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A comprehensive examination of CYP19 variation and risk of breast cancer using two haplotype-tagging approaches

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Abstract

Background

Numerous studies point to a positive relationship between elevated levels of estrogens and increased risk of breast. Androgens are converted to estrogens by the aromatase enzyme, which is encoded by the CYP19 gene. We recently published resequencing data on 88 polymorphisms identified in that gene. The hypothesis tested in this study was that polymorphisms, or haplotypes, in CYP19 are related to risk of breast cancer.

Methods

Incident cases of breast cancer were identified through the Division of Medical Oncology at the Mayo Clinic in Rochester, MN. Controls were patients visiting Mayo for an annual medical examination. Controls were frequency matched to cases based on age and region of residence. Tag-polymorphisms were selected using 2 methods: (1) 12 variants using the tag-selection method of Carlson et al. (Am J Hum Genet 74:106–120, 2004); and (2) 12 variants using the haplotype method of Stram (Genet Epidemiol 27:365–374, 2004). Six SNPs were selected by both methods. Genotyping was conducted using SNPStream, TaqMan and RFLP analyses. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Analyses were conducted among all cases and controls, or stratified by estrogen receptor alpha (ER) status and/or menopausal status.

Results

A total of 750 cases (60% postmenopausal) and 732 controls (75% postmenopausal) were included. No association with breast cancer risk was detected for individual variants, selected tagSNPs or hap-tag SNPs despite 80% power to detect OR as low as 1.49 for minor allele frequency (MAF) of 0.10. Similarly, stratified analyses based on ER status or menopausal status failed to detect any association with breast cancer risk.

Conclusion

These analyses suggest that variants of CYP19 are not associated with risk of breast cancer.

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Acknowledgements

This work was supported by grants from the National Cancer Institute P01 CA 82267, P50 CA116201 and the National Institute of General Medical Sciences R01 GM28157, R01 GM35720, and U01 GM 61388 (The Pharmacogenetics Research Network)

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Authors and Affiliations

  1. Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN , 55901, USA

    Janet E. Olson & Celine M. Vachon

  2. Department of Oncology, Division of Medical Oncology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN , 55901, USA

    James N. Ingle

  3. Division of Oncology, Siteman Comprehensive Cancer Center, Barnes–Jewish Hospital and Washington University School of Medicine, 660 South Euclid Avenue, Box 8100, St. Louis, MO, 3110-1093, USA

    Cynthia X. Ma

  4. Department of Molecular Pharmacology and Experimental Therapeutics, Division of Clinical Pharmacology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55901, USA

    Linda L. Pelleymounter & Richard M. Weinshilboum

  5. Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55901, USA

    Daniel J. Schaid, V. Shane Pankratz, Robert A. Vierkant & Zachary S. Fredericksen

  6. Genotyping Shared Resource, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55901, USA

    Yanhong Wu

  7. Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55901, USA

    Fergus J. Couch

  8. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Thomas A. Sellers

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  1. Janet E. Olson
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  2. James N. Ingle
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  3. Cynthia X. Ma
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  4. Linda L. Pelleymounter
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  5. Daniel J. Schaid
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  6. V. Shane Pankratz
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  7. Robert A. Vierkant
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  8. Zachary S. Fredericksen
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  9. Yanhong Wu
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  10. Fergus J. Couch
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  11. Celine M. Vachon
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  12. Thomas A. Sellers
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  13. Richard M. Weinshilboum
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Corresponding author

Correspondence to Janet E. Olson.

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Olson, J.E., Ingle, J.N., Ma, C.X. et al. A comprehensive examination of CYP19 variation and risk of breast cancer using two haplotype-tagging approaches. Breast Cancer Res Treat 102, 237–247 (2007). https://doi.org/10.1007/s10549-006-9324-7

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  • DOI: https://doi.org/10.1007/s10549-006-9324-7

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