Family-based genetic association study of insulin-like growth factor I microsatellite markers and premenopausal breast cancer risk

  • Gordon Fehringer
  • Norman F. Boyd
  • Julia A. Knight
  • Andrew D. Paterson
  • Gillian S. Dite
  • Graham G. Giles
  • Melissa C. Southey
  • Irene L. Andrulis
  • John L. Hopper
  • Hilmi Ozcelik
Epidemiology

Abstract

Several studies suggest that higher circulating insulin-like growth factor I (IGF-I) levels are associated with premenopausal breast cancer risk. Breast cancer risk and circulating IGF-I concentration appear to be partly heritable, thus genetic variation at IGF1 could influence IGF-I levels and breast cancer risk. We investigated the association of IGF1 CA repeat variants with premenopausal breast cancer risk using a family-based design. The study sample included 840 families from the Ontario Familial Breast Cancer Registry (OFBCR) and the Australian Breast Cancer Family Registry (ABCFR). Three CA repeat variants, at 5′, 3′, and in intron 2 were genotyped (5′CA, 3′CA, In2CA). We found several nominally significant associations. The 5′CA-21 allele (P = 0.03) and In2CA-212 allele (P = 0.04) were associated with lower risk, and the In2CA-216 allele with higher risk (P = 0.04) for the combined ABCFR–OFBCR. These associations were not significant after taking into account multiple comparisons. In2CA-216 was more strongly associated with risk when we used a recessive instead of an additive model (P = 0.01). 5′CA alleles of repeat length 18–20 were associated with higher risk (P = 0.02), and 5′CA alleles of >20 repeats were associated with lower risk (P = 0.01). These associations were significant in the OFBCR (In2CA-216 recessive, P = 0.02; 5′CA 18–20 and >20 allele grouping, P = 0.01) but not strongly supported by the ABCFR (In2CA-216 recessive, P = 0.14; 5′CA 18–20, P = 0.25; 5′CA >20, P = 0.20). The associations we found could be due to chance as many comparisons were made. Our results do not strongly support an association between these IGF1 variants and breast cancer risk.

Keywords

Breast cancer Insulin-like growth factor I–IGF1 Polymorphism Microsatellite 

Notes

Acknowledgments

We thank Hamdi Jarjanazi and Keith Wong for their contributions to this study. This work was supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry and P·I.s [including P·I.s from Cancer Care Ontario (U01 CA69467) and University of Melbourne (U01 CA69638)]. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CFR.

Supplementary material

10549_2009_336_MOESM1_ESM.doc (213 kb)
(DOC 213 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Gordon Fehringer
    • 1
    • 2
  • Norman F. Boyd
    • 3
  • Julia A. Knight
    • 1
    • 4
  • Andrew D. Paterson
    • 1
    • 5
  • Gillian S. Dite
    • 6
  • Graham G. Giles
    • 6
    • 7
  • Melissa C. Southey
    • 8
  • Irene L. Andrulis
    • 9
    • 10
    • 11
    • 12
    • 13
  • John L. Hopper
    • 6
  • Hilmi Ozcelik
    • 9
    • 10
    • 11
  1. 1.Dalla Lana School of Public HealthUniversity of TorontoTorontoCanada
  2. 2.Population Studies and SurveillanceCancer Care OntarioTorontoCanada
  3. 3.Campbell Family Institute for Breast Cancer ResearchOntario Cancer InstituteTorontoCanada
  4. 4.Prosserman Centre for Health Research, Samuel Lunenfeld Research InstituteMount Sinai HospitalTorontoCanada
  5. 5.Program in Genetics and Genome BiologyThe Hospital for Sick ChildrenTorontoCanada
  6. 6.Centre for Molecular, Environmental, Genetic and Analytic EpidemiologyThe University of MelbourneCarltonAustralia
  7. 7.Cancer Epidemiology CentreThe Cancer Council VictoriaMelbourneAustralia
  8. 8.Department of PathologyThe University of MelbourneMelbourneAustralia
  9. 9.Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research InstituteMount Sinai HospitalTorontoCanada
  10. 10.Department of Pathology and Laboratory MedicineMount Sinai HospitalTorontoCanada
  11. 11.Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  12. 12.Department of Molecular GeneticsUniversity of TorontoTorontoCanada
  13. 13.Cancer Care OntarioTorontoCanada

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