Association between CYP3A4 genotype and risk of endometrial cancer following tamoxifen use.
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 approximately 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.
Chu
William
W
Department of Radiation Oncology, Princess Margaret Hospital-University Health Network, Toronto, Ontario, Canada.
Fyles
Anthony
A
Sellers
Edward M
EM
McCready
David R
DR
Murphy
Joan
J
Pal
Tuya
T
Narod
Steven A
SA
D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D009864:Ontario; D017698:Postmenopause; D017697:Premenopause; D012042:Registries; D012189:Retrospective Studies; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects; D013629:Tamoxifen / Q000009:adverse effects*
D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human