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Germline polymorphisms may have a significant effect on the pharmacokinetics of the purchase soma cheapest Baltimore drug and pharmacodynamics.6 EGFR, which encodes purchase soma cheapest Baltimore a direct target of erlotinib is polymorphic.7, 8 A polymorphism in intron is microsatellitesassociésthe expression of EGFR, with the repeat length of the cytosine-adenosine (CA) nucleótidosinversamente correlated with EGFR mRNA and protein, and sensitivity to erlotinib in vitro.9-12 There are differences marked ethnic intronic locus.

7 More recent studies have identified single nucleotide polymorphisms (SNPs) in the 5 'regulatory EGFR. Two-216g / T (rs712829) and-191C / A (rs712830) are in the essential purchase soma cheapest Baltimore promoter region of EGFR. The variant-216g / T was associated with increased activity purchase soma cheapest Baltimore and EGFR promoter gene expression mediated by an altered interaction with SP1, while the 191C / A is close to a major transcription initiation sites.8 recently - 216g / T were reported to be associated with gefitinib response and toxicity in lung cancer patients.13 A nonsynonymous SNP at codon 497 of EGFR (purchase soma cheapest Baltimore rs11543848), a G to a disturbance, resulting in the substitution amino Arg (R) Lys (K) .14 Only the missense polymorphism of EGFR common reported to date, and the K allele appears to decrease the activity of these polymorphisms EGFR.15 if they are involved in the mechanism underlying side effects and response to tyrosine kinase inhibitors (CCI) in patients with cancer is not yet understood. Previous studies of purchase soma cheapest Baltimore EGFR inhibitors have found an association between plasma concentrations of the drug at steady state and the severity of the rash and diarrhea.16, 17 Variation of genes involved in the pharmacokinetics of TKI may contribute to these reaction conditions. Erlotinib is a substrate for CYP3A4 and CYP3A5.purchase soma cheapest Baltimore 18 These two genes are highly polymorphic and expressed.19, 20 polymorphisms in the CYP3A5 gene may lead to important interindividual and interracial differences in CYP3A-dependent drug purchase soma cheapest Baltimore metabolism.21, 22 CYP3A5 * 3 is purchase soma cheapest Baltimore a common AG transition in intron 3 purchase soma cheapest Baltimore of CYP3A5 (rs776746), which creates a cryptic splice site and leads to a truncated protein production.21 CYP3A5 G / G homozygotes lack of CYP3A5 expression, whereas individuals with at least one wild type allele (A / A or A express / G) A common transition CYP3A5.21 AG 5 'regulation of CYP3A4 (CYP3A4 * 1B, rs2740574) was associated with purchase soma cheapest Baltimore prostate cancer and risk23-25 ​​may increase moderately CYP3A4 activity, 26 a substantial effect of this SNP in the hepatic expression of CYP3A4 has not been demonstrated.27-30 These polymorphisms are known if linked.31 purchase soma cheapest Baltimore haplotypes these two SNPs affect the metabolism of erlotinib and the influence of interindividual variability in the toxicity of erlotinib. In addition to drug metabolizing enzymes, drug transporters may also be involved in the purchase soma cheapest Baltimore pharmacokinetics of erlotinib. Recent studies indicate that gefitinib and erlotinib are substrates ABCG2.32-35 Two nonsynonymous SNPs ABCG2, CA 421 (Q141K, rs2231142) and 34GA (V12M, rs2231137) is purchase soma cheapest Baltimore common.36 141K-39 polymorphism was associated with lower expression and activity of ABCG2 and greater accumulation of gefitinib and two purchase soma cheapest Baltimore erlotinib.35, 36.40 A recent clinical study demonstrated an association between 141K and diarrhea in patients treated with gefitinib.41 recently we identified four functional polymorphisms in the 5 'regulatory ABCG2 (Poonkuzhali et al, manuscript submitted for publication). The promoter 15994GA (rs7699188) NPSN (predicted gain because purchase soma cheapest Baltimore of a HNF4 site) was significantly associated with increased ABCG2 expression in many purchase soma cheapest Baltimore tissues. 15622CT carriers of the expression (novel) NPSN ABCG2 showed reduced in many tissues. A 16702GA intron 1SNP (rs2046134) was associated with a strong expression in the liver and is expected as a result deGATA4 win a seat. Finally, 1143CT (rs2622604) was associated with low expression in the purchase soma cheapest Baltimore intestine. If these polymorphisms on the pharmacokinetics of erlotinib and other TKI has not been reported.

Nosotrosla hypothesized that germline polymorphisms in EGFR and other candidate genes influence the toxicity of erlotinib. We conducted a prospective study of 80 patients with lung cancer, head and neck cancer purchase soma cheapest Baltimore and ovarian cancer receiving standard dose (150 mg daily) erlotinib to assess the impact of genetic polymorphisms included in the rash and diarrhea The two main side effects.