Association of TRPV1 gene polymorphism with opioid requirements in patients with advanced lung cancer
WANG Dan1 WU Chengfeng1 SHEN Wen2▲
1.Department of Anesthesiology, Graduate School of Xuzhou Medical University, Jiangsu Province, Xuzhou 221004, China;
2.Department of Pain, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, Xuzhou 221004, China
Abstract:Objective To investigate the relationship between transient receptor potential vanilloid 1 (TRPV1) gene polymorphisms and opioid requirements in patients with advanced lung cancer. Methods Peripheral venous blood samples were collected from 191 patients with advanced lung cancer (stages Ⅲ and Ⅳ) (lung cancer group) and 52 healthy controls (healthy control group) in Affiliated Hospital of Xuzhou Medical University from December 2016 to May 2017. The genotypes of rs222747 and rs8065080 of TRPV1 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Part of samples were randomly selected and verified by direct sequencing method. Visual analogue scale (VAS) was used to evaluate the pain of patients and morphine equivalents were used to compare the requirements of opioids for patients with different genotypes. Results Three genotypes were detected in lung cancer group and healthy control group: rs222747 (CC, GC, GG) and rs8065080 (CC, TC, TT). There was no significant difference in the genotype and allele distribution of rs222747 between the lung cancer group and healthy control group (P > 0.05). The distribution of genotypes and alleles of the rs8065080 between the lung cancer group and the healthy control group were statistically significant(P < 0.05). There was no significant difference in the 24 h-opioids doses, weight-adjusted-24 h-opioids doses, weight-surface area-adjusted-24 h-opioids doses between the genotypes and alleles of rs222747 in the lung cancer group with pain(P > 0.05). Conclusion There is insufficient evidence that the rs222747 polymorphisms of TRPV1 are associated with the requirement of opioids in advanced lung cancer patients with pain.
[1] Andersen S,Skorpen F. Variation in the COMT gene:implications for pain perception and pain treatment [J]. Pharmacogenomics,2009,10(4):669-684.
[2] Yao P,Ding YY,Wang ZB,et al. Effect of gene polymorphism of COMT and OPRM1 on the preoperative pain sensitivity in patients with cancer [J]. Int J Clin Exp Med,2015, 8(6):10036-10039.
[3] Wang XS,Song HB,Chen S,et al. Association of single nucleotide polymorphisms of ABCB1,OPRM1 and COMT with pain perception in cancer patients [J]. J Huazhong Univ Sci Technolog Med Sci,2015,35(5):752-758.
[4] 余婷.对癌性疼痛的止痛的思考[J].基础医学,2016,3(6):247-248.
[5] 朱敏,潘志强,张璐,等.ABCB1基因多态性与癌痛感知及癌痛病人阿片需求量的关联性分析[J].中国疼痛学杂志,2017,23(6):426-433.
[6] Dai Y. TRPs and pain [J]. Semin Immunopathol,2016,38(3):277-291.
[7] 张小宁,杨娟.Etiology of nonspecific chronic cough in children and relationship between TRPV1 gene polymorphisms and nonspecific chronic cough [J].中国当代儿科杂志,2012, 14(7):524-528.
[8] 支修益,吴一龙.原发性肺癌诊疗规范(2011年版)[J].中国肺癌杂志,2011,15(12):677-688.
[9] 赵英.疼痛的测量和评估方法[J].中国临床康复,2002,6(16):2347-2352.
[10] Gong XD,Wang JY,Liu F,et al. Gene polymorphisms of OPRM1 A118G and ABCB1 C3435T may influence opioid requirements in Chinese patients with cancer pain [J].Asian Pac J Cancer Prev,2013,14(5):2937-2943.
[11] Woolf CJ,Ma Q. Nociceptors-noxious stimulus detectors [J]. Neuron,2007,55(3):353-364.
[12] Volkers L,Mechioukhi Y,Coste B. Piezo channels:from structure to function [J]. Pflugers Arch,2015,467(1):95-99.
[13] Waxman SG,Merkies ISJ,Gerrits MM,et al. Sodium channel genes in pain-related disorders:phenotype–genotype associations and recommendations for clinical use [J]. Lancet Neurol,2014,13(11):1152-1160.
[14] Christoph T,Grunweller A,Mika J,et al. Silencing of vanilloid receptor TRPV1 by RNAi reduces neuropathic and visceral pain in vivo [J]. Biochem Biophys Res Commun,2006,350(1):238-243.
[15] Wei SY,Chen LF,Lin MW,et al. The OPRM1 A118G polymorphism modulates the descending pain modulatory system for individual pain experience in young women with primary dysmenorrheal [J]. Sci Rep,2017,7:39906.
[16] Hoffmeyer S. Functional polymorphisms of the human multidrug-resistance gene:Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo [J]. Proc Natl Acad Sci USA,2000, 97(7):3473-3478.
[17] Khalil H,Sereika SM,Dai F,et al. OPRM1 and COMT Gene-Gene Interaction Is Associated With Postoperative Pain and Opioid Consumption After Orthopedic Trauma [J]. Biol Res Nurs,2017,19(2):170-179.
[18] Solovieva S,Leino A,Saarela J,et al. Possible association of interleukin 1 gene locus polymorphisms with low back pain [J]. Pain,2004,109(1):8-19.
[19] Chen SR,Pan HL. Removing TRPV1-expressing primary afferent neurons potentiates the spinal analgesic effect of δ-opioid agonists on mechano-nociception [J]. Neuropharmacology,2008,55(2):215-222.
[20] Rathee PK,Distler C,Obreja O. PKA/AKAP/VR-1 Module:A Common Link of Gs-Mediated Signaling to Thermal Hyperalgesia [J]. J Neurosci,2002,22(11):4740-4745.