乙醇脱氢酶1B-rs1229984位点基因单核苷酸多态性与食管癌患者临床特征及预后的关系
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摘要
目的探讨乙醇脱氢酶1B(alcohol dehydrogenase 1B, ADH1B)-rs1229984位点基因单核苷酸多态性(single nucleotide polymorphism, SNP)对食管癌患者临床病理特征及预后的影响。方法 132例食管癌患者为食管癌组,108例体检健康者为对照组,采集2组外周静脉血提取血液基因组DNA,采用二对引物-PCR法检测ADH1B-rs1229984基因SNP;比较2组ADH1B-rs1229984基因型和等位基因频率,分析ADH1B-rs1229984基因型与患者临床病理特征的关系;比较不同基因型食管癌患者的生存期;采用Cox比例风险回归模型分析影响食管癌患者预后的危险因素。结果 ADH1B在rs1229984存在SNP,分别为野生型纯合子GG型、突变杂合子AG型、突变纯合子AA型;2组ADH1B-rs1229984位点基因型分布频率比较差异有统计学意义(P<0.05),食管癌组G等位基因频率(51.52%)明显高于对照组(42.13%)(P<0.05);GG+AG基因型食管癌患者TNM分期Ⅲ期(89.47%)、低分化(93.48%)、浸润程度T_4期(93.33%)和淋巴结转移(88.89%)比率高于AA基因型(10.53%、6.52%、6.67%、11.11%)(P<0.05),年龄、性别比例、肿瘤直径、肿瘤部位与AA基因型比较差异均无统计学意义(P>0.05);AG+GG基因型食管癌患者中位生存期[(17.31±2.89)个月]短于AA基因型[(26.75±4.45)个月](P<0.05),1、2、3 a生存率(61.86%、19.59%、9.28%)低于AA基因型(97.14%、74.29%、37.14%)(P<0.05);淋巴结转移与ADH1B-rs1229984 GG基因型为影响食管癌患者预后的危险因素(OR=1.852,95%CI:1.339～2.561,P=0.026;OR=2.171,95%CI:1.675～2.815,P=0.013)。结论ADH1B-rs1229984基因SNP与食管癌患者临床病理特征有关,且该基因位点GG基因型预示患者预后不良。
Objective To investigate the relationships of single nucleotide polymorphism(SNP) of alcohol dehydrogenase 1 B(ADH1 B)-rs1229984 locus with the clinicopathological features and prognosis in patients with esophageal cancer. Methods The genomic DNA was extracted from the peripheral venous blood in 132 patients with esophageal cancer(esophageal cancer group) and 108 healthy volunteers(control group). The polymorphism of ADH1 B-rs1229984 gene was detected by PCR with confronting two-pair primers. The ADH1 B-rs1229984 genotype and allele frequency were compared between two groups. The relationship between ADH1 B-rs1229984 genotype and clinicopathological characteristics was analyzed. The survival time was compared in patients with different genotypes, and Cox proportional hazards model was used to analyze the risk factors for the prognosis of esophageal cancer. Results The SNP of ADH1 B was found in rs1229984, in wild homozygote GG type, mutant heterozygote AG type and mutant homozygote AA type. The frequency distribution of ADH1 B-rs1229984 genotype differed between two groups(P<0.05),and the G allele frequency was significantly higher in esophageal cancer group(51.52%)than that in control group(42.13%)(P<0.05).The proportions of TNM stageⅢ(89.47%),poorly differentiated(93.48%),invasive stage T4(93.33%)and lymph node metastasis(88.89%)of GG+AG genotype were significantly higher than those of AA genotype(10.53%,6.52%,6.67%,11.11%)in esophageal cancer group(P<0.05),and the age,sex ratio,diameter and location of tumors showed no significant difference compared with those of AA genotype(P>0.05).The median survival time was significantly shorter in AG+GG genotype esophageal cancer patients((17.31±2.89)months)than that in AA genotype patients((26.75±4.45)months)(P<0.05),and the 1-,2-and 3-year survival rates(61.86%,19.59%,9.28%)were significantly lower than those of AA genotype patients(97.14%,74.29%,37.14%)(P<0.05).Lymph node metastasis and ADH1 B-rs1229984 GG genotype were the risk factors for the prognosis of esophageal cancer(OR=1.852,95%CI:1.339-2.561,P=0.026;OR=2.171;95%CI:1.675-2.815,P=0.013).Conclusion The SNP of ADH1 B-rs1229984 is associated with the clinicopathological features of esophageal cancer,and the GG genotype predicts apoor prognosis.
Objective To investigate the relationships of single nucleotide polymorphism(SNP) of alcohol dehydrogenase 1 B(ADH1 B)-rs1229984 locus with the clinicopathological features and prognosis in patients with esophageal cancer. Methods The genomic DNA was extracted from the peripheral venous blood in 132 patients with esophageal cancer(esophageal cancer group) and 108 healthy volunteers(control group). The polymorphism of ADH1 B-rs1229984 gene was detected by PCR with confronting two-pair primers. The ADH1 B-rs1229984 genotype and allele frequency were compared between two groups. The relationship between ADH1 B-rs1229984 genotype and clinicopathological characteristics was analyzed. The survival time was compared in patients with different genotypes, and Cox proportional hazards model was used to analyze the risk factors for the prognosis of esophageal cancer. Results The SNP of ADH1 B was found in rs1229984, in wild homozygote GG type, mutant heterozygote AG type and mutant homozygote AA type. The frequency distribution of ADH1 B-rs1229984 genotype differed between two groups(P<0.05),and the G allele frequency was significantly higher in esophageal cancer group(51.52%)than that in control group(42.13%)(P<0.05).The proportions of TNM stageⅢ(89.47%),poorly differentiated(93.48%),invasive stage T4(93.33%)and lymph node metastasis(88.89%)of GG+AG genotype were significantly higher than those of AA genotype(10.53%,6.52%,6.67%,11.11%)in esophageal cancer group(P<0.05),and the age,sex ratio,diameter and location of tumors showed no significant difference compared with those of AA genotype(P>0.05).The median survival time was significantly shorter in AG+GG genotype esophageal cancer patients((17.31±2.89)months)than that in AA genotype patients((26.75±4.45)months)(P<0.05),and the 1-,2-and 3-year survival rates(61.86%,19.59%,9.28%)were significantly lower than those of AA genotype patients(97.14%,74.29%,37.14%)(P<0.05).Lymph node metastasis and ADH1 B-rs1229984 GG genotype were the risk factors for the prognosis of esophageal cancer(OR=1.852,95%CI:1.339-2.561,P=0.026;OR=2.171;95%CI:1.675-2.815,P=0.013).Conclusion The SNP of ADH1 B-rs1229984 is associated with the clinicopathological features of esophageal cancer,and the GG genotype predicts apoor prognosis.
引文
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[12] 黄建新,李馨,王瑜,等.多个单核苷酸多态性位点与食管癌和胃癌患病风险的相关性分析[J].重庆医学,2018,47(14):1889-1895.
[13] 周荣秒,李琰,王娜,等.PD-1基因多态性与食管癌遗传易感性关联的研究[J].肿瘤,2017,37(1):89-95.
[14] 杜淑娇,胡晓雯,蒋婕,等.ADH1B基因启动子区多态性和结直肠癌易感性关联分析[J].中国科学:生命科学,2017,47(4):369-376.
[15] AOKI Y,WEHAGE S L,TALALAY P.Quantification of skin erythema response to topical alcohol in alcohol-intolerant East Asians[J].Skin Res Technol,2017,23(4):593-596.
[16] LI D,ZHANG R,JIN T,et al.ADH1B and CDH1 polymorphisms predict prognosis in male patients with non-metastatic laryngeal cancer[J].Oncotarget,2016,7(45):73216-73228.
[17] GUO E,WEI H,LIAO X,et al.Prognostic value of alcohol dehydrogenase mRNA expression in gastric cancer[J].Oncol Lett,2018,15(4):5505-5516.
[18] AVINCSAL M O,SHINOMIYA H,TESHIMA M,et al.Impact of alcohol dehydrogenase-aldehyde dehydrogenase polymorphism on clinical outcome in patients with hypopharyngeal cancer[J].Head Neck,2018,40(4):770-777.
[2] 孔敏,陈保富,王春国,等.术前放化疗合并腔镜手术近期疗效敏感的食管癌患者不同预后结局原因分析[J].中华全科医学,2017,15(10):1669-1671,1734.
[3] 张耀勇,宋志雨.选择性动脉灌注化疗联合三维适形放疗治疗中晚期食管癌探讨[J].医药论坛杂志,2014,35(1):100-102.
[4] PIEROG J,BIELEWICZ M,WOJCIK J,et al.Evaluation of the metabolic response to open and minimally invasive resection of the oesophagus due to oesophageal cancer[J].Kardiochir Torakochirurgia Pol,2018,15(3):151-156.
[5] 裴忠玲,郭卿,孙新臣,等.血管内皮生长因子VEGF单核苷酸多态性与同步放化疗后食管鳞癌患者预后关系的研究[J].四川医学,2015,36(6):779-782.
[6] 沈霜婷,郑喆文,廖正凯.18F-FDG PET/CT对食管癌新辅助放化疗后组织病理学反应预测的研究进展[J].中华实用诊断与治疗杂志,2019,33(2):187-190.
[7] HE L,DENG T,LUO H.Aldehyde dehydrogenase 2 (ALDH2) polymorphism and the risk of alcoholic liver cirrhosis among east Asians:a meta-analysis[J].Yonsei Med J,2016,57(4):879-884.
[8] 施贵冬,罗志林,付茂勇,等.国际抗癌联盟-美国癌症联合委员会第7版食管癌和胃癌TNM分期系统在预测食管胃交界腺癌Siewert Ⅱ型患者预后中的价值[J].中华肿瘤杂志,2014,36(12):916-921.
[9] 徐寅生,韩羽凤,黄玲玲.食管癌淋巴结转移的CT诊断标准与病理对照研究[J].吉林医学,2013,34(3):522-523.
[10] SAITO T,TOYA R,YOSHIDA N,et al.Spleen dose-volume parameters as a predictor of treatment-related lymphopenia during definitive chemoradiotherapy for esophageal cancer[J].In Vivo,2018,32(6):1519-1525.
[11] VIRGILIO E,CECI D,CAVALLINI M.Surgical endoscopic vacuum-assisted closure therapy (EVAC) in treating anastomotic leakages after major resective surgery of esophageal and gastric cancer[J].Anticancer Res,2018,38(10):5581-5587.
[12] 黄建新,李馨,王瑜,等.多个单核苷酸多态性位点与食管癌和胃癌患病风险的相关性分析[J].重庆医学,2018,47(14):1889-1895.
[13] 周荣秒,李琰,王娜,等.PD-1基因多态性与食管癌遗传易感性关联的研究[J].肿瘤,2017,37(1):89-95.
[14] 杜淑娇,胡晓雯,蒋婕,等.ADH1B基因启动子区多态性和结直肠癌易感性关联分析[J].中国科学:生命科学,2017,47(4):369-376.
[15] AOKI Y,WEHAGE S L,TALALAY P.Quantification of skin erythema response to topical alcohol in alcohol-intolerant East Asians[J].Skin Res Technol,2017,23(4):593-596.
[16] LI D,ZHANG R,JIN T,et al.ADH1B and CDH1 polymorphisms predict prognosis in male patients with non-metastatic laryngeal cancer[J].Oncotarget,2016,7(45):73216-73228.
[17] GUO E,WEI H,LIAO X,et al.Prognostic value of alcohol dehydrogenase mRNA expression in gastric cancer[J].Oncol Lett,2018,15(4):5505-5516.
[18] AVINCSAL M O,SHINOMIYA H,TESHIMA M,et al.Impact of alcohol dehydrogenase-aldehyde dehydrogenase polymorphism on clinical outcome in patients with hypopharyngeal cancer[J].Head Neck,2018,40(4):770-777.