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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalBreast Cancer Research and Treatment
Volume85
Issue number2
DOIs
StatePublished - May 2004

Keywords

  • Breast cancer
  • COMT
  • CYP1B1
  • Estrogen-metabolism genes
  • Genetic epidemiology
  • Genetic polymorphism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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