This Article Full Text Full Text (PDF) Supplementary Data 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 Cebrian, A. Articles by Ponder, B. A.J. Search for Related Content PubMed PubMed Citation Articles by Cebrian, A. Articles by Ponder, B. A.J.

Tagging Single-Nucleotide Polymorphisms in Antioxidant Defense Enzymes and Susceptibility to Breast Cancer

¹ Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, ² Cancer Research UK Genetic Epidemiology Group, and ³ Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom

Requests for reprints: Arancha Cebrian, Strangeways Research Laboratories, Worts Causeway, Cambridge CB1 8RN, United Kingdom. Phone: 44-1223-740-684; Fax: 44-1223-740-147; E-mail: arancha{at}srl.cam.ac.uk.

It is generally believed that the initiation of breast cancer is a consequence of cumulative genetic damage leading to genetic alterations and provoking uncontrolled cellular proliferation and/or aberrant programmed cell death, or apoptosis. Reactive oxygen species have been related to the etiology of cancer as they are known to be mitogenic and therefore capable of tumor promotion. The aim of this study was to assess the role of common variation in 10 polymorphic genes coding for antioxidant defense enzymes in modulating individual susceptibility to breast cancer using a case-control study (N cases = 4,474 and N controls = 4,580). Both cases and controls were from the East Anglian region of the United Kingdom. We have identified a set of 54 single nucleotide polymorphisms (SNPs) that efficiently tag all the known SNPs in the 10 genes and are also expected to tag any unknown SNPs in each gene. We found no evidence for association of common variants in SOD1, SOD2, GPX1, GPX4, GSR, TXNRD1, and TXN2. There was borderline evidence for association of variants in CAT g27168a {P [2 degrees of freedom (df)] = 0.05}, TXN t2715c [P (2 df) = 0.007], and TXNRD2 A66S and TXNRD2 g23524a (P_trend = 0.074 and 0.046, respectively). For TXNRD2 A66S [AS versus AA: odds ratio (OR), 1.05; 95% confidence intervals (95% CI), 0.96-1.15; SS versus AA: OR, 1.12; 95% CI, 0.98-1.29], there are bioinformatics data to suggest that it is functional but confirmation in independent data sets is required before they can be regarded as definitive breast cancer susceptibility alleles. Even if confirmed, these four alleles would account for just 0.32% of the excess familial risk of breast cancer. (Cancer Res 2006; 66(2): 1225-33)

This article has been cited by other articles:

				M. M. Gaudet, S. Chanock, A. Dunning, K. Driver, L. A. Brinton, J. Lissowska, B. Peplonska, P. Pharoah, and M. Garcia-Closas HSD17B1 Genetic Variants and Hormone Receptor-Defined Breast Cancer Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2766 - 2772. [Abstract] [Full Text] [PDF]

				U. Peters, N. Chatterjee, R. B. Hayes, R. E. Schoen, Y. Wang, S. J. Chanock, and C. B. Foster Variation in the Selenoenzyme Genes and Risk of Advanced Distal Colorectal Adenoma Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1144 - 1154. [Abstract] [Full Text] [PDF]

				E. D. Strome, X. Wu, M. Kimmel, and S. E. Plon Heterozygous Screen in Saccharomyces cerevisiae Identifies Dosage-Sensitive Genes That Affect Chromosome Stability Genetics, March 1, 2008; 178(3): 1193 - 1207. [Abstract] [Full Text] [PDF]

				D. Kang, K.-M. Lee, S. K. Park, S. I. Berndt, U. Peters, D. Reding, N. Chatterjee, R. Welch, S. Chanock, W.-Y. Huang, et al. Functional Variant of Manganese Superoxide Dismutase (SOD2 V16A) Polymorphism Is Associated with Prostate Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Study Cancer Epidemiol. Biomarkers Prev., August 1, 2007; 16(8): 1581 - 1586. [Abstract] [Full Text] [PDF]

				M. Udler, A.-T. Maia, A. Cebrian, C. Brown, D. Greenberg, M. Shah, C. Caldas, A. Dunning, D. Easton, B. Ponder, et al. Common Germline Genetic Variation in Antioxidant Defense Genes and Survival After Diagnosis of Breast Cancer J. Clin. Oncol., July 20, 2007; 25(21): 3015 - 3023. [Abstract] [Full Text] [PDF]

				The Breast Cancer Association Consortium Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst, October 4, 2006; 98(19): 1382 - 1396. [Abstract] [Full Text] [PDF]