title: Effects of gene polymorphisms in the endoplasmic reticulum stress pathway on clinical outcomes of chemoradiotherapy in Chinese patients with nasopharyngeal carcinoma.
abstract: There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing 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.
authors.affiliation: Inner Mongolia Autonomous Region People's Hospital, Hohhot 010017, China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Guo
authors.affiliation: Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Wan-le
authors.initials: WL
authors.lastname: Ma
authors.affiliation: Jiangxi Province Tumor Hospital, Nanchang 330029, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Liu
authors.affiliation: Jiangxi Province Tumor Hospital, Nanchang 330029, China.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Jiangxi Province Tumor Hospital, Nanchang 330029, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Medical Experiments, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Peng
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.affiliation: Jiangxi Province Tumor Hospital, Nanchang 330029, China.
authors.forename: Jin-Gao
authors.initials: JG
authors.lastname: Li
authors.affiliation: Department of Oncology, Fourth Affiliated Hospital, Guangxi Medical University, Liuzhou 545005, China.
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Yang
authors.affiliation: Affiliated Hunan Provincial Tumor Hospital, Xiangya Medical School, Central South University, Changsha 410013, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Cheng-Xian
authors.initials: CX
authors.lastname: Guo
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D044466:Asian People; D037281:Calnexin / Q000235:genetics; D002277:Carcinoma / Q000378:metabolism / Q000628:therapy*; D018797:Cell Cycle Proteins / Q000235:genetics; D059248:Chemoradiotherapy; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000628:therapy*; D011110:Polymorphism, Genetic; D018003:Receptors, Calcitonin / Q000235:genetics; D015398:Signal Transduction; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D018003:Receptors, Calcitonin; D037281:Calnexin; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein