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Variants in estrogen-biosynthesis genes CYP17 and CYP19 and breast cancer risk: a family-based genetic association study

Habibul Ahsan12*, Alice S Whittemore3, Yu Chen1, Ruby T Senie12, Steven P Hamilton4, Qiao Wang2, Irina Gurvich2 and Regina M Santella25

Author Affiliations

1 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA

2 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York, USA

3 Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA

4 Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York USA

5 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA

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Breast Cancer Res 2005, 7:R71-R81  doi:10.1186/bcr951

Published: 11 November 2004



Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first family-based association study examining associations between female breast cancer risk and polymorphisms in two key estrogen-biosynthesis genes CYP17 (T→C promoter polymorphism) and CYP19 (TTTA repeat polymorphism).


We conducted the study among 278 nuclear families containing one or more daughters with breast cancer, with a total of 1123 family members (702 with available constitutional DNA and questionnaire data and 421 without them). These nuclear families were selected from breast cancer families participating in the Metropolitan New York Registry, one of the six centers of the National Cancer Institute's Breast Cancer Family Registry. We used likelihood-based statistical methods to examine allelic associations.


We found the CYP19 allele with 11 TTTA repeats to be associated with breast cancer risk in these families. We also found that maternal (but not paternal) carrier status of CYP19 alleles with 11 repeats tended to be associated with breast cancer risk in daughters (independently of the daughters' own genotype), suggesting a possible in utero effect of CYP19. We found no association of a woman's breast cancer risk either with her own or with her mother's CYP17 genotype.


This family-based study indicates that a woman's personal and maternal carrier status of CYP19 11 TTTA repeat allele might be related to increased breast cancer risk. However, because this is the first study to report an association between CYP19 11 TTTA repeat allele and breast cancer, and because multiple comparisons have been made, the associations should be interpreted with caution and need confirmation in future family-based studies.

breast cancer; cyp17; cyp19; estrogen biosynthesis genes; family-based design