Breast Cancer Research and Treatment

, Volume 114, Issue 3, pp 463–477 | Cite as

A pilot genome-wide association study of early-onset breast cancer

  • Muhammad G. Kibriya
  • Farzana Jasmine
  • Maria Argos
  • Irene L. Andrulis
  • Esther M. John
  • Jenny Chang-Claude
  • Habibul Ahsan
Preclinical Study

Abstract

High-density oligonucleotide microarrays containing a large number of single nucleotide polymorphisms (SNPs) have enabled genome-wide association (GWA) analysis to become a reality. We used the early access Affymetrix Mendel Nsp 250K chips in a GWA case–control pilot study to identify genomic regions associated with breast cancer. We included 30 randomly sampled incident invasive breast cancer cases aged <45 years without deleterious mutations in the BRCA1 or BRCA2 genes, and 30 population controls individually matched on age, ethnicity and geographical area. The overall genotype call rate was 97.13 ± 1.33% for controls and 97.48 ± 1.42% for cases. Comparison was made between cases and controls for 203,477 genotyped SNPs using (a) unconditional logistic regression (ULR), (b) conditional logistic regression (CLR) models with adjustment for the matched pairs, (c) allelic tests for single marker tests and (d) haplotype trend regression (HTR). Genomic control and EIGENSTRAT methods were used for correction of population stratification in appropriate models. We demonstrate the similarity and dissimilarity of results from different statistical analyses. We found several possible significant regions harboring biologically meaningful known candidate genes, such as genes encoding fibroblast growth factor, transforming growth factor, epidermal growth factor, and estrogen synthesis enzymes to be associated with early-onset breast cancer. In single marker analysis, none of the SNPs were statistically significant after correction for multiple testing. However, haplotype association tests, using 90730 tag-SNPs, suggested two regions in GLG1 and UGT1 genes retaining significance even after Bonferroni correction. Nevertheless, without systematic replication, findings from this pilot study, especially the associations of breast cancer in relation to specific SNPs, should be interpreted with great caution.

Keywords

Genome-wide association Breast cancer Microarray Affymetrix GeneChip Genome scan 

Abbreviations

SNP

Single nucleotide polymorphism

GWA

Genome-wide association

LD

Linkage disequilibrium

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Muhammad G. Kibriya
    • 1
  • Farzana Jasmine
    • 1
  • Maria Argos
    • 1
  • Irene L. Andrulis
    • 2
    • 3
  • Esther M. John
    • 4
    • 5
  • Jenny Chang-Claude
    • 6
  • Habibul Ahsan
    • 1
    • 7
    • 8
    • 9
  1. 1.Department of Health StudiesThe University of ChicagoChicagoUSA
  2. 2.Samuel Lunenfeld Research Institute, Mount Sinai HospitalTorontoCanada
  3. 3.Department of Molecular GeneticsUniversity of TorontoTorontoCanada
  4. 4.Northern California Cancer CenterFremontUSA
  5. 5.Department of Health Research and PolicyStanford School of MedicineStanfordUSA
  6. 6.German Cancer Research CenterHeidelbergGermany
  7. 7.Department of Human GeneticsThe University of ChicagoChicagoUSA
  8. 8.Department of MedicineThe University of ChicagoChicagoUSA
  9. 9.Cancer Research CenterThe University of ChicagoChicagoUSA

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