GSTP1 c.313A > G, XPD c.934G > A, XPF c.2505T > C and CASP9 c.-1339A > G Polymorphisms and Severity of Vomiting in Head and Neck Cancer Patients treated with Cisplatin Chemoradiation

作者：Carron Juliana; Lopes Aguiar Leisa; Dias Costa Ericka Francislaine; Silva Nogueira Guilherme Augusto; Penna Lima Tathiane Regine; Pincinato Eder Carvalho; Visacri Marilia Berlofa; Franca Quintanilha Julia Coelho; Moriel Patricia; Lourenco Gustavo Jacob; Passos Lima Carmen Silvia

来源：Basic and Clinical Pharmacology and Toxicology, 2017, 121(6): 520-525.

DOI：10.1111/bcpt.12842

<jats:title>Abstract</jats:title><jats:p>Cisplatin (<jats:styled-content style="fixed-case">CDDP</jats:styled-content>) chemotherapy associated with radiation (<jats:styled-content style="fixed-case">RT</jats:styled-content>) has been used in advanced head and neck squamous cell carcinoma (<jats:styled-content style="fixed-case">HNSCC</jats:styled-content>) patients, and vomiting is a common side effect during treatment. This prospective study aimed to identify the roles of <jats:italic><jats:styled-content style="fixed-case">GSTM</jats:styled-content>1</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">GSTT</jats:styled-content>1</jats:italic> (presents or nulls), <jats:italic><jats:styled-content style="fixed-case">GSTP</jats:styled-content>1</jats:italic> c.313A&gt;G, <jats:italic><jats:styled-content style="fixed-case">XPC</jats:styled-content></jats:italic> c.2815A&gt;C, <jats:italic><jats:styled-content style="fixed-case">XPD</jats:styled-content></jats:italic> c.934G&gt;A and c.2251A&gt;C, <jats:italic><jats:styled-content style="fixed-case">XPF</jats:styled-content></jats:italic> c.2505T&gt;C, <jats:italic><jats:styled-content style="fixed-case">ERCC</jats:styled-content>1</jats:italic> c.354C&gt;T, <jats:italic><jats:styled-content style="fixed-case">MLH</jats:styled-content>1</jats:italic> c.−93G&gt;A, <jats:italic><jats:styled-content style="fixed-case">MSH</jats:styled-content>2</jats:italic> c.211 + 9C&gt;G, <jats:italic><jats:styled-content style="fixed-case">MSH</jats:styled-content>3</jats:italic> c.3133G&gt;A, <jats:italic><jats:styled-content style="fixed-case">EXO</jats:styled-content>1</jats:italic> c.1765G&gt;A, <jats:italic><jats:styled-content style="fixed-case">TP</jats:styled-content>53</jats:italic> c.215G&gt;C, <jats:italic><jats:styled-content style="fixed-case">CASP</jats:styled-content>3</jats:italic> c.‐1191A&gt;G and c.‐1168G&gt;T, <jats:italic><jats:styled-content style="fixed-case">CASP</jats:styled-content>9</jats:italic> c.‐1339A&gt;G, <jats:italic><jats:styled-content style="fixed-case">CASP</jats:styled-content>8</jats:italic> c.‐937_‐932del<jats:styled-content style="fixed-case">AGTAAG</jats:styled-content>,<jats:italic> <jats:styled-content style="fixed-case">FAS</jats:styled-content></jats:italic> c.‐1378G&gt;A and c.‐671A&gt;G, and <jats:italic><jats:styled-content style="fixed-case">FASL</jats:styled-content></jats:italic> c.‐157‐687C&gt;T single nucleotide polymorphisms, involved in <jats:styled-content style="fixed-case">CDDP</jats:styled-content> metabolism, in vomiting severity in 88 <jats:styled-content style="fixed-case">HNSCC</jats:styled-content> patients treated with <jats:styled-content style="fixed-case">CDDP</jats:styled-content> and <jats:styled-content style="fixed-case">RT</jats:styled-content>. Ondansetron and dexamethasone were administered as anti‐emetic therapy. Patients with <jats:italic><jats:styled-content style="fixed-case">GSTP</jats:styled-content>1</jats:italic> c.313<jats:styled-content style="fixed-case">AG</jats:styled-content> or <jats:styled-content style="fixed-case">GG</jats:styled-content> genotype alone and combined with <jats:italic><jats:styled-content style="fixed-case">XPD</jats:styled-content></jats:italic> c.934<jats:styled-content style="fixed-case">GA</jats:styled-content> or <jats:styled-content style="fixed-case">AA</jats:styled-content>,<jats:italic> <jats:styled-content style="fixed-case">XPF</jats:styled-content></jats:italic> c.2505<jats:styled-content style="fixed-case">TC</jats:styled-content> or <jats:styled-content style="fixed-case">CC</jats:styled-content>, and <jats:italic><jats:styled-content style="fixed-case">CASP</jats:styled-content>9</jats:italic> c.‐1339<jats:styled-content style="fixed-case">AG</jats:styled-content> or <jats:styled-content style="fixed-case">GG</jats:styled-content> genotypes had 4.28, 5.00, 5.45 and 5.38 more chances of presenting moderate/severe vomiting than patients with others genotypes. Our data suggest, for the first time, that inherited abnormality in apoptosis pathway alone or combined with inherited abnormalities in <jats:styled-content style="fixed-case">DNA</jats:styled-content> repair pathway, is capable of modulating emesis in <jats:styled-content style="fixed-case">HNSCC</jats:styled-content> patients under <jats:styled-content style="fixed-case">CDDP</jats:styled-content> chemoradiation and may be used for selecting patients who should receive pre‐emptive anti‐emetic therapy.</jats:p>

• 出版日期2017-12