汪丹 吴成凤 申文

[摘要] 目的 研究瞬時受体电位香草酸亚型1（TRPV1）基因多态性与肺癌中晚期癌痛患者阿片药物需要量的关联性。方法 选择2016年12月～2017年5月在徐州医科大学附属医院住院的肺癌中晚期（Ⅲ、Ⅳ期）患者191例（肺癌组）及健康体检者52名（健康对照组）。收集其外周静脉血标本，采用聚合酶链反应限制性酶切片段多态性（PCR-RFLP）方法对其进行TRPV1基因rs222747、rs8065080两个位点的基因型和等位基因分析，随机选择部分样品应用直接测序法验证其分型结果。采用视觉模拟量表评分法（VAS）对患者进行疼痛评估，应用吗啡当量比较不同基因型患者阿片药物的需要量。 结果 肺癌组和健康对照组TRPV1基因rs222747位点、rs8065080位点均可检出3种基因型：rs222747（CC、GC、GG），rs8065080（CC、TC、TT）。肺癌组与健康对照组rs222747位点的基因型和等位基因分布显示差异无统计学意义（P > 0.05），而肺癌组与健康对照组rs8065080位点的基因型和等位基因分布显示差异有统计学意义（P < 0.05）。肺癌组rs222747位点各基因型和等位基因患者的阿片药物日均需要量、体重标化日均需要量、体重表面积标化日均需要量差异均无统计学意义（P > 0.05）。 结论 尚不能认为TRPV1基因rs222747位点基因多态性与肺癌中晚期癌痛患者阿片药物需要量有关。

[关键词] 瞬时受体电位香草酸亚型1；基因多态性；肺癌；癌痛

[中图分类号] R730.5 [文献标识码] A [文章编号] 1673-7210（2018）09（a）-0087-04

[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.

[Key words] Transient receptor potential vanillic acid subtype 1； Gene polymorphism； Lung cancer； Cancer pain

在全球范围内，诸多癌症患者正饱受疼痛的煎熬。疼痛的影响因素有很多，包括生理、认知、情绪和基因等方面[1]。疼痛感知的个体差异在癌症病人中表现尤为突出[2]，其中基因因素是引起这种差异的重要原因[3]。目前，癌痛的药物治疗均采用WHO癌症疼痛三阶段治疗原则，但阿片类药物的长期使用会导致嗜睡、便秘、恶心呕吐、呼吸抑制、耐受性和成瘾性等副作用[4]。阿……