Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin's lymphoma.
OBJECTIVE
The risk of non-Hodgkin's lymphoma (NHL) has been associated with inflammation. One possible mechanism may involve oxidative stress as reactive oxygen species (ROS) can generate pro-inflammatory signals. Anti-oxidant enzymes including superoxide dismutase, glutathione peroxidase and catalase protect against the harmful effects of ROS. Genetic variation in the genes coding for these enzymes (SOD2, GPX1, and CAT, respectively) alters ROS production and therefore may provide a mechanism for the relationship between inflammation and NHL.


METHODS
Data from two population-based, case-control studies of lymphoma in the UK (700 cases and 915 controls) and USA (1593 cases and 2517 controls) were pooled to analyze polymorphisms in genes involved in the oxidative stress response (SOD2 Val16Ala, CAT C-262T and GPX1 Pro197Leu).


RESULTS
No associations were observed between SOD2 Val16Ala and CAT C-262T and total NHL, diffuse large-B cell lymphoma or follicular lymphoma. However, when we looked at marginal zone lymphoma, a specific subtype of lymphoma characterised by inflammation, we found that homozygosity for the SOD2 16Ala allele was associated with a decreased risk among UK study participants. The GPX1 197Leu allele was weakly associated with NHL and follicular lymphoma.


CONCLUSIONS
Analysis of genetic variation in oxidative stress genes in two lymphoma case-control studies suggests a possible role for oxidative stress in the risk of NHL. The risk modification is seen predominantly for marginal zone lymphomas which frequently arise in the context of chronic inflammation. However, in order to clarify the role of oxidative stress in the etiology of NHL analyses of additional polymorphisms and haplotypes in these and other genes involved in the oxidative stress response are needed.
Lightfoot
Tracy J
TJ
Epidemiology & Genetics Unit, University of York, York, YO10 5DD, UK. tracy.lightfoot@egu.york.ac.uk
Skibola
Christine F
CF
Smith
Alex G
AG
Forrest
Matthew S
MS
Adamson
Peter J
PJ
Morgan
Gareth J
GJ
Bracci
Paige M
PM
Roman
Eve
E
Smith
Martyn T
MT
Holly
Elizabeth A
EA
D000328:Adult; D000368:Aged; D002374:Catalase / Q000235:genetics; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D013482:Superoxide Dismutase / Q000235:genetics
D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase