title: Effects of SULT1A1 Copy Number Variation on Estrogen Concentration and Tamoxifen-Associated Adverse Drug Reactions in Premenopausal Thai Breast Cancer Patients: A Preliminary Study.
abstract: Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was 44.3±11.1 years, and they were subtyped as ER+/ progesterone receptor (PR) + (28 patients), ER+/ PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Science, Chulalongkorn University, Bangkok, Thailand E-mail : Nutthada.a@pharm.chula.ac.th.
authors.forename: Wanaporn
authors.initials: W
authors.lastname: Charoenchokthavee
authors.forename: Duangchit Panomvana Na
authors.initials: DP
authors.lastname: Ayudhya
authors.forename: Virote
authors.initials: V
authors.lastname: Sriuranpong
authors.forename: Nutthada
authors.initials: N
authors.lastname: Areepium
mesh_terms: D000293:Adolescent; D000328:Adult; D015239:Arylsulfotransferase / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000235:genetics*; D004965:Estrogen Antagonists / Q000009:adverse effects; D004967:Estrogens / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017697:Premenopause; D011379:Prognosis; D013629:Tamoxifen / Q000009:adverse effects*; D013785:Thailand; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human