Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines

• Published in: Scientific reports 2014-07, Vol.4 (1), p.5697, Article 5697
• Main Authors: Huang, Liu, Chen, Fengju, Chen, Yangyang, Yang, Xiaomei, Xu, Sanpeng, Ge, Shuwang, Fu, Shengling, Chao, Tengfei, Yu, Qianqian, Liao, Xin, Hu, Guangyuan, Zhang, Peng, Yuan, Xianglin
• Format: Article
• Language: English
• Subjects: 45/22; 45/23; 692/308/575; 692/53/2422; 692/699/67/1504/2330; 82/51; Adolescent; Adult; Aged; Alleles; Antimetabolites, Antineoplastic - therapeutic use; Cancer; Chemotherapy; Disease-Free Survival; Female; Fluorouracil - therapeutic use; Gastrointestinal Neoplasms - blood; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - mortality; Gene Frequency; Genes; Genetic Association Studies; Humanities and Social Sciences; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; multidisciplinary; Phosphorylase; Platelet Count; Platelet-derived endothelial cell growth factor; Polymorphism, Single Nucleotide; Proportional Hazards Models; Science; Single-nucleotide polymorphism; Survival; Thrombocytosis; Thrombopoietin; Thymidine; Thymidine phosphorylase; Thymidine Phosphorylase - genetics; Treatment Outcome; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep05697

The predictive value of thymidine phosphorylase gene variants (TP, also called platelet-derived endothelial cell growth factor) and thrombocytosis were controversial and worthy of further study in gastrointestinal cancer (GIC) patients. We screened all of the common missense single nucleotide polymorphisms (MAF ≥ 0.1) in fluoropyrimidines (FU) pathway genes (including TP , TS , ENOSF1 and DPD ). Three of them were selected and genotyped using Sequenom MassARRAY in 141 GIC patients. TP expression was assessed by immunohistochemistry. Our aim was to evaluate the prognostic significance of studied genes and platelet counts in GIC patients. Multivariate analyses indicated in rs11479-T allele carriers, platelet counts negatively correlated to overall survival. In addition, T allele of TP : rs11479 was associated with higher TP expression in cancer tissues. We suggest TP : rs11479 variant combined with platelet counts may be useful prognostic makers in GIC patients receiving first-line FU chemotherapy and thrombopoietin factor should be used with caution in the rs11479 T allele bearing patients.