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Carcinogenesis Advance Access published online on April 13, 2007
Carcinogenesis, doi:10.1093/carcin/bgm087
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Association between CYP3A4 genotype and risk of endometrial cancer following tamoxifen use

William Chu1, Anthony Fyles1, Edward Sellers2,3, David McCready4, Joan Murphy5, Tuya Pal6 and Steven A. Narod7

1 Department of Radiation Oncology, Princess Margaret Hospital-University Health Network, Toronto, Ontario, Canada
2 Department of Medicine, Pharmacology and Psychiatry, University of Toronto, Toronto, Ontario, Canada
3 Ventana Clinical Research Corporation, Toronto, Ontario, Canada
4 Department of Surgical Oncology, Princess Margaret Hospital- University Health Network, Toronto, Ontario, Canada
5 Department of Gynaecologic Oncology, Princess Margaret Hospital- University Health Network, Toronto, Ontario, Canada
6 Department of Interdisciplinary Oncology, University of South Florida, H. Lee Moffitt Cancer Centre and Research Institute, Tampa, Florida
7 Centre for Research in Women's Health, Women's College Hospital, Toronto, Ontario, Canada

Address for correspondence: Dr. S.A. Narod, 790 Bay Street, Room 750a, Toronto, Ontario, Canada, M5G 1N8, Telephone: (416) 351-3765, Fax: (416) 351-3767, E-mail: steven.narod{at}wchospital.ca

Tamoxifen is a selective estrogen receptor modulator that is used to treat and to prevent breast cancer; however, its use is associated with an increased risk of endometrial cancer. Tamoxifen is metabolized by various cytochrome P450 enzymes, but predominantly by CYP3A4. In this study, we examined whether a genetic variant of the CYP3A4 gene, CYP3A4*1B, influences endometrial cancer risk - alone and when associated with tamoxifen exposure. We conducted a case-control study on 566 endometrial cancer cases and 964 ethnically-matched controls. The variant CYP3A4 allele was present in 6% of the controls and 9% of the endometrial cancer patients (O.R.=1.6, 95% CI=1.1 to 2.3; p = 0.02). The allele was more common in women with endometrial cancer who had been treated with tamoxifen for breast cancer (16%). Women who carried the CYP3A4*1B allele had approximately a 3-fold increase in the risk of developing endometrial cancer following tamoxifen treatment, compared to women who did not take tamoxifen (p = 0.004). These findings suggest that a subgroup of breast cancer patients who carry the CYP3A4*1B allele and take tamoxifen may be at increased risk of developing endometrial cancer.

Received August 15, 2006; revised March 29, 2007; accepted April 2, 2007.


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