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, Nathaniel Rothman

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1828-1834
Number of pages7
JournalCarcinogenesis
Volume27
Issue number9
DOIs
StatePublished - Sep 2006

Fingerprint

Non-Hodgkin's Lymphoma
Oxidative Stress
Odds Ratio
Confidence Intervals
Genes
B-Lymphocytes
Lymphoma, Large B-Cell, Diffuse
Homozygote
B-Cell Lymphoma
Single Nucleotide Polymorphism
Inflammation
Follicular Lymphoma
Population Control
T-Cell Lymphoma
Cell Lineage
Nitric Oxide Synthase
DNA Repair
DNA Damage
Superoxide Dismutase
Case-Control Studies

ASJC Scopus subject areas

  • Cancer Research

Cite this

Wang, S. S., Davis, S., Cerhan, J. R., Hartge, P., Severson, R. K., Cozen, W., ... Rothman, N. (2006). Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma. Carcinogenesis, 27(9), 1828-1834. https://doi.org/10.1093/carcin/bgl013

Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma. / Wang, Sophia S.; Davis, Scott; Cerhan, James R; Hartge, Patricia; Severson, Richard K.; Cozen, Wendy; Lan, Qing; Welch, Robert; Chanock, Stephen J.; Rothman, Nathaniel.

In: Carcinogenesis, Vol. 27, No. 9, 09.2006, p. 1828-1834.

Research output: Contribution to journalArticle

Wang, SS, Davis, S, Cerhan, JR, Hartge, P, Severson, RK, Cozen, W, Lan, Q, Welch, R, Chanock, SJ & Rothman, N 2006, 'Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma', Carcinogenesis, vol. 27, no. 9, pp. 1828-1834. https://doi.org/10.1093/carcin/bgl013
Wang, Sophia S. ; Davis, Scott ; Cerhan, James R ; Hartge, Patricia ; Severson, Richard K. ; Cozen, Wendy ; Lan, Qing ; Welch, Robert ; Chanock, Stephen J. ; Rothman, Nathaniel. / Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma. In: Carcinogenesis. 2006 ; Vol. 27, No. 9. pp. 1828-1834.
@article{38bfb27544dc48af89133b83f432164b,
title = "Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma",
abstract = "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.",
author = "Wang, {Sophia S.} and Scott Davis and Cerhan, {James R} and Patricia Hartge and Severson, {Richard K.} and Wendy Cozen and Qing Lan and Robert Welch and Chanock, {Stephen J.} and Nathaniel Rothman",
year = "2006",
month = "9",
doi = "10.1093/carcin/bgl013",
language = "English (US)",
volume = "27",
pages = "1828--1834",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma

AU - Wang, Sophia S.

AU - Davis, Scott

AU - Cerhan, James R

AU - Hartge, Patricia

AU - Severson, Richard K.

AU - Cozen, Wendy

AU - Lan, Qing

AU - Welch, Robert

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

PY - 2006/9

Y1 - 2006/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33747014907&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747014907&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgl013

DO - 10.1093/carcin/bgl013

M3 - Article

VL - 27

SP - 1828

EP - 1834

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 9

ER -