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Epidemiology 7: DNA Repair Genotype/Phenotype I

DNA repair gene polymorphisms and the risk of breast cancer: The Iowa Women’s Health Study (IWHS)

Bharat Thyagarajan, Waseem Khaliq, Kristin E. Anderson, David R. Jacobs, Archana Bargaje, Aaron R. Folsom, Charles Lynch, Freda Selk and Myron D. Gross
Bharat Thyagarajan
University of Minnesota, Minneapolis, MN and University of Iowa, Iowa City, IA
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Waseem Khaliq
University of Minnesota, Minneapolis, MN and University of Iowa, Iowa City, IA
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Kristin E. Anderson
University of Minnesota, Minneapolis, MN and University of Iowa, Iowa City, IA
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David R. Jacobs
University of Minnesota, Minneapolis, MN and University of Iowa, Iowa City, IA
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Archana Bargaje
University of Minnesota, Minneapolis, MN and University of Iowa, Iowa City, IA
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Aaron R. Folsom
University of Minnesota, Minneapolis, MN and University of Iowa, Iowa City, IA
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Charles Lynch
University of Minnesota, Minneapolis, MN and University of Iowa, Iowa City, IA
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Freda Selk
University of Minnesota, Minneapolis, MN and University of Iowa, Iowa City, IA
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Myron D. Gross
University of Minnesota, Minneapolis, MN and University of Iowa, Iowa City, IA
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DOI:  Published April 2004
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Proc Amer Assoc Cancer Res, Volume 45, 2004

Abstract

2896

Decreased DNA repair activity has been associated with an increased risk of several cancers and may be a risk factor for breast cancer. It can be influenced by genetic polymorphisms in DNA repair genes. Genetic polymorphisms in one of the DNA repair pathways, nucleotide excision repair, were evaluated for associations with the risk of breast cancer in the IWHS cohort. The genes, exons, and polymorphism positions (Genbank) included XPD-23 (A35931C) and XPG-15 (C3507G). A nested case-control study was conducted in a 41,836 postmenopausal women in Iowa followed prospectively. Demographic and reproductive history information was obtained at baseline in 1986. Tissue samples (blood and paraffin-embedded blocks) from available incident cases (460) between 1992 and 1996 and blood from randomly selected population-based cancer-free controls (332) were collected and analyzed. Genotype frequencies differed between cases and controls for XPD 23 (P< 0.0002), but not XPG-15 (P<0.61). The odds ratio of breast cancer and (confidence limits) for the CC plus CA vs. AA genotype of XPD-23 was 0.57 (0.42-0.76, p<0.0002) and for CC plus GC vs. GG of XPG-15 was 0.92 (0.68-1.25, p = 0.61). Thus, a genetic polymorphism in a nucleotide excision pathway gene, XPD, was associated with a reduced risk of breast cancer in a population of postmenopausal women. Previously, XPD-23 (C) was associated with increased levels of DNA repair activity as compared to XPD-23 (A). These results suggest an influence of a nucleotide excision gene on the risk of sporadic breast cancer. A comprehensive analysis of DNA repair genes may aid in the identification of a basis for the genetic susceptibility to breast cancer. Supported by R01-CA39742

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April 2004
Volume 64, Issue 7 Supplement
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DNA repair gene polymorphisms and the risk of breast cancer: The Iowa Women’s Health Study (IWHS)
Bharat Thyagarajan, Waseem Khaliq, Kristin E. Anderson, David R. Jacobs, Archana Bargaje, Aaron R. Folsom, Charles Lynch, Freda Selk and Myron D. Gross
Cancer Res April 1 2004 (64) (7 Supplement) 668;

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DNA repair gene polymorphisms and the risk of breast cancer: The Iowa Women’s Health Study (IWHS)
Bharat Thyagarajan, Waseem Khaliq, Kristin E. Anderson, David R. Jacobs, Archana Bargaje, Aaron R. Folsom, Charles Lynch, Freda Selk and Myron D. Gross
Cancer Res April 1 2004 (64) (7 Supplement) 668;
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