Ism that areReimer et al. BMC Cancer (2016) 16:Page 5 ofTable 3 SLCO1B
Ism that areReimer et al. BMC Cancer (2016) 16:Page 5 ofTable 3 SLCO1B1*5 genotype allele distribution as a function of resumption of menstrual bleeding (n = 50)SLCO1B1*5 (rs4149056) T/T (n = 26) C/T (n = 22) C/C (n = 2) Remained premenopausal CIA (n = 24) (n = 26) 8 (33.3 ) 14 (58.3 ) 2 (8.4 ) 18 (69.2 ) 8 (30.8 ) 0 P-value 0.Table 5 SLCO1B1*5 genotype allele distribution as a function of patient age group (n = 50)rs4149056 <35 years (n = 10) T/T C/T C/C 5 5 0 35?9 years 40?4 years >44 years (n = 13) (n = 20) (n = 7) 6 7 0 11 8 1 4 2 1 P-value 0.usually present in the liver or gastrointestinal tract. SNPs in drug transporters, metabolizing enzymes and drug targets have the potential to affect therapeutic efficacy and toxicity [26, 27]. Our study results are a further example of the importance of variant polymorphisms predicting toxicities from chemotherapy in breast cancer patients. Using a pharmacogenomic approach permitting rapid scan of multiple markers, a significant association with CIA in Causasian women was found only for the SLCO1B1*5 allele distribution (rs4149056) (Table 6). In particular, patients who have the homozygous (T/T) genotype of the rs4149056 polymorphism showed a higher risk for developing CIA compared with patients who have the homozygous (C/C) PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26795252 or heterozygous (C/T) genotype. In a genome-wide study the SEARCH Collaborative Group has identified the rs4149056 C allele in SLCO1B1 as being strongly associated with an increased risk of statin-induced myopathy [28]. No SNPs in any other region were clearly associated with myopathy. Several clinical studies in the past have investigated associations between rs4149056 SLCO1B1 genotypes and statin pharmacokinetics [22]. Although not all yielded significant results, the collective evidence indicates that statin blood concentrations are higher in people with the C allele [28]. Substrates for OATP1B1 include AZD-8055 web anticancer agents like methotrexate [29], gimatecan, SN-38 (the active metabolite of irinotecan), and pazopanib [23]. Certain SLCO1B1 variants associated with enhanced clearance of methotrexate increase the risk of gastrointestinal toxicity when this compound is used to treat children with acute lymphoblastic leukemia [30]. Endogenous substrates of SLCO1B1 include steroid hormone conjugates such as estradiol-17-glucuronideTable 4 SLCO1B1*5 genotype allele distribution as a function of chemotherapeutic regimen (n = 50)rs4149056 TAC FEC TC EC FAC AC P-value (n = 23) (n = 15) (n = 8) (n = 2) (n = 1) (n = 1) T/T C/T C/C 12 10 1 9 6 0 4 3 1 0 2 0 0 1 0 1 0 0 0.and estrone-3-sulfate [31]. In a nested case-control study in the California Teachers Study cohort, only genetic variation in SLCO1B1 was associated with breast cancer risk. There was also an indication that estrogenprogestin therapy (EPT) may interact with SNPs in SLCO1B1; one variant (rs4149013) was significantly associated with breast PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26240184 cancer risk in EPT users [32]. Furthermore, given the frequent occurrence of overlapping substrate specificities ?and the fact that functionally important coding-region SNPs in genes encoding members of some transporters families may not be common ?it might be most fruitful to focus on combinations of coding-region SNPs in genes encoding transporters that work in parallel or in series [33]. In our data (Additional file 4: Table S4), alongside the described significant SLCO1B1*5 polymorphism in relation to CIA, there was a trend for a second SLC transporter genotype (SLC15A2: rs2257.
