Journal Article

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

William Chu, Anthony Fyles, Edward M. Sellers, David R. McCready, Joan Murphy, Tuya Pal and Steven A. Narod

in Carcinogenesis

Volume 28, issue 10, pages 2139-2142
Published in print October 2007 | ISSN: 0143-3334
Published online April 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm087
Association between CYP3A4 genotype and risk of endometrial cancer following tamoxifen use

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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 (CYP) 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 (OR = 1.6, 95% CI = 1.1–2.3, 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 ∼3-fold increase in the risk of developing endometrial cancer following tamoxifen treatment, compared with 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.

Journal Article.  3359 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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