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Association of theProgesterone ReceptorGene with Breast Cancer Risk: A Single-Nucleotide Polymorphism Tagging Approach
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| Zeitschriftentitel: | Cancer Epidemiology, Biomarkers & Prevention |
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| Personen und Körperschaften: | , , , , , , , , , , |
| In: | Cancer Epidemiology, Biomarkers & Prevention, 15, 2006, 4, S. 675-682 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title><jats:p>Association studies on susceptibility to breast cancer using single nucleotide polymorphisms (SNP) in the progesterone receptor (PGR) gene have been previously published, but the results have been inconclusive. We used a comprehensive SNP-tagging approach to search for low-penetrance susceptibility alleles in a study of up to 4,647 cases and 4,564 controls, in a two-stage study design. We identified seven tagging SNPs using genotype data from the National Institute of Environmental Health Sciences (NIEHS) Environmental Genome Project and typed these, and an additional three SNPs, in 2,345 breast cancer cases and 2,284 controls (set 1). Three SNPs showed no evidence for association and were not studied further, whereas seven SNPs (rs11571171, rs7116336, rs660149, rs10895068, rs500760, rs566351, and rs1042838) exhibited significant associations at P &lt; 0.1 using either a heterogeneity or trend test and progressed to be genotyped in set 2. After both stages, only one SNP was significantly associated with an increased risk of breast cancer — the PGR-12 (rs1042638) V660L valine to leucine polymorphism [VL heterozygotes (odds ratio, 1.13; 95% confidence interval, 1.03-1.24) and the LL homozygotes (odds ratio, 1.30; 95% confidence interval, 0.98-1.73), Phet = 0.008, Ptrend = 0.002]. Similar estimates were obtained in a combined analysis of our data with those from three other published studies. We conclude that the 660L allele may be associated with a moderately increased risk of breast cancer, but that other common SNPs in the PGR gene are unlikely to be associated with a substantial risk of breast cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(4):675–82)</jats:p> |
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| Umfang: | 675-682 |
| ISSN: |
1055-9965
1538-7755 |
| DOI: | 10.1158/1055-9965.epi-05-0679 |