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Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States

  • Epidemiology
  • Published:
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Abstract

Genome-wide association studies (GWAS) have identified several loci as being associated with breast cancer in mostly European populations. We focus on TNRC9 rs3803662, FGFR2 rs1219648 and rs2981582, MAP3K1 rs889312, and 2q35 rs13387042, to replicate in the 4-Corner’s Breast Cancer Study of Hispanic (N = 565 cases and 714 controls) and non-Hispanic white (NHW) women (N = 1177 cases and 1330 controls). We evaluate associations by ethnicity, menopausal status, and tumor ER/PR status after adjusting for genetic admixture. TNRC9 AA genotype was associated with significant increased risk among NHW women (OR 1.54, 95% CI 1.14, 2.08; P trend 0.003). Both polymorphisms of FGFR2 were associated with statistically significant increased risk for NHW and Hispanic women; MAP3K1 was not associated with risk among either ethnic group. The polymorphism on 2q35 was associated with a statistically significant increased risk among Hispanic women (OR 1.53, 95% CI 1.08, 2.15 for the AA genotype; P trend = 0.004). Associations were significantly different among pre/peri-menopausal women for TNRC9 (P heterogeneity 0.008) and for 2q35 (P heterogeneity 0.08) for NHW and Hispanic women. Both FGFR2 polymorphisms reduced risk of ER−/PR− tumors in the presence of the minor allele among NHW women. Among Hispanic women, polymorphisms of the FGFR2 gene were associated with almost a twofold increase risk of an ER+/PR+ tumor, while non-significantly inversely associated with ER−/PR− tumors. Our data replicated some of the previously reported GWAS findings. Differences in associations were detected for NHW and Hispanic women by menopausal status and by ER/PR status of tumors.

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Abbreviations

NHW:

Non-Hispanic white

OR:

Odds ratios

CI:

Confidence intervals

ER:

Estrogen receptor

PR:

Progesterone receptor

GWAS:

Genome-wide association study

MAP:

Mitogen-activated protein

FGFR:

Fibroblast growth factor receptor

TRNC9:

Trinucleotide repeat-containing 9

GUESS:

Generally useful ethnic search system

AI:

American Indian

SNP:

Single nucleotide polymorphism

HWE:

Hardy–Weinberg Equilibrium

MAF:

Minor allele frequency

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Acknowledgments

CA 078682, CA 078762, CA078552, CA078802, and CA14002. This research also was supported by the Utah Cancer Registry, which is funded by Contract #N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health, the New Mexico Tumor Registry, funded by contract #, and the Arizona and Colorado cancer registries, funded by the Centers for Disease Control and Prevention National Program of Cancer Registries and additional state support. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute. We would like to acknowledge the contributions of Dr. Betsy Risendal, Sandra Edwards, Roger Edwards, Leslie Palmer, Tara Patton, Jason Witter, and Kelly May to this study.

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Authors and Affiliations

  1. University of Utah, Salt Lake City, UT, 84108, USA

    Martha L. Slattery, Jennifer S. Herrick & Roger K. Wolff

  2. Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, USA

    Kathy B. Baumgartner

  3. Moffitt Cancer Center, Tampa, FL, USA

    Anna R. Giuliano

  4. University of Colorado School of Medicine, Denver, CO, USA

    Tim Byers

Authors
  1. Martha L. Slattery
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  2. Kathy B. Baumgartner
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  3. Anna R. Giuliano
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  4. Tim Byers
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  5. Jennifer S. Herrick
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  6. Roger K. Wolff
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Correspondence to Martha L. Slattery.

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Slattery, M.L., Baumgartner, K.B., Giuliano, A.R. et al. Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States. Breast Cancer Res Treat 129, 531–539 (2011). https://doi.org/10.1007/s10549-011-1498-y

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  • DOI: https://doi.org/10.1007/s10549-011-1498-y

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