Fine-mapping of the 6q25 locus identifies a novel SNP associated with breast cancer risk in African-American women

Edward A. Ruiz-Narváez, Lynn Rosenberg, Song Yao, Charles N. Rotimi, Adrienne L. Cupples, Elisa Bandera, Christine B. Ambrosone, Lucile L. Adams-Campbell, Julie R. Palmer

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Abstract

The rs2046210 single nucleotide polymorphism (SNP) in the 6q25.1 region was identified in a breast cancer genome-wide association study of Chinese women. The SNP has been replicated in European ancestry populations, but replication efforts have failed in African ancestry populations. We evaluated a total of 13 tagging SNPs in the linkage disequilibrium block around rs2046210 in a case-control study of breast cancer nested within the Black Women's Health Study, which included 1191 cases and 1941 controls. Replication of initial significant findings was carried out in 665 cases and 821 controls of African ancestry from the Women's Circle of Health Study (WCHS). No significant association was found for rs2046210 in univariate analysis. A new SNP, rs2046211, was significantly associated with reduced risk of breast cancer and was replicated in data from WCHS. In joint analyses that included both SNPs, the rs2046210-A allele was associated with increased risk of breast cancer [odds ratio (OR) = 1.14; 95% confidence interval (CI) = 1.02-1.28], and the rs2046211-G allele was associated with reduced risk (OR = 0.80; 95% CI = 0.67- 0.95). Haplotype analysis confirmed these results and showed that the rs2046210-A allele is present in high-risk (rs2046211-C/ rs2046210-A) and low-risk (rs2046211-G/rs2046210-A) haplotypes. Our results confirm the importance of 6q25.1 as a breast cancer susceptibility region. We replicated the rs2046210 association, after accounting for the haplotype background that included rs2046211 in African-American women, and we report the presence of a novel signal that is tagged by rs2046211.

Original languageEnglish (US)
Pages (from-to)287-291
Number of pages5
JournalCarcinogenesis
Volume34
Issue number2
DOIs
StatePublished - Feb 1 2013

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African Americans
Single Nucleotide Polymorphism
Breast Neoplasms
Women's Health
Haplotypes
Alleles
Odds Ratio
Confidence Intervals
Genome-Wide Association Study
Linkage Disequilibrium
Population
Case-Control Studies
Joints

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Ruiz-Narváez, E. A., Rosenberg, L., Yao, S., Rotimi, C. N., Cupples, A. L., Bandera, E., ... Palmer, J. R. (2013). Fine-mapping of the 6q25 locus identifies a novel SNP associated with breast cancer risk in African-American women. Carcinogenesis, 34(2), 287-291. https://doi.org/10.1093/carcin/bgs334
Ruiz-Narváez, Edward A. ; Rosenberg, Lynn ; Yao, Song ; Rotimi, Charles N. ; Cupples, Adrienne L. ; Bandera, Elisa ; Ambrosone, Christine B. ; Adams-Campbell, Lucile L. ; Palmer, Julie R. / Fine-mapping of the 6q25 locus identifies a novel SNP associated with breast cancer risk in African-American women. In: Carcinogenesis. 2013 ; Vol. 34, No. 2. pp. 287-291.
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abstract = "The rs2046210 single nucleotide polymorphism (SNP) in the 6q25.1 region was identified in a breast cancer genome-wide association study of Chinese women. The SNP has been replicated in European ancestry populations, but replication efforts have failed in African ancestry populations. We evaluated a total of 13 tagging SNPs in the linkage disequilibrium block around rs2046210 in a case-control study of breast cancer nested within the Black Women's Health Study, which included 1191 cases and 1941 controls. Replication of initial significant findings was carried out in 665 cases and 821 controls of African ancestry from the Women's Circle of Health Study (WCHS). No significant association was found for rs2046210 in univariate analysis. A new SNP, rs2046211, was significantly associated with reduced risk of breast cancer and was replicated in data from WCHS. In joint analyses that included both SNPs, the rs2046210-A allele was associated with increased risk of breast cancer [odds ratio (OR) = 1.14; 95{\%} confidence interval (CI) = 1.02-1.28], and the rs2046211-G allele was associated with reduced risk (OR = 0.80; 95{\%} CI = 0.67- 0.95). Haplotype analysis confirmed these results and showed that the rs2046210-A allele is present in high-risk (rs2046211-C/ rs2046210-A) and low-risk (rs2046211-G/rs2046210-A) haplotypes. Our results confirm the importance of 6q25.1 as a breast cancer susceptibility region. We replicated the rs2046210 association, after accounting for the haplotype background that included rs2046211 in African-American women, and we report the presence of a novel signal that is tagged by rs2046211.",
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Ruiz-Narváez, EA, Rosenberg, L, Yao, S, Rotimi, CN, Cupples, AL, Bandera, E, Ambrosone, CB, Adams-Campbell, LL & Palmer, JR 2013, 'Fine-mapping of the 6q25 locus identifies a novel SNP associated with breast cancer risk in African-American women', Carcinogenesis, vol. 34, no. 2, pp. 287-291. https://doi.org/10.1093/carcin/bgs334

Fine-mapping of the 6q25 locus identifies a novel SNP associated with breast cancer risk in African-American women. / Ruiz-Narváez, Edward A.; Rosenberg, Lynn; Yao, Song; Rotimi, Charles N.; Cupples, Adrienne L.; Bandera, Elisa; Ambrosone, Christine B.; Adams-Campbell, Lucile L.; Palmer, Julie R.

In: Carcinogenesis, Vol. 34, No. 2, 01.02.2013, p. 287-291.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fine-mapping of the 6q25 locus identifies a novel SNP associated with breast cancer risk in African-American women

AU - Ruiz-Narváez, Edward A.

AU - Rosenberg, Lynn

AU - Yao, Song

AU - Rotimi, Charles N.

AU - Cupples, Adrienne L.

AU - Bandera, Elisa

AU - Ambrosone, Christine B.

AU - Adams-Campbell, Lucile L.

AU - Palmer, Julie R.

PY - 2013/2/1

Y1 - 2013/2/1

N2 - The rs2046210 single nucleotide polymorphism (SNP) in the 6q25.1 region was identified in a breast cancer genome-wide association study of Chinese women. The SNP has been replicated in European ancestry populations, but replication efforts have failed in African ancestry populations. We evaluated a total of 13 tagging SNPs in the linkage disequilibrium block around rs2046210 in a case-control study of breast cancer nested within the Black Women's Health Study, which included 1191 cases and 1941 controls. Replication of initial significant findings was carried out in 665 cases and 821 controls of African ancestry from the Women's Circle of Health Study (WCHS). No significant association was found for rs2046210 in univariate analysis. A new SNP, rs2046211, was significantly associated with reduced risk of breast cancer and was replicated in data from WCHS. In joint analyses that included both SNPs, the rs2046210-A allele was associated with increased risk of breast cancer [odds ratio (OR) = 1.14; 95% confidence interval (CI) = 1.02-1.28], and the rs2046211-G allele was associated with reduced risk (OR = 0.80; 95% CI = 0.67- 0.95). Haplotype analysis confirmed these results and showed that the rs2046210-A allele is present in high-risk (rs2046211-C/ rs2046210-A) and low-risk (rs2046211-G/rs2046210-A) haplotypes. Our results confirm the importance of 6q25.1 as a breast cancer susceptibility region. We replicated the rs2046210 association, after accounting for the haplotype background that included rs2046211 in African-American women, and we report the presence of a novel signal that is tagged by rs2046211.

AB - The rs2046210 single nucleotide polymorphism (SNP) in the 6q25.1 region was identified in a breast cancer genome-wide association study of Chinese women. The SNP has been replicated in European ancestry populations, but replication efforts have failed in African ancestry populations. We evaluated a total of 13 tagging SNPs in the linkage disequilibrium block around rs2046210 in a case-control study of breast cancer nested within the Black Women's Health Study, which included 1191 cases and 1941 controls. Replication of initial significant findings was carried out in 665 cases and 821 controls of African ancestry from the Women's Circle of Health Study (WCHS). No significant association was found for rs2046210 in univariate analysis. A new SNP, rs2046211, was significantly associated with reduced risk of breast cancer and was replicated in data from WCHS. In joint analyses that included both SNPs, the rs2046210-A allele was associated with increased risk of breast cancer [odds ratio (OR) = 1.14; 95% confidence interval (CI) = 1.02-1.28], and the rs2046211-G allele was associated with reduced risk (OR = 0.80; 95% CI = 0.67- 0.95). Haplotype analysis confirmed these results and showed that the rs2046210-A allele is present in high-risk (rs2046211-C/ rs2046210-A) and low-risk (rs2046211-G/rs2046210-A) haplotypes. Our results confirm the importance of 6q25.1 as a breast cancer susceptibility region. We replicated the rs2046210 association, after accounting for the haplotype background that included rs2046211 in African-American women, and we report the presence of a novel signal that is tagged by rs2046211.

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