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Epidemiology and Prevention

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

Arancha Cebrian, Paul D. Pharoah, Shahana Ahmed, Paula L. Smith, Craig Luccarini, Robert Luben, Karen Redman, Hannah Munday, Douglas F. Easton, Alison M. Dunning and Bruce A.J. Ponder
Arancha Cebrian
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Paul D. Pharoah
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Shahana Ahmed
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Paula L. Smith
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Craig Luccarini
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Robert Luben
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Karen Redman
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Hannah Munday
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Douglas F. Easton
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Alison M. Dunning
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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Bruce A.J. Ponder
1Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, University of Cambridge, 2Cancer Research UK Genetic Epidemiology Group, and 3Department of Public Health and Primary Care, Strangeways Research Laboratories, Cambridge, United Kingdom
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DOI: 10.1158/0008-5472.CAN-05-1857 Published January 2006
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Abstract

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 (Ptrend = 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)

  • Tag SNP
  • oxidative stress
  • antioxidant enzyme
  • susceptibility
  • breast cancer
  • Received May 27, 2005.
  • Revision received September 23, 2005.
  • Accepted November 11, 2005.
  • ©2006 American Association for Cancer Research.
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Cancer Research: 66 (2)
January 2006
Volume 66, Issue 2
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Tagging Single-Nucleotide Polymorphisms in Antioxidant Defense Enzymes and Susceptibility to Breast Cancer
Arancha Cebrian, Paul D. Pharoah, Shahana Ahmed, Paula L. Smith, Craig Luccarini, Robert Luben, Karen Redman, Hannah Munday, Douglas F. Easton, Alison M. Dunning and Bruce A.J. Ponder
Cancer Res January 15 2006 (66) (2) 1225-1233; DOI: 10.1158/0008-5472.CAN-05-1857

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Tagging Single-Nucleotide Polymorphisms in Antioxidant Defense Enzymes and Susceptibility to Breast Cancer
Arancha Cebrian, Paul D. Pharoah, Shahana Ahmed, Paula L. Smith, Craig Luccarini, Robert Luben, Karen Redman, Hannah Munday, Douglas F. Easton, Alison M. Dunning and Bruce A.J. Ponder
Cancer Res January 15 2006 (66) (2) 1225-1233; DOI: 10.1158/0008-5472.CAN-05-1857
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Keywords

  • Tag SNP
  • oxidative stress
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