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A Breast Cancer Risk Haplotype in the Caspase-8 Gene
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| Zeitschriftentitel: | Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , |
| In: | Cancer Research, 69, 2009, 7, S. 2724-2728 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Shephard, Neil Duncan Abo, Ryan Rigas, Sushila Harkisandas Frank, Bernd Lin, Wei-Yu Brock, Ian Wallace Shippen, Adam Balasubramanian, Sabapathy Prakash Reed, Malcolm Walter Ronald Bartram, Claus Rainer Meindl, Alfons Schmutzler, Rita Katharina Engel, Christoph Burwinkel, Barbara Cannon-Albright, Lisa Anne Allen-Brady, Kristina Camp, Nicola Jane Cox, Angela Shephard, Neil Duncan Abo, Ryan Rigas, Sushila Harkisandas Frank, Bernd Lin, Wei-Yu Brock, Ian Wallace Shippen, Adam Balasubramanian, Sabapathy Prakash Reed, Malcolm Walter Ronald Bartram, Claus Rainer Meindl, Alfons Schmutzler, Rita Katharina Engel, Christoph Burwinkel, Barbara Cannon-Albright, Lisa Anne Allen-Brady, Kristina Camp, Nicola Jane Cox, Angela |
|---|---|
| author |
Shephard, Neil Duncan Abo, Ryan Rigas, Sushila Harkisandas Frank, Bernd Lin, Wei-Yu Brock, Ian Wallace Shippen, Adam Balasubramanian, Sabapathy Prakash Reed, Malcolm Walter Ronald Bartram, Claus Rainer Meindl, Alfons Schmutzler, Rita Katharina Engel, Christoph Burwinkel, Barbara Cannon-Albright, Lisa Anne Allen-Brady, Kristina Camp, Nicola Jane Cox, Angela |
| spellingShingle |
Shephard, Neil Duncan Abo, Ryan Rigas, Sushila Harkisandas Frank, Bernd Lin, Wei-Yu Brock, Ian Wallace Shippen, Adam Balasubramanian, Sabapathy Prakash Reed, Malcolm Walter Ronald Bartram, Claus Rainer Meindl, Alfons Schmutzler, Rita Katharina Engel, Christoph Burwinkel, Barbara Cannon-Albright, Lisa Anne Allen-Brady, Kristina Camp, Nicola Jane Cox, Angela Cancer Research A Breast Cancer Risk Haplotype in the Caspase-8 Gene Cancer Research Oncology |
| author_sort |
shephard, neil duncan |
| spelling |
Shephard, Neil Duncan Abo, Ryan Rigas, Sushila Harkisandas Frank, Bernd Lin, Wei-Yu Brock, Ian Wallace Shippen, Adam Balasubramanian, Sabapathy Prakash Reed, Malcolm Walter Ronald Bartram, Claus Rainer Meindl, Alfons Schmutzler, Rita Katharina Engel, Christoph Burwinkel, Barbara Cannon-Albright, Lisa Anne Allen-Brady, Kristina Camp, Nicola Jane Cox, Angela 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-08-4266 <jats:title>Abstract</jats:title> <jats:p>Recent large-scale studies have been successful in identifying common, low-penetrance variants associated with common cancers. One such variant in the caspase-8 (CASP8) gene, D302H (rs1045485), has been confirmed to be associated with breast cancer risk, although the functional effect of this polymorphism (if any) is not yet clear. In order to further map the CASP8 gene with respect to breast cancer susceptibility, we performed extensive haplotype analyses using single nucleotide polymorphisms (SNP) chosen to tag all common variations in the gene (tSNP). We used a staged study design based on 3,200 breast cancer and 3,324 control subjects from the United Kingdom, Utah, and Germany. Using a haplotype-mining algorithm in the UK cohort, we identified a four-SNP haplotype that was significantly associated with breast cancer and that was superior to any other single or multi-locus combination (P = 8.0 × 10−5), with a per allele odds ratio and 95% confidence interval of 1.30 (1.12–1.49). The result remained significant after adjustment for the multiple testing inherent in mining techniques (false discovery rate, q = 0.044). As expected, this haplotype includes the D302H locus. Multicenter analyses on a subset of the tSNPs yielded consistent results. This risk haplotype is likely to carry one or more underlying breast cancer susceptibility alleles, making it an excellent candidate for resequencing in homozygous individuals. An understanding of the mode of action of these alleles will aid risk assessment and may lead to the identification of novel treatment targets in breast cancer. [Cancer Res 2009;69(7):2724–8]</jats:p> A Breast Cancer Risk Haplotype in the Caspase-8 Gene Cancer Research |
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10.1158/0008-5472.can-08-4266 |
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| title |
A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_unstemmed |
A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_full |
A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_fullStr |
A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_full_unstemmed |
A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_short |
A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_sort |
a breast cancer risk haplotype in the caspase-8 gene |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/0008-5472.can-08-4266 |
| publishDate |
2009 |
| physical |
2724-2728 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Recent large-scale studies have been successful in identifying common, low-penetrance variants associated with common cancers. One such variant in the caspase-8 (CASP8) gene, D302H (rs1045485), has been confirmed to be associated with breast cancer risk, although the functional effect of this polymorphism (if any) is not yet clear. In order to further map the CASP8 gene with respect to breast cancer susceptibility, we performed extensive haplotype analyses using single nucleotide polymorphisms (SNP) chosen to tag all common variations in the gene (tSNP). We used a staged study design based on 3,200 breast cancer and 3,324 control subjects from the United Kingdom, Utah, and Germany. Using a haplotype-mining algorithm in the UK cohort, we identified a four-SNP haplotype that was significantly associated with breast cancer and that was superior to any other single or multi-locus combination (P = 8.0 × 10−5), with a per allele odds ratio and 95% confidence interval of 1.30 (1.12–1.49). The result remained significant after adjustment for the multiple testing inherent in mining techniques (false discovery rate, q = 0.044). As expected, this haplotype includes the D302H locus. Multicenter analyses on a subset of the tSNPs yielded consistent results. This risk haplotype is likely to carry one or more underlying breast cancer susceptibility alleles, making it an excellent candidate for resequencing in homozygous individuals. An understanding of the mode of action of these alleles will aid risk assessment and may lead to the identification of novel treatment targets in breast cancer. [Cancer Res 2009;69(7):2724–8]</jats:p> |
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| author | Shephard, Neil Duncan, Abo, Ryan, Rigas, Sushila Harkisandas, Frank, Bernd, Lin, Wei-Yu, Brock, Ian Wallace, Shippen, Adam, Balasubramanian, Sabapathy Prakash, Reed, Malcolm Walter Ronald, Bartram, Claus Rainer, Meindl, Alfons, Schmutzler, Rita Katharina, Engel, Christoph, Burwinkel, Barbara, Cannon-Albright, Lisa Anne, Allen-Brady, Kristina, Camp, Nicola Jane, Cox, Angela |
| author_facet | Shephard, Neil Duncan, Abo, Ryan, Rigas, Sushila Harkisandas, Frank, Bernd, Lin, Wei-Yu, Brock, Ian Wallace, Shippen, Adam, Balasubramanian, Sabapathy Prakash, Reed, Malcolm Walter Ronald, Bartram, Claus Rainer, Meindl, Alfons, Schmutzler, Rita Katharina, Engel, Christoph, Burwinkel, Barbara, Cannon-Albright, Lisa Anne, Allen-Brady, Kristina, Camp, Nicola Jane, Cox, Angela, Shephard, Neil Duncan, Abo, Ryan, Rigas, Sushila Harkisandas, Frank, Bernd, Lin, Wei-Yu, Brock, Ian Wallace, Shippen, Adam, Balasubramanian, Sabapathy Prakash, Reed, Malcolm Walter Ronald, Bartram, Claus Rainer, Meindl, Alfons, Schmutzler, Rita Katharina, Engel, Christoph, Burwinkel, Barbara, Cannon-Albright, Lisa Anne, Allen-Brady, Kristina, Camp, Nicola Jane, Cox, Angela |
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| description | <jats:title>Abstract</jats:title> <jats:p>Recent large-scale studies have been successful in identifying common, low-penetrance variants associated with common cancers. One such variant in the caspase-8 (CASP8) gene, D302H (rs1045485), has been confirmed to be associated with breast cancer risk, although the functional effect of this polymorphism (if any) is not yet clear. In order to further map the CASP8 gene with respect to breast cancer susceptibility, we performed extensive haplotype analyses using single nucleotide polymorphisms (SNP) chosen to tag all common variations in the gene (tSNP). We used a staged study design based on 3,200 breast cancer and 3,324 control subjects from the United Kingdom, Utah, and Germany. Using a haplotype-mining algorithm in the UK cohort, we identified a four-SNP haplotype that was significantly associated with breast cancer and that was superior to any other single or multi-locus combination (P = 8.0 × 10−5), with a per allele odds ratio and 95% confidence interval of 1.30 (1.12–1.49). The result remained significant after adjustment for the multiple testing inherent in mining techniques (false discovery rate, q = 0.044). As expected, this haplotype includes the D302H locus. Multicenter analyses on a subset of the tSNPs yielded consistent results. This risk haplotype is likely to carry one or more underlying breast cancer susceptibility alleles, making it an excellent candidate for resequencing in homozygous individuals. An understanding of the mode of action of these alleles will aid risk assessment and may lead to the identification of novel treatment targets in breast cancer. [Cancer Res 2009;69(7):2724–8]</jats:p> |
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| spelling | Shephard, Neil Duncan Abo, Ryan Rigas, Sushila Harkisandas Frank, Bernd Lin, Wei-Yu Brock, Ian Wallace Shippen, Adam Balasubramanian, Sabapathy Prakash Reed, Malcolm Walter Ronald Bartram, Claus Rainer Meindl, Alfons Schmutzler, Rita Katharina Engel, Christoph Burwinkel, Barbara Cannon-Albright, Lisa Anne Allen-Brady, Kristina Camp, Nicola Jane Cox, Angela 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-08-4266 <jats:title>Abstract</jats:title> <jats:p>Recent large-scale studies have been successful in identifying common, low-penetrance variants associated with common cancers. One such variant in the caspase-8 (CASP8) gene, D302H (rs1045485), has been confirmed to be associated with breast cancer risk, although the functional effect of this polymorphism (if any) is not yet clear. In order to further map the CASP8 gene with respect to breast cancer susceptibility, we performed extensive haplotype analyses using single nucleotide polymorphisms (SNP) chosen to tag all common variations in the gene (tSNP). We used a staged study design based on 3,200 breast cancer and 3,324 control subjects from the United Kingdom, Utah, and Germany. Using a haplotype-mining algorithm in the UK cohort, we identified a four-SNP haplotype that was significantly associated with breast cancer and that was superior to any other single or multi-locus combination (P = 8.0 × 10−5), with a per allele odds ratio and 95% confidence interval of 1.30 (1.12–1.49). The result remained significant after adjustment for the multiple testing inherent in mining techniques (false discovery rate, q = 0.044). As expected, this haplotype includes the D302H locus. Multicenter analyses on a subset of the tSNPs yielded consistent results. This risk haplotype is likely to carry one or more underlying breast cancer susceptibility alleles, making it an excellent candidate for resequencing in homozygous individuals. An understanding of the mode of action of these alleles will aid risk assessment and may lead to the identification of novel treatment targets in breast cancer. [Cancer Res 2009;69(7):2724–8]</jats:p> A Breast Cancer Risk Haplotype in the Caspase-8 Gene Cancer Research |
| spellingShingle | Shephard, Neil Duncan, Abo, Ryan, Rigas, Sushila Harkisandas, Frank, Bernd, Lin, Wei-Yu, Brock, Ian Wallace, Shippen, Adam, Balasubramanian, Sabapathy Prakash, Reed, Malcolm Walter Ronald, Bartram, Claus Rainer, Meindl, Alfons, Schmutzler, Rita Katharina, Engel, Christoph, Burwinkel, Barbara, Cannon-Albright, Lisa Anne, Allen-Brady, Kristina, Camp, Nicola Jane, Cox, Angela, Cancer Research, A Breast Cancer Risk Haplotype in the Caspase-8 Gene, Cancer Research, Oncology |
| title | A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_full | A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_fullStr | A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_full_unstemmed | A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_short | A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| title_sort | a breast cancer risk haplotype in the caspase-8 gene |
| title_unstemmed | A Breast Cancer Risk Haplotype in the Caspase-8 Gene |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/0008-5472.can-08-4266 |