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

Lan, Qing; Zheng, Tongzhang; Shen, Min; Zhang, Yawei; Wang, Sophia; Zahm, Shelia Hoar; Holford, Theodore R.; Leaderer, Brian P.; Boyle, Peter; Chanock, Stephen J.

doi:10.1007/s00439-006-0288-9

Cited by 58 publications

(45 citation statements)

References 42 publications

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“…Statistically significant differences in DLBCL and FL were shown for T/T homozygotes only. By contrast, Lan et al (13) found no difference between patients and healthy blood donors regarding this polymorphism in a study of 161 DLBCL and 119 FL patients. Smedby et al (11) suggested that polymorphic variation in the XRCC3 gene, but not in the ERCC2 and XRCC1 genes, may be essential in the pathogenesis of FL.…”

Section: Discussionmentioning

confidence: 87%

“…Specifically, Wang et al (12) observed that the rs2297518 Leu/Leu variation in nitric oxide synthase (NOS) NOS2A results in a 3.4-fold increased risk of diffuse large B-cell lymphoma (DLBCL) and a 2.6-fold increased risk of FL. By contrast, Lan et al (13), who evaluated SNPs in oxidative stress genes including NOS2A in another population, did not detect any statistically significant associations between analyzed SNPs and risk of NHL, with the exception of SNPs in AKR1A1 and CYBA (13). Recently, a pooled analysis of SNPs in 27 gene regions involved in DNA repair based on three studies of almost 2,000 cases and 1,800 controls was published by Shen et al (14).…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms of DNA repair and oxidative stress genes in B-cell lymphoma patients

Fabisiewicz¹,

Pacholewicz²,

Paszkiewicz‐Kozik

et al. 2012

Biomedical Reports

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Abstract. The purpose of the study was to investigate the possible association between ERCC2 rs28365048, ERCC5 rs17655, XRCC3 rs861539 and NOS2A rs2297518 polymorphisms with B-cell lymphoma. The study was conducted on 189 patients with CD20 + B-cell lymphoma and 193 controls. The genotype frequencies were compared in the patient and control groups using quantitative polymerase chain reaction, based on allelic discrimination analysis. Our results indicated that variation in NOS2A may be significant in B-cell lymphoma in a population ≥50 years old (OR=2.15; 95% CI, 1.17-3.92; P=0.013). No association was observed between variations in ERCC2, ERCC5, XRCC3 and B-cell lymphoma in the studied population. Our finding of an association between age and NOS2A polymorphisms in lymphoma is unique and requires additional studies. The results concerning ERCC2, ERCC5 and XRCC3 variations add additional data to studies on genetic polymorphisms in the DNA repair pathway.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Polymorphisms of DNA repair and oxidative stress genes in B-cell lymphoma patients

Fabisiewicz¹,

Pacholewicz²,

Paszkiewicz‐Kozik

et al. 2012

Biomedical Reports

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“…An increased lymphoma risk was attributed to the frequent genetic polymorphism 242C>T in the CYBA subunit of NAD(P)H oxidase in one study (26), but not in another (27). Moreover, 242C>T in CYBA and another genetic polymorphism in NCF4 were associated with chronic doxorubicin-induced cardiomyopathy (28).…”

Section: Introductionmentioning

confidence: 92%

A Functional Polymorphism in the NAD(P)H Oxidase Subunit CYBA Is Related to Gene Expression, Enzyme Activity, and Outcome in Non–Hodgkin Lymphoma

Hoffmann

Schirmer²,

Tzvetkov³

et al. 2010

Cancer Research

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NAD(P)H oxidase is a major endogenous source of reactive oxygen species (ROS). ROS may not only be involved in carcinogenesis but also in efficacy of chemotherapeutic agents like doxorubicin. By a comprehensive genotyping approach covering 48 genetic polymorphisms (single-nucleotide polymorphisms) in five subunits of phagocytic NAD(P)H oxidase, we asked whether they affect gene expression, enzymatic activity, and outcome of CHO(E)P chemotherapy. A highly consistent effect was observed for the CYBA 640A>G variant. In peripheral blood granulocytes of 125 healthy volunteers, the G allele of 640A>G was associated with lower NAD(P)H oxidase activity (P = 0.006). Moreover, the G allele was associated with lower mRNA and protein expression (both P = 0.02). Of clinical importance, the outcome of patients suffering from non-Hodgkin lymphoma and treated with CHO(E)P regimen was dependent on the CYBA 640A>G polymorphism. In an exploratory study (n = 401), carriers of 640GG had an event-free survival (EFS) risk ratio of 1.95 [95% confidence interval (95% CI), 1.31-2.90; P = 0.001] compared with 640AA. In a confirmatory set (n = 477), the risk ratios were 1.53 (1.04-2.25, P = 0.03). The complete set of 878 patients showed a relative risk of 1.72 (1.30-2.26) and 1.59 (1.14-2.21) for EFS and overall survival, respectively. Further molecular-biological experiments showed lower expression and reduced stability of transcripts with the G allele in lymphoblastoid cell lines. Transfection of allele-specific plasmids into HEK293 cells elicited lower activity for the G allele in a luciferase reporter gene construct. Thus, CYBA 640A>G was shown to be a functional polymorphism with possible consequences for patients receiving CHO(E)P chemotherapy and might have further implications for other ROS-mediated modalities. Cancer Res; 70(6); 2328-38. ©2010 AACR.

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“…The few studies on the rs7195830 polymorphism have not elucidated the mechanisms underlying this result, but this polymorphism was also selected as an oxidative stress-related locus in several previous studies on non-Hodgkin lymphoma and cervical cancer. 13,14 It is possible that the rs7195830 polymorphism, which is located in the 3¢-untranslated region, might influence messenger RNA stability or modulate the transcription rate and affect reactive oxygen species generation. Further investigations on the function of this polymorphism are necessary.…”

Section: Discussionmentioning

confidence: 99%

“…Rather, rs7195830 has been mentioned in studies on non-Hodgkin lymphoma and cervical cancer as an oxidative stress-related locus. 13,14 Therefore, in the present study, we hypothesized that the rs1049255 and rs7195830 polymorphisms of the CYBA gene are associated with arterial elasticity indices in a large cohort of apparently healthy Chinese individuals across a wide age range. As physical activity may influence oxidative stress biomarkers, 15 we further explored whether physical activity could modify the genetic effect.…”

Section: Introductionmentioning

confidence: 99%

Physical activity modifies the association between CYBA gene polymorphisms and small artery elasticity in a Chinese population

et al. 2012

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Emerging evidence suggests that increased superoxide production is responsible for a significant proportion of endothelial dysfunction. The relationship between variants of the CYBA gene and cardiovascular diseases is currently debated. In the present study, we investigated the influence of CYBA polymorphisms (rs1049255 and rs7195830) on arterial elasticity in a Chinese population. In the 2178 participants enrolled in the GaoYou study, we measured large artery elasticity (C1) and small artery elasticity (C2) non-invasively, genotyped the CYBA polymorphisms and calculated energy expenditure. The AA genotype of the rs1049255 polymorphism was associated with a lower C2 than were the GG/AG genotypes (5.31 ± 0.11 vs. 5.52 ± 0.06 ml mm Hg À1 Â100; P¼0.01). Further analyses revealed an interaction between CYBA polymorphisms and physical activity with respect to C2 (P¼0.007 for rs1049255 and P¼0.038 for rs7195830). In less physically active participants, the AA genotype of the rs1049255 polymorphism was associated with a significantly lower C2 than the GG/AG genotypes (4.69 ± 0.16 vs. 5.26 ± 0.19 ml mm Hg À1 Â100; P¼0.008). In physically active participants, the GG/AG genotypes of rs7195830 polymorphism were correlated with higher C2 values than the AA genotype (5.84±0.08 vs. 5.08±0.32 ml mm Hg À1 Â100; P¼0.049). Haplotype analyses revealed higher C2 values in rs1049255G-rs7195830G carriers (P¼0.0015). In conclusion, the rs1049255 and rs7195830 polymorphisms of the CYBA gene were associated with C2 in a Chinese population; physical activity could modify this genetic effect.

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

Cited by 58 publications

References 42 publications

Polymorphisms of DNA repair and oxidative stress genes in B-cell lymphoma patients

Polymorphisms of DNA repair and oxidative stress genes in B-cell lymphoma patients

A Functional Polymorphism in the NAD(P)H Oxidase Subunit CYBA Is Related to Gene Expression, Enzyme Activity, and Outcome in Non–Hodgkin Lymphoma

Physical activity modifies the association between CYBA gene polymorphisms and small artery elasticity in a Chinese population

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