Fine-Mapping CASP8 Risk Variants in Breast Cancer
- 1 January 2012
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Epidemiology, Biomarkers & Prevention
- Vol. 21 (1), 176-181
- https://doi.org/10.1158/1055-9965.epi-11-0845
Abstract
Background: Multiple genome-wide and candidate gene association studies have been conducted in search of common risk variants for breast cancer. Recent large meta analyses, consolidating evidence from these studies, have been consistent in highlighting the caspase-8 (CASP8) gene as important in this regard. To define a risk haplotype and map the CASP8 gene region with respect to underlying susceptibility variant/s, we screened four genes in the CASP8 region on 2q33-q34 for breast cancer risk. Methods: Two independent data sets from the United Kingdom and the United States, including 3,888 breast cancer cases and controls, were genotyped for 45 tagging single nucleotide polymorphisms (tSNP) in the expanded CASP8 region. SNP and haplotype association tests were carried out using Monte Carlo-based methods. Results: We identified a three-SNP haplotype across rs3834129, rs6723097, and rs3817578 that was significantly associated with breast cancer (P < 5 × 10−6), with a dominant risk ratio and 95% CI of 1.28 (1.21–1.35) and frequency of 0.29 in controls. Evidence for this risk haplotype was extremely consistent across the two study sites and also consistent with previous data. Conclusion: This three-SNP risk haplotype represents the best characterization so far of the chromosome upon which the susceptibility variant resides. Impact: Characterization of the risk haplotype provides a strong foundation for resequencing efforts to identify the underlying risk variant, which may prove useful for individual-level risk prediction, and provide novel insights into breast carcinogenesis. Cancer Epidemiol Biomarkers Prev; 21(1); 176–81. ©2011 AACR.Keywords
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This publication has 19 references indexed in Scilit:
- Genome-wide association study identifies three new melanoma susceptibility lociNature Genetics, 2011
- Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidenceThe Lancet Oncology, 2011
- Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studiesBreast Cancer Research and Treatment, 2011
- CASP8 polymorphisms contribute to cancer susceptibility: evidence from a meta-analysis of 23 publications with 55 individual studiesCarcinogenesis: Integrative Cancer Research, 2010
- The Six-Nucleotide Deletion/Insertion Variant in the CASP8 Promoter Region Is Inversely Associated with Risk of Squamous Cell Carcinoma of the Head and NeckCancer Prevention Research, 2010
- Association of Breast Cancer Susceptibility Variants with Risk of Pancreatic CancerCancer Epidemiology, Biomarkers & Prevention, 2009
- A common coding variant in CASP8 is associated with breast cancer riskNature Genetics, 2007
- Association of the CASP10 V410I variant with reduced familial breast cancer risk and interaction with the CASP8 D302H variantCarcinogenesis: Integrative Cancer Research, 2005
- Association of a Common Variant of the CASP8 Gene With Reduced Risk of Breast CancerJNCI Journal of the National Cancer Institute, 2004
- Selecting a Maximally Informative Set of Single-Nucleotide Polymorphisms for Association Analyses Using Linkage DisequilibriumAmerican Journal of Human Genetics, 2004