The purpose of this paper is to assess the relationship between gene polymorphism in angiogenesis-related genes and radiation responses in nasopharyngeal carcinoma (NPC) patients. The genotypes of 180 NPC patients were analyzed by Sequenom MassARRAY. The response evaluation criteria in solid tumours were used for assessing efficacies, and the criteria of the Radiation Therapy Oncology Group or European Organization for Research & Treatment of Cancer were utilized for evaluating acute toxic reactions in response to radiation. Statistical methods included chi-square test, uni- and multivariate logistic regression analyses. Genotypic carriers of rs1800541 GT were at an elevated risk of developing grade 3+ oral mucositis, and a genetic variant of rs5333 was a predictor for a lower occurring risk of grade 2+ radiation-induced xerostomia. EDN1 rs1800541, rs2071942 and rs5370 variants were associated with a significantly higher risk of severe myelosuppression. SNPs in such angiogenesis-related genes as EDN1 rs1800541, rs2071942 & rs5370 and EDNRA rs5333 may serve as useful biomarkers for predicting the outcomes of NPC patients.

Abstract.Warfarin is an oral anticoagulant with significant interpatient variability in dosage. A large number of studies have confirmed that the individual warfarin dose is mainly affected by the cytochrome P450 complex subunit 2C9 and vitamin K epoxide reductase complex subunit 1. However, the association between cytochrome P450 4F2 (CYP4F2) gene polymorphisms and warfarin dosage in the Asian population remains controversial. To investigate the impact of the CYP4F2 polymorphism rs2108622 (p.V433M) on warfarin dose requirement, a systematic review and meta-analysis were conducted. According to the strict inclusion and exclusion criteria set, a comprehensive literature search was performed, and the studies published before August 5, 2015 were searched for in PubMed, EMBASE and the China National Knowledge Infrastructure databases. The references were checked by two independent reviewers. The association between the warfarin maintenance dose and CYP4F2 polymorphism was analyzed. Twenty-two studies were included in the meta-analysis. Compared with the CYP4F2 genotype CC, carriers of the CT and TT genotypes required a 9 [95% confidence interval (CI): 6.0-13.0] and 20% (95% CI, 13.0-27.0) higher warfarin dose, respectively. In the combined analysis, T carriers (CT+TT) required an 11% (95% CI, 8.0-14.0) higher warfarin dose compared to the CC genotype. In addition, there was a 10% (95% CI, 5.0-15.0) higher warfarin dose in TT carriers compared to the CT genotype (all P<0.05). The results of the meta-analysis suggest that the effects of the CYP4F2 polymorphism on individual warfarin dose have a statistically significant difference, and the effect degree is variable in the subgroups. Further studies are expected to explore whether the pharmacogenetics model including the CYP4F2 polymorphism can strengthen the prediction of warfarin dose. IntroductionWarfarin is a commonly oral anticoagulant, mainly used clinically in the treatment of thromboembolic diseases, such as atrial fibrillation (AF) and deep venous thrombosis (DVT); however, the existence of high interpatient variability in drug dosage may increase the risk of bleeding or thrombosis. Studies indicated that individual warfarin dose was influenced by a host of factors, including genetic and environmental factors. Genetic factors are one of the main reasons for the individual difference in warfarin maintenance dosage. Previous studies have also suggested that cytochrome P450 complex subunit 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphisms, age, weight and body surface area can explain ~50% of the influence on warfarin dose requirement (1-6). Therefore, there remains a 50% uncertainty of the other factors to be further explored.The cytochrome P450 4F2 (CYP4F2) gene, consisting of 13 exons and 12 introns and encoding 520 amino acid residues, is located on chromosome 19p13.12 in humans. Studies have shown that there are numerous single-nucleotide polymorphisms (SNPs) in the CYP4F2 gene open reading frame, such as rs2108622, rs2074...

There is considerable inter-individual variability in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiving the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system. The short-term effects of primary tumor and lymph node after radiotherapy were assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) of WHO. And acute radiation-induced toxic reactions were evaluated according to the Radiation Therapy Oncology Group or European Organization for Research and Treatment of Cancer (RTOG/EORTC). The effects of gene polymorphisms on clinical outcomes of chemoradiotherapy were assessed by chi-square test, univariate and multivariate logistic regression analyses. We found that CT and CT+CC genotypes of CANX rs7566 was significantly correlated with primary tumor treatment efficacy at 3 months after chemoradiotherapy and with occurrence of radiation-induced myelosuppression in Chinese NPC patients. CT and CT+CC genotypes of CALCR rs2528521 were significantly correlated with cervical lymph node efficacy at 3 months after chemoradiotherapy. And CC and CT+CC genotypes of VCP rs2074549 were significantly associated with occurrence of myelosuppression. In conclusion, SNPs of VCP rs2074549, CANX rs7566 and CALCR rs2528521 in ER stress pathway genes may serve as predictors for clinical outcomes of chemoradiotherapy in Chinese NPC patients.