Breast Cancer Research and Treatment

, Volume 85, Issue 2, pp 121–131

A Family-based Genetic Association Study of Variants in Estrogen-metabolism Genes COMT and CYP1B1 and Breast Cancer Risk

  • Habibul Ahsan
  • Yu Chen
  • Alice S. Whittemore
  • Muhammad G. Kibriya
  • Irina Gurvich
  • Ruby T. Senie
  • Regina M. Santella
Article

DOI: 10.1023/B:BREA.0000025401.60794.68

Cite this article as:
Ahsan, H., Chen, Y., Whittemore, A.S. et al. Breast Cancer Res Treat (2004) 85: 121. doi:10.1023/B:BREA.0000025401.60794.68

Abstract

In this paper, we report findings from a family-based association study examining the association between polymorphisms in two key estrogen-metabolism genes CYP1B1 (codon 432 G → C and codon 453 A → G variants) and COMT (codon 158 G → A variant) and female breast cancer. We conducted the study among 280 nuclear families containing one or more daughters with breast cancer with a total of 1124 family members (702 with available constitutional DNA and questionnaire data and 421 without). These nuclear families were selected from breast cancer families participating in the Metropolitan New York Registry (MNYR) — one of the six centers of NCI's Breast Cooperative Family Registry. We used likelihood-based statistical methods to examine the allelic associations. We found none of the variant alleles of the CYP1B1 and COMT genes to be associated with breast cancer in these families. This was consistent with results from matched case-control analyses using all available sib-ships in these families. However, we found that parental carrier status of the CYP1B1 codon 453 variant G allele and the COMT codon 158 variant A allele was associated with breast cancer risk in daughters (independent of the daughters' own genotype). In conclusion, findings from this family-based study indicate that a woman's own CYP1B1 or COMT genotypes are not associated with her breast cancer risk. Although the study found that parental carrier status of certain CYP1B1 or COMT genotypes might be associated with daughter's breast cancer risk, the biological basis as well as independent confirmation of this finding need to be investigated in future larger family-based studies before making meaningful inferences.

breast cancer COMT CYP1B1 estrogen-metabolism genes genetic epidemiology genetic polymorphism 

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Habibul Ahsan
    • 1
    • 3
  • Yu Chen
    • 1
  • Alice S. Whittemore
    • 4
  • Muhammad G. Kibriya
    • 1
  • Irina Gurvich
    • 2
  • Ruby T. Senie
    • 1
    • 3
  • Regina M. Santella
    • 2
    • 3
  1. 1.Department of EpidemiologyMailman School of Public HealthNew YorkUSA
  2. 2.Department of Environmental Health SciencesMailman School of Public HealthNew YorkUSA
  3. 3.Herbert Irving Comprehensive Cancer CenterColumbia UniversityNew YorkUSA
  4. 4.Department of Health Research and Policy, Division of EpidemiologyStanford UniversityStanfordUSA