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Polymorphisms in steroid hormone pathway genes and mammographic density
Christopher A Haiman1, Susan E Hankinson, Immaculata De Vivo
1Department of Epidemiology, Harvard School of Public Health Boston, MA, USA.
Breast Cancer Research and Treatment
|February 27, 2003
Summary
Genetic variations in steroid hormone genes influence mammographic density differently based on menopausal status. Certain UGT1A1 and AIB1 genotypes are linked to breast density changes, particularly in postmenopausal women using hormone therapy.
Area of Science:
- Genetics
- Endocrinology
- Oncology
Background:
- Mammographic density is a significant risk factor for breast cancer.
- Breast density is influenced by steroid hormone pathways.
- Genetic polymorphisms in hormone-related genes may affect breast density variations.
Purpose of the Study:
- To investigate the association between polymorphisms in eight candidate genes involved in steroid hormone pathways and mammographic breast density.
- To examine if these associations differ by menopausal status and postmenopausal hormone (PMH) use.
Main Methods:
- Cross-sectional analysis of 538 participants from the Nurses' Health Study.
- Assessment of mammographic breast density using a computer-assisted technique.
- Genotyping for 10 polymorphisms in genes including CYP17, CYP19, CYP1A1, CYP1B1, COMT, UGT1A1, AR, and AIB1.
Main Results:
- No consistent associations were found for CYP17, CYP19, CYP1B1, COMT, CYP1A1, or AR polymorphisms with breast density.
- Premenopausal women with the UGT1A1 7/7 genotype had lower breast density.
- Postmenopausal women with the UGT1A1 7/7 genotype had higher breast density, especially current PMH users.
- Postmenopausal women with shorter AIB1 alleles also showed increased breast density.
Conclusions:
- Most evaluated gene variants are not strong predictors of breast density.
- UGT1A1 and AIB1 genotypes show differential associations with breast density based on menopausal status.
- Further research is needed to corroborate findings related to UGT1A1 and AIB1 in relation to menopausal status and breast density.