Effects of SLCO1B1 Polymorphisms on Plasma Estrogen Concentrations in Women with Breast Cancer Receiving Aromatase Inhibitors Exemestane and Letrozole

Abstract

Aim: This study tested for associations between SLCO1B1 polymorphisms and circulating estrogen levels in women with breast cancer treated with letrozole or exemestane. Patients & methods: Postmenopausal women with hormone-receptor positive breast cancer were genotyped for SLCO1B1*5 (rs4149056) and rs10841753. Pretreatment and on-treatment plasma estrogens and aromatase inhibitor (AI) concentrations were measured. Regression analyses were performed to test for pharmacogenetic associations with estrogens and drug concentrations. Results: SLCO1B1*5 was associated with elevated pretreatment estrone sulfate and an increased risk of detectable estrone concentrations after 3 months of AI treatment. Conclusion: These findings suggest SLCO1B1 polymorphisms may have an effect on estrogenic response to AI treatment, and therefore may adversely impact the anticancer effectiveness of these agents.

Association between SLCO1B1 genetic polymorphisms and bleeding risk in patients treated with edoxaban

“…Rs4149056 ( SLCO1B1 *5) is a functional polymorphism in exon 5 and a well-studied SNP associated with drug toxicities such as stain-induced myopathy and methotrexate toxicity 13 , 14 . Rs4149056 was typically associated with reduced transporter activity, resulting in increased systemic drug exposure and increased toxicity risk 13 , 38 . In our study, rs4149056 significantly increased the bleeding risk.…”

“…Tag SNPs of the SLCO1B1 gene were assigned with a condition MAF ≥ 20% and an r 2 threshold of 0.8 in Asian populations. Second, among them, nine SNPs, including one synonymous SNP (rs4149057 29 , 30 ) and eight intronic SNPs (rs11045879 31 , 32 , rs12317268 33 , 34 , rs4149081 31 , 35 , rs999278 36 , rs2306283 13 , 37 , rs10841753 14 , 38 , rs2417957 39 , 40 , and rs4149042 41 ) of SLCO1B1 were selected based on previous studies and PharmGKB 42 , which is a pharmacogenomics Knowledge Base that offers information about how human genetic variation impacts drug response. Although rs4149056 (missense SNP) had a MAF of 0.13, it was included because it has been investigated for various drug-induced toxicity and studied with edoxaban 10 , 11 , 13 , 14 , 32 , 38 .…”

Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma

“…ABCB8 mediates doxorubicin resistance by protecting the mitochondrial genome in melanoma (34). SLCO1B1 polymorphisms influence the estrogenic response to aromatase inhibitor treatment in breast cancer (35). PPARG activates lipid signaling pathways, and high levels of PPARG/ FASN confer a poor prognosis in prostate cancer (36).…”