Breast Cancer Research and Treatment

, Volume 79, Issue 3, pp 355–364 | Cite as

HER2 Codon 655 Polymorphism and Risk of Breast Cancer in African Americans and Whites

  • Robert Millikan
  • Allison Eaton
  • Kendra Worley
  • Lorna Biscocho
  • Elizabeth Hodgson
  • Wen-Yi Huang
  • Joseph Geradts
  • Mary Iacocca
  • David Cowan
  • Kathleen Conway
  • Lynn Dressler
Article

Abstract

Background. Several recent epidemiologic studies examined the association between breast cancer risk and an inherited, single-nucleotide polymorphism in the HER2 gene, codon 655 G to A, which leads to an amino acid substitution of Ile to Val. Results of previous studies have been mixed, with most studies showing no association but some suggesting an association in younger women or women with a family history of breast cancer.

Methods. We conducted an association study of HER2 codon 655 genotype and breast cancer within the Carolina Breast Cancer study, a population-based, case-control study of in situ and invasive breast cancer in African American and white women in North Carolina. A total of 2015 cases and 1808 controls were genotyped.

Results. We observed no overall association between HER2 genotype and breast cancer. However, a modest positive association (OR = 2.3, 95% CI 1.0–5.3) was observed for Val/Val + Ile/Val versus Ile/Ile genotypes in women age 45 or younger with a family history of breast cancer. Val/Val homozygotes were more common among cases with in situ versus invasive disease (P = 0.002). Breast tumors from women with Val/Val genotype were more likely to exhibit HER2 overexpression, but the results were not statistically significant (P = 0.17).

Conclusions. The HER2 codon 655 polymorphism may be one of many low-penetrant genes that make a minor contribution to breast cancer, particularly in subgroups of women. Additional large studies, as well as data pooling, will be needed to estimate the contribution of such genes to breast cancer risk.

breast cancer HER2 polymorphism 

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References

  1. 1.
    Olayioye M, Neve R, Lane H, Hines N: The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19: 3159-3167, 2000Google Scholar
  2. 2.
    Porter-Jordan K, Lippman M: Overview of the biologic markers of breast cancer. Hematol Oncol Clin North Am 8: 73-100, 1994Google Scholar
  3. 3.
    Prenzel N, Rischer O, Streit S, Hart S, Ullrich A: The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocrine-Related Cancer 8: 11-31, 2001Google Scholar
  4. 4.
    Papewalis J, Nikitin A, Rajewsky M: G to A polymorphism at amino acid 655 of the human erbB-2/HER2 gene. Nucl Acids Res 19: 5452, 1991Google Scholar
  5. 5.
    Xie D, Shu X-O, Deng Z, Wen W-Q, Creek K, Dai Q, Gao Y-T, Jin F, Zheng W: Population-based case-control study of HER2 genetic polymorphisms and breast cancer risk. J Natl Cancer Inst 92: 412-417, 2000Google Scholar
  6. 6.
    Zheng W, Wen W-Q: Response [letter]. J Natl Cancer Inst 93: 1658-1659, 2001Google Scholar
  7. 7.
    Zheng W, Kataoka N, Xie D, Young S: Response [letter]. J Natl Cancer Inst 93: 558-559, 2001Google Scholar
  8. 8.
    Baxter S, Campbell I: Re: Population-based case-control study of HER2 genetic polymorphisms and breast cancer risk [letter]. J Natl Cancer Inst 93: 557-558, 2001Google Scholar
  9. 9.
    Wang-Gohrke S, Chang-Claude J: Re: Population-based case-control study of HER2 genetic polymorphisms and breast cancer risk [letter]. J Natl Cancer Inst 93: 1657-1658, 2001Google Scholar
  10. 10.
    Keshava C, McCanlies E, Keshava N, Wolff M, Weston A: Distribution of HER2 V655 genotypes in breast cancer cases and controls in the United States. Cancer Letters 173: 37-41, 2001Google Scholar
  11. 11.
    Newman B, Moorman P, Millikan R, Qaqish B, Geradts J, Aldrich T, Liu E: The Carolina Breast Cancer Study: integrating population-based epidemiology and molecular biology. Breast Cancer Research and Treatment 34: 51-60, 1995Google Scholar
  12. 12.
    Millikan R, Pittman G, Newman B, Rockhill B, Savitz D, Bell D: Cigarette smoking and N-acetyltransferases 1 and 2 and breast cancer. Cancer Epidem Biomark Prev 7: 371-378, 1998Google Scholar
  13. 13.
    Weinberg C, Sandler D: Randomized recruitment in casecontrol studies. Am J Epidem 134: 421-432, 1991Google Scholar
  14. 14.
    Dressler L, Geradts J, Burroughs M, Cowan D, Millikan R, Newman B: Policy guidelines for the utilization of formalin-fixed, paraffin-embedded tissue sections: The UNC SPORE experience. Breast Cancer Res Treat 58: 31-39, 1999Google Scholar
  15. 15.
    Furberg H, Millikan R, Dressler L, Newman B, Geradts J: Tumor characteristics in African American and white women. Breast Cancer Res Treatment 68: 33-43, 2001Google Scholar
  16. 16.
    Huang W-Y, Newman B, Millikan R, Conway K, Hulka B, Schell M, Liu E: Risk of breast cancer according to the status of HER2/neu oncogene amplification. Cancer Epidemiol Biomarkers Prev 9: 65-71, 2000Google Scholar
  17. 17.
    Dressler L, Cowan D, Huang W-Y, Tse J, Geradts J, Vick K, Conway K, Edmiston S, Little D, Newman B, Millikan B. Assessment of IHC and PCR to Determine HER2/neu status in 527 breast cancer specimens: the UNC SPORE Experience. Cancer Research. Proc AACR (Abstract), 2000Google Scholar
  18. 18.
    Schaid D, Jacobsen S: Biased tests of association: comparisons of allele frequencies when departing from Hardy-Weinberg equilibrium. Am J Epidem 149: 706-711, 1999Google Scholar
  19. 19.
    Rothman K, Greenland S: Modern Epidemiology. 2nd edn. Lippincott-Raven, Philadelphia, 1998Google Scholar
  20. 20.
    Ameyaw M-A, Thornton N, McLeod H: Re: Population-based case-control study of HER2 genetic polymorphisms and breast cancer risk [letter]. J Natl Cancer Inst 92: 1947, 2000Google Scholar
  21. 21.
    Pharoah P, Antoniou A, Bobrow M, Zimmern R, Easton D, Ponder B: Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31: 33-36, 2002Google Scholar
  22. 22.
    Liu E, Thor A, He M, Barcos M, Ljung B-M, Benz C: The HER2 (c-erbB-2) oncogene is frequently amplified in in situ carcinomas of the breast. Oncogene 7: 1027-1032, 1992Google Scholar
  23. 23.
    Allred D, Clark G, Molina R, Tandon A, Schnitt S, Gilchrist K, Osborne CK, Tormey D, McGuire W: Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol 23: 974-979, 1992Google Scholar
  24. 24.
    Millikan R, Pittman G, Duell E, Tse C-K, Moorman P, Newman B, Savitz D: Catechol-O-Methyltransferase (COMT) and breast cancer risk. Carcinogenesis 19: 1943-1947, 1998Google Scholar
  25. 25.
    Millikan R, Pittman G, Tse C-K, Savitz D, Newman B, Bell D: Glutathione-S-transferases M1, T1 and P1 and breast cancer. Cancer Epidem Biomark Prev 9: 567-573, 2000Google Scholar
  26. 26.
    Duell E, Millikan R, Pittman G, Winkel S, Lunn R, Tse C-K, Eaton A, Mohrenweiser H, Newman B, Bell D: Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidem Biomark Prev 10: 217-222, 2001Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Robert Millikan
    • 1
    • 2
  • Allison Eaton
    • 1
  • Kendra Worley
    • 1
  • Lorna Biscocho
    • 1
  • Elizabeth Hodgson
    • 1
  • Wen-Yi Huang
    • 1
  • Joseph Geradts
    • 3
  • Mary Iacocca
    • 3
  • David Cowan
    • 2
  • Kathleen Conway
    • 1
    • 2
  • Lynn Dressler
    • 2
  1. 1.Department of Epidemiology, School of Public Health, School of MedicineUniversity of North CarolinaChapel HillUSA
  2. 2.University of North CarolinaChapel HillUSA
  3. 3.Department of Pathology, Lineberger Comprehensive Cancer Center, School of MedicineUniversity of North CarolinaChapel HillUSA

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