Linc00312 Single Nucleotide Polymorphism as Biomarker for Chemoradiotherapy Induced Hematotoxicity in Nasopharyngeal Carcinoma Patients

Abstract

Background. Linc00312 is downregulated in nasopharyngeal carcinoma (NPC) and associates with poor treatment efficacy. Genetic variations are the main cause of individual differences in treatment response. The objective of this study is to explore the relationship between genetic variations of linc00312 and the risk of chemoradiotherapy induced toxic reactions in NPC patients. Methods. We used a bioinformatics approach to select 3 single nucleotide polymorphisms (SNPs) with regulatory feature in linc00312 (rs12497104, rs15734, and rs164966). 505 NPC patients receiving chemoradiotherapy with complete follow-up data were recruited. Genotyping was carried out by MassARRAY iPLEX platform. Univariate logistic and multivariate logistic regression were used to analyze the risk factors responsible for toxic reactions of NPC patients. Results. Our result demonstrated that linc00312 rs15734 ( G > A ) was significantly associated with severe leukopenia in NPC patients underwent chemoradiotherapy (AA vs. GG, OR = 3.145 , P = 0.029 ). In addition, the risk of severe leukopenia was remarkably increased to 5.635 times ( P = 0.034 ) in female with rs15734 AA genotype compared to male with rs15734 GG genotype. Moreover, patients with rs12497104 ( G > A ) AA genotype showed a 67.5% lower risk of thrombocytopenia than those with GG genotype ( P = 0.030 ). Remarkably, the younger patients ( age < 47 ) with rs12497104 AA genotype displayed a 90% decreased risk of thrombocytopenia compared with older patients ( age ≥ 47 ) carrying rs12497104 GG genotype ( P = 0.030 ). Conclusions. Genetic variations of linc00312 affect the risk of chemoradiotherapy induced hematotoxicity in nasopharyngeal carcinoma patients and may serve as biomarkers for personalized medicine.

LncRNA FAS-AS1 upregulated by its genetic variation rs6586163 promotes cell apoptosis in nasopharyngeal carcinoma through regulating mitochondria function and Fas splicing

“…Previous study has reported lncRNA GAS5 rs2067079 (C > T) could affect the secondary structure of GAS5 and was associated with an obviously increased risk of radio-chemotherapy induced hematotoxicities in NPC patients 36 . In addition, linc00312 rs12497104 (G > A) could destroy the binding between mir-411-3p and linc00312, and affect the expression of linc00312, thus conferring increased susceptibility risk and poorer overall survival in NPC patients 29 , 37 .…”

Impact of LINC00312 gene polymorphism coupled with habitual risks on buccal mucosa cancer

“…Two loci located within the LINC00312 gene (rs12497104 and rs164966) were chosen for analysis in this study on the basis of their putative association with nasopharyngeal carcinoma susceptibility 21 , 23 . The QIAamp DNA Blood Mini Kit (Qiagen) was used to extract genomic DNA from whole blood specimens.…”

“…Specifically, LINC00312 variants, rs15734 and rs164966, were associated with a decrease in the risks of developing NPC, as patients with rs12497104 polymorphisms showed a poorer overall survival [21,22]. In addition, association of rs12497104 and rs15734 with chemoradiotherapy-induced hematotoxicity in NPC was recently reported [23]. As LINC00312 was found to be implicated in the development of oral submucous fibrosis [24] and head and neck cancer [25], the impact of LINC00312 SNPs together with lifestyle-related risks on OSCC is in need of clarification.…”

Role of long non-coding RNA in chemoradiotherapy resistance of nasopharyngeal carcinoma

“…Linc00312 exhibits dysregulation and reduced expression in NPC, linked to its role in NPC progression, drug resistance, short-term efficacy, and OS ( 70 ). Upregulating Linc00312 enhances NPC sensitivity to radiotherapy by inhibiting radiation-induced signal transduction pathways and DNA damage repair–related protein expression ( 29 , 30 ). Aberrant expression of PTPRG-AS1, observed in various malignant tumors, including NPC, demonstrates its effect on radiosensitivity.…”