8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker of oxidative damage in oesophageal cancer patients: lack of association with antioxidant vitamins and polymorphism of hOGG1 and GST.
BACKGROUND
The present report was designed to investigate the origins of elevated oxidative stress measured in cancer patients in our previous work related to a case-control study (17 cases, 43 controls) on oesophageal cancers. The aim was to characterize the relationship between the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), antioxidant vitamins and genetic susceptibility.


METHODS
8-oxodG was analysed in peripheral blood mononuclear cells (PBMCs) by High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED). Analysis of gene polymorphisms in GSTM1 and GSTT1 was performed by multiplex PCR and in GSTP1 and hOGG1 by a PCR-RFLP method. Reversed-phase HPLC with UV detection at 294 nm was used to measure vitamins A and E in serum from the same blood samples.


RESULTS
We observed that in our combined population (cases and control, n = 60), there was no statistically significant correlation between the levels of 8-oxodG and (i) the serum concentration of antioxidant vitamins, vitamin A (P = 0.290) or vitamin E (P = 0.813), or (ii) the incidence of the Ser326Cys polymorphic variant (P = 0.637) of the hOGG1 gene. Also, the levels of 8-oxodG were not significantly associated with polymorphisms in metabolite-detoxifying genes, such as GSTs, except for the positive correlation with Val/Val GST P1 allele (P < 0.0001).


CONCLUSIONS
The weakness of our cohort size notwithstanding, vitamins levels in serum and genetic polymorphisms in the hOGG1 or GST genes do not appear to be important modulators of 8-oxodG levels.
Groupe Régional d'Etudes sur le Cancer-UPRES EA 1772-IFR 146, Université de Caen-Basse-Normandie and Centre de Lutte Contre le Cancer François Baclesse, Caen, France.
Stéphanie
S
Lagadu
Mathilde
M
Lechevrel
François
F
Sichel
Jean
J
Breton
Didier
D
Pottier
Rémy
R
Couderc
Fathi
F
Moussa
Virginie
V
Prevost
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D045647:DNA Glycosylases / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000097:blood; D004938:Esophageal Neoplasms / Q000097:blood* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005981:Glutathione Synthase / Q000235:genetics; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D014815:Vitamins / Q000097:blood
D000975:Antioxidants; D014408:Biomarkers, Tumor; D014815:Vitamins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D005981:Glutathione Synthase; D003849:Deoxyguanosine