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 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.

The impacts of genetic polymorphisms in genes of base excision repair pathway on the efficacy and acute toxicities of (chemo)radiotherapy in patients with nasopharyngeal carcinoma

“…Acute radiation toxicity was evaluated from the first day to the end of radiotherapy. In our study, radiation-induced mucositis and dermatitis were evaluated and scored according to RTOG/EORTC acute radiation morbidity score criteria [ 34 , 35 ]. Patients with high grade of toxicity were compared with patients with low toxicity.…”

“…The efficacy at the end of radiotherapy and at 3 months after radiotherapy was evaluated by RECIST 1.1 [ 34 , 36 ] based on MRI imaging and nasopharyngoscope. The RECIST 1.1 defines the efficacy with complete remission (CR), partial remission (PR), stable disease (SD) and progression disease (PD).…”

Current Status and Future Perspectives about Molecular Biomarkers of Nasopharyngeal Carcinoma

“…For example, Yu et al (2016) reported gene polymorphisms in Wnt/βcatenin including catenin β-1 gene rs1880481, rs3864004, glycogen synthase kinase-3β (GSK-3β) gene rs3755557 and adenomatous polyposis coli (APC) gene rs454886 were associated with poor responses to RT [122]. Other gene polymorphisms, such as X-ray repair crosscomplementing 1 (XRCC1) rs25489, calcitonin receptor rs2528521, XRCC1 Codon399, and valosin-containing protein rs2074549, which can predict therapeutic outcomes and toxic side effects, were also investigated [123][124][125][126]. Besides that, certain polymorphisms were found to be susceptible to metastasis.…”

Research status and prospects of biomarkers for nasopharyngeal carcinoma in the era of high‑throughput omics (Review)

“…Yu et al ( 53 ) analyzed 9 potential functional SNPs in four genes in the Wnt/β-catenin pathway and found that patients carrying catenin β-1 rs1880481, rs3864004; glycogen synthase kinase-3β rs3755557; or adenomatous polyposis coli rs454886, may have a poor prognosis and can develop radiation-induced dermatitis and oral mucositis. Furthermore, several studies have discussed the potential of SNPs of different genes, such as X-ray repair cross-complementing 1 ( XRCC1 ) rs25489, XRCC1 Codon399, valosin-containing protein rs2074549 and rcalcitonin receptor rs2528521 in the base excision repair pathway and the endoplasmic reticulum stress pathway to predict the therapeutic effect and toxic reactions in NPC ( 54 - 57 ). However, it is worth noting that the cases involved in these studies included a number of patients with stages III-IVa NPC.…”