Linc00312 Single Nucleotide Polymorphism as Biomarker for Chemoradiotherapy Induced Hematotoxicity in Nasopharyngeal Carcinoma Patients
Zhen Guo, Ya-Jing Wang, Binsheng He, Ji Zhou
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 ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>G</a:mi> <a:mo>></a:mo> <a:mi>A</a:mi> </a:math> ) was significantly associated with severe leukopenia in NPC patients underwent chemoradiotherapy (AA vs. GG, <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mtext>OR</c:mtext> <c:mo>=</c:mo> <c:mn>3.145</c:mn> </c:math> , <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo>=</e:mo> <e:mn>0.029</e:mn> </e:math> ). In addition, the risk of severe leukopenia was remarkably increased to 5.635 times ( <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo>=</g:mo> <g:mn>0.034</g:mn> </g:math> ) in female with rs15734 AA genotype compared to male with rs15734 GG genotype. Moreover, patients with rs12497104 ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>G</i:mi> <i:mo>></i:mo> <i:mi>A</i:mi> </i:math> ) AA genotype showed a 67.5% lower risk of thrombocytopenia than those with GG genotype ( <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>P</k:mi> <k:mo>=</k:mo> <k:mn>0.030</k:mn> </k:math> ). Remarkably, the younger patients ( <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mtext>age</m:mtext> <m:mo><</m:mo> <m:mn>47</m:mn> </m:math> ) with rs12497104 AA genotype displayed a 90% decreased risk of thrombocytopenia compared with older patients ( <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mtext>age</o:mtext> <o:mo>≥</o:mo> <o:mn>47</o:mn> </o:math> ) carrying rs12497104 GG genotype ( <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>P</q:mi> <q:mo>=</q:mo> <q:mn>0.030</q:mn> </q:math> ). Conclusions. Genetic variations of linc00312 affect the risk of chemoradiotherapy induced hematotoxicity in nasopharyngeal carcinoma patients and may serve as biomarkers for personalized medicine.