This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Peters, E. S. Articles by Wrensch, M. R. Search for Related Content PubMed PubMed Citation Articles by Peters, E. S. Articles by Wrensch, M. R.

NAT2 and NQO1 Polymorphisms Are Not Associated with Adult Glioma¹

Departments of Cancer Cell Biology [E. S. P., K. T. K., S. P.], Oral Epidemiology [E. S. P.], and Oral Medicine [E. S. P.], Harvard University, Boston, Massachusetts 02115, and Department of Epidemiology and Biostatistics, University of California, San Francisco, California 94143 [J. K. W., P. C., R. M., M. R. W.]

	Introduction

Top Introduction Materials and Methods Results References

 
Although various carcinogenic agents (e.g., ionizing radiation, polycyclic aromatic hydrocarbons, N-nitroso compounds, dietary nitrosamines, organic solvents, unfiltered cigarettes, and pesticides) have been suggested as possible risk factors for brain cancer, none have emerged as dominant factors. The etiology of most of brain tumors continues to be poorly understood (1) . A genetically based difference in susceptibility to carcinogens may play a role in the development of glioma.

Few studies have examined the relationship between genetic polymorphisms of metabolizing enzymes and glioma risk. The finding by Trizna et al. (2) of a suggestive, but nonsignificant, elevation in glioma risk for the rapid NAT2 acetylator genotype suggested that further exploration of this polymorphism might be worthwhile. If aromatic/heterocyclic amines are associated with gliomas, then functional variations in enzymes that metabolize these carcinogens might modify the risk for glioma among exposed individuals. To evaluate this possibility, we examined NAT2 and NQO1 polymorphisms in conjunction with smoking history in adult glioma cases and controls.

	Materials and Methods

Top Introduction Materials and Methods Results References

 
The 159 cases and 163 controls in this study have been described elsewhere (3 , 4) . DNA samples, obtained from whole blood, were genotyped for NAT2 with a modification of the PCR-RFLP method of Bell et al. (5) that allows classification of individuals as slow versus rapid acetylators. NQO1 has been demonstrated to be polymorphic (C-to-T transition at bp 609), and a 3-fold decrease in reductase activity is associated with this allelic variant. Genotyping for NQO1 used the PCR method described previously by Wiencke et al. (6) . Unadjusted ORs³ and 95% CIs comparing NAT2 and NQO1 genotypes and smoking histories of white cases and controls were estimated with unconditional logistic regression analyses. Analyses of smoking history were stratified by genotypes. Analyses also were adjusted for subjects’ age and gender.

	Results

Top Introduction Materials and Methods Results References

 
For NAT2, 63% of cases and 54% of controls had the slow acetylator genotype, but this difference was not significantly different (P > 0.05). Overall, in both unadjusted and adjusted comparisons, cases were somewhat (40–50%, respectively) more likely than controls to have the NAT2 slow acetylator genotype (Table 1) . Among subjects with fast acetylator genotypes, cases appeared to be more likely than controls to have smoked unfiltered cigarettes, but these results were not significant, and the CI was very wide (case-control OR for having smoked unfiltered cigarettes versus never smoked, 3.6; 95% CI, 0.4–36.9). The ORs for smoking filtered cigarettes versus never smoking and the ORs for smoking either filtered or unfiltered cigarettes among those subjects with NAT2 slow acetylator genotypes were all very close to 1. Looked at another way, among subjects who never smoked or who smoked filtered cigarettes, cases were somewhat more likely than controls to have slow acetylator genotypes, whereas among subjects who smoked unfiltered cigarettes, cases were less likely than controls to have slow acetylator genotypes. Almost identical percentages of cases (32%) and controls (34%) were heterozygous for the NQO1 variant, whereas 4% of both cases and controls were homozygous for this variant. Importantly, all of these findings were compatible with chance.

Study Limitations.
Although adequate power was available to detect an association between genotype and glioma, power may have been insufficient to detect an interaction between NAT2 and smoking with glioma. In addition, exposure misclassification, selection, and recall bias are concerns in case-control studies and may have influenced the observed results.

In conclusion, these results provide no support for an association of NQO1 variant genotype and glioma. The results also do not support the hypothesis suggested by Trizna et al. (2) that the NAT2 fast acetylator genotype might increase the risk of gliomas. Trizna et al. (2) reported a 1.6-fold (0.84–3.17) elevation in risk for the NAT2 fast acetylator genotype from a case-control study of 90 cases and 90 controls. In our somewhat larger study, we observed the opposite, a 1.4-fold OR of glioma with the NAT2 slow acetylator genotype. Although some of the discrepancy between the two studies may be attributable to variations in genotype frequencies in the control populations, that variation is unlikely to be solely responsible for the magnitude of difference between the two studies.

	Acknowledgments

 
We thank Dr. Nancy Mueller for helpful comments on the manuscript.

	Footnotes

 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institute of Environmental Health Sciences Grants P42ES04705, ES00002, and ES06717, National Cancer Institute Grants CA57220 and CA52689, National Institute of Dental Research Grant DE-92-05, and a grant from The Brain Tumor Society.

² To whom requests for reprints should be addressed, at Oral Medicine and Dentistry, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115.

³ The abbreviations used are: OR, odds ratio; CI, confidence interval.

Received 3/22/00; revised 10/24/00; accepted 11/27/00.

	References

Top Introduction Materials and Methods Results References

 

1. Wrensch M., Bondy M. L., Wiencke J., Yost M. Environmental risk factors for primary malignant brain tumors: a review.. J. Neuro-Oncol., 17: 47-64, 1993.[Medline]
2. Trizna Z., de Andrade M., Kyritsis A. P., Briggs K., Levin V. A., Bruner J. M., Wei Q., Bondy M. L. Genetic polymorphisms in glutathione S-transferase mu and theta, N-acetyltransferase, and CYP1A1 and risk of gliomas.. Cancer Epidemiol. Biomark. Prev., 7: 553-555, 1998.[Abstract/Free Full Text]
3. Lee M., Wrensch M., Miike R. Dietary and tobacco risk factors for adult onset glioma in the San Francisco Bay Area (California, USA) [see comments].. Cancer Causes Control, 8: 13-24, 1997.[Medline]
4. Kelsey K. T., Wrensch M., Zuo Z. F., Miike R., Wiencke J. K. A population-based case-control study of the CYP2D6 and GSTT1 polymorphisms and malignant brain tumors.. Pharmacogenetics, 7: 463-468, 1997.[Medline]
5. Bell D. A., Taylor J. A., Butler M. A., Stephens E. A., Wiest J., Brubaker L. H., Kadlubar F. F., Lucier G. W. Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow acetylator allele common in African Americans.. Carcinogenesis (Lond.), 14: 1689-1692, 1993.[Abstract/Free Full Text]
6. Wiencke J. K., Spitz M. R., McMillan A., Kelsey K. T. Lung cancer in Mexican-Americans and African-Americans is associated with the wild-type genotype of the NAD(P)H: quinone oxidoreductase polymorphism.. Cancer Epidemiol. Biomark. Prev., 6: 87-92, 1997.[Abstract]

This article has been cited by other articles:

				H. E. Liu, P.-Y. Hsiao, C.-C. Lee, J.-A. Lee, and H.-Y. Chen NAT2*7 Allele Is a Potential Risk Factor for Adult Brain Tumors in Taiwanese Population Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 661 - 665. [Abstract] [Full Text] [PDF]

				Y. Liu, H. Zhang, K. Zhou, L. Chen, Z. Xu, Y. Zhong, H. Liu, R. Li, Y. Y. Shugart, Q. Wei, et al. Tagging SNPs in non-homologous end-joining pathway genes and risk of glioma Carcinogenesis, September 1, 2007; 28(9): 1906 - 1913. [Abstract] [Full Text] [PDF]

				J. A. Schwartzbaum, A. Ahlbom, S. Lonn, M. Warholm, A. Rannug, A. Auvinen, H. C. Christensen, R. Henriksson, C. Johansen, C. Lindholm, et al. An International Case-Control Study of Glutathione Transferase and Functionally Related Polymorphisms and Risk of Primary Adult Brain Tumors Cancer Epidemiol. Biomarkers Prev., March 1, 2007; 16(3): 559 - 565. [Abstract] [Full Text] [PDF]

				A. Begleiter, D. Hewitt, A. W. Maksymiuk, D. A. Ross, and R. P. Bird A NAD(P)H:Quinone Oxidoreductase 1 Polymorphism Is a Risk Factor for Human Colon Cancer Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2422 - 2426. [Abstract] [Full Text] [PDF]

				A. J. De Roos, N. Rothman, M. Brown, D. A. Bell, G. S. Pittman, W. R. Shapiro, R. G. Selker, H. A. Fine, P. M. Black, and P. D. Inskip Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors. Neuro-oncol, April 1, 2006; 8(2): 145 - 155. [Abstract] [Full Text] [PDF]

				M. Wrensch, Y. Minn, T. Chew, M. Bondy, and M. S. Berger Epidemiology of primary brain tumors: Current concepts and review of the literature Neuro-oncol, October 1, 2002; 4(4): 278 - 299. [Abstract] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Peters, E. S. Articles by Wrensch, M. R. Search for Related Content PubMed PubMed Citation Articles by Peters, E. S. Articles by Wrensch, M. R.