P21基因多态性与华北食管癌的相关性

Association of P21 gene polymorphisms with esophageal squamous cell carcinoma in North China

目的:探讨P21基因外显子的3非翻译区(UTR)第20碱基对的单核苷酸多态性对食管鳞状细胞癌(ESCC)发生及淋巴结转移的影响.方法:选择202例ESCC患者和265例健康对照个体,采集静脉抗凝血5mL,同时收集病史、个人及肿瘤家族史.以蛋白酶K消化-饱和氯化钠盐析法提取外周血白细胞DNA,分别采用PCR-片断长度分析和PCR-限制性片段长度多态性(RFLP)方法检测P21外显子的3UTR第20碱基对单核苷酸多态性基因型.结果:ESCC患者的P21基因3UTR的多态性基因型和等位基因型分布与健康对照组差异无统计学意义(P>0.05).ESCC吸烟组患者P21的T/T基因型频率(26.0%)显著高于健康吸烟组(12.0%,χ2=8.60,P=0.014).与C/C基因型相比,携带T/T基因型可增加吸烟者的ESCC发病风险(经性别和年龄校正的OR值为3.36,95%CI=1.45-7.75).而在非吸烟的患者和健康个体中,P21的基因型及等位基因型频率均差异无统计学意义(P>0.05).有淋巴结转移组的P21的T/T基因型频率(26.4%)高于无淋巴结转移组(15.3%,χ2=6.128,P=0.013).与常见基因型C/C相比,携带T/T基因型可增加ESCC患者淋巴结转移的风险,经性别、年龄校正的OR值分别为3.11(95%CI=1.28-7.52).结论:P213UTR的T/T基因型可能增加中国北方吸烟人群ESCC易感性并可能增加ESCC患者淋巴结转移的风险性.

AIM： To explore the influence of the single nucleo- tide polymorphism variants （SNPs） in the 3＇-untranslated region （3＇UTR） of P21 gene on the development and lymphatic metastases of esophageal squamous cell carcinoma （ESCC）. METHODS： The hospital-based case-control study included 202 ESCC patients and 265 healthy controls. Genomie DNA was extracted by using proteinase K digestion followed by a salting-out procedure. The SNPs of P21 were analyzed by polymerase chain reaction （PCR）-fragment length analysis and PCR-restrietion fragment length polymorphism analysis （ PCR-RFLP ）. RESULTS： The overall genotype and allelotype distributions of P21 3＇ UTR polymorphisms in ESCC patients were not significantly different from those in healthy controls （ P 〉 0.05 ）. Stratification analysis revealed that the P21 gene Tr allele frequency in smoking patients （26.0%） was significantly higher than that in healthy smokers （ 12.0% , x^2 = 8.60, P = 0.014）. Therefore, compared with P21 C/C genotype, smokers with the T/T genotype significantly had a higher risk to develop ESCC （ sex and age adjusted A = 3.36, 95% CI = 1.45 - 7.75）. However, P21 allele was not significantly different in both non-smoking ESCC group and healthy group （ P 〉 0.05 ）. The ESCC cases were further stratified according to the status of lymphatic metastasis at the time of diagnosis and the results showed that the p21 T/T allele （26.4%）was more common in ESCC patients with lymphatic metastasis than those without lymphatic metastasis （ 15.3%, x^2 = 6. 128, P = 0.013）. Compared with familiar monadelphous the C/C genotype, T/T genotype significantly increased the risk of lymphatic metastasis （ sex and age adjusted A = 3. 11, 95% CI = 1.28 - 7.52）. CONCLUSION： The P21 T/T allele may increase the susceptibility to ESCC among smokers in North China and the risk of lymphatic metastasis in ESCC.