularly DLBCL. Independent replication of our findings are warranted and further evaluation of oxidative stress in the context of inflammation, DNA repair and the induction of the NF-κB pathway may further reveal important clues for lymphomagenesis.

Journal Article.  5474 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.