Genetic polymorphisms in glutathione S-transferase mu and theta, N-acetyltransferase, and CYP1A1 and risk of gliomas.
The role of genetic polymorphisms in modulating susceptibility to carcinogenic exposures has been well explored for tobacco-related neoplasms but not for other neoplasms including gliomas. It is relevant to explore these polymorphisms because certain carcinogenic exposures such as nitrosamines are implicated in the risk of gliomas. We therefore conducted a pilot case-control study to examine the role of polymorphisms in GSTM1, GSTT1, NAT2 (rapid, intermediate, and slow acetylation), and CYP1A1 and risk of glioma. Ninety patients diagnosed with glioma were ascertained as part of an ongoing genetic epidemiological study and were age, gender, and race matched with 90 healthy controls. We used PCR based methodology to determine the prevalence of the above genetic polymorphisms using sequences and PCR conditions directly adapted from studies reported previously. We calculated univariate odds ratios and performed multiple logistic regression to assess interactions between polymorphisms. We found no statistically significant associations between the null genotypes of GSTM1 and GSTT1, and CYP1A1 and risk of gliomas. However, there was an intriguing pattern with NAT2 acetylation status (odds ratios, 1.81, 1.34, and 0.61 for rapid, intermediate, and slow acetylation, respectively; P = 0.10 for trend). It is unlikely that any single polymorphism is sufficiently predictive of risk, and a panel of markers integrated with epidemiological data should be conducted on a large number of study subjects to fully understand the role of genetic polymorphisms and brain tumor risk.
Trizna
Z
Z
Department of Dermatology, The University of Texas Medical Branch at Galveston, 77555-0783, USA.
de Andrade
M
M
Kyritsis
A P
AP
Briggs
K
K
Levin
V A
VA
Bruner
J M
JM
Wei
Q
Q
Bondy
M L
ML
D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005910:Glioma / Q000201:enzymology* / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D012306:Risk; D012307:Risk Factors; D013781:Texas
D017931:DNA Primers; D019363:Cytochrome P-450 CYP1A1; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase