摘要
目的：研究中国北方高发区人群食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）与肿瘤坏死因子（tumor necrosis factor，TNF）基因多态性的关系。方法：应用聚合酶链反应限制性片段长度多态性（PCR-RFLP）方法检测291例ESCC患者及437名正常对照的TNF-α-308G／A和TNF-β＋252G／A多态性分布情况。结果：正常对照组的TNF-α1／1，1／2和2／2的基因型频率分别为89．4％，9．2％和1．4％，TNF-βB1／B1，B1／B2和B2／B2的基因型频率分别为12．6％，32．3％和55．1％。ESCC患者组与正常对照组间的TNF-α-308G／A和TNF-β＋252G／A等位基因型及基因型分布均无统计学差异。当按吸烟和上消化道肿瘤家族史状况进行分层分析时发现，与TNF-βB2／B2基因型相比，TNF-βB1／B1和B1／B2基因型均能显著增加家族史阴性人群患食管癌的发病风险（校正OR值分别为2．01和1．89，95％CI分别为1．02～4．49和1．10～2．65）。单体型分析显示，与TNF-α1／TNF-βB2相比，TNF-α／TNF-βB1可增强ESCC的发病风险（OR=1.30，95％CI=1．03～1．65）。2个多态性位点联合分析显示，与TNF-α和TNF-βB2／B2基因型相比，TNF-α1／2或TNF-α2／2及TNF-βB1／B2基因型可显著降低食管癌的发病风险。（OR=0．37，95％CI=0．15～0．92）。结论：TNF-α-308G／A和TNF-β＋252G／A基因多态性可能与ESCC的易感性无关，但是这2个位点的基因多态性可能对ESCC的发病起联合作用。
Objective： To investigate the possible association of the functional polymorphisms in the tumor necrosis factor （TNF） genes with susceptibility to esophageal squamous cell carcinoma （ESCC） in a population from a high incidence region in North China. Methods：The single nucleotide polymorphisms （SNP） of TNFα-308G/A and TNFβ＋ 252G/A were genotyped by polymerase chain reaction restriction fragment length polymorphism （PCR RFLP） analysis in 291 ESCC patients and 437 healthy controls from a high incidence region in North China. Results： Among healthy controls, frequencies of the TNFα 1/1,1/2 and 2/2 genotypes were 89. 4%, 9. 2%, and 1.4%, those of the TNFβ B1/B1, B1/B2 and B2/B2 genotypes were 12. 6%, 32. 3%, and 55.1 %, respectively, No significant difference was found in the overall genotype and allelotype distribution of the TNFα-308G/A and TNFβ＋ 252G/A SNPs between cancer patients and controls. When stratified for family history of upper gastrointestinal cancers（UGIC）, both of the B1/B1 and B1/B2 genotype significantly increased the risk of ESCC in individuals with negative family history of UGIC, compared with the B2/B2 genotype （the age and gender adjusted OR=2.01 and 1, 89.95% CI=1. 02-4.49 and 1.10-2.65,respectively）. Haplotype analysis showed that against TNFα1/TNFβB2, TNFα1/TNFβB1 can significantly enhanced the risk of ESCC（OR= 1.30,95%CI= 1.03-1.65）. When the two TNF polymorphisms were combined to analyze, individuals with the TNFβ B1/B2 and TNFα1/2 or 2/2 genotypes significantly reduced the risk of ESCC, compared with those harboring the TNFβ B2/B2 and TNFα 1/1 genotypes （OR = 0.37,95% CI= 0.15-0.92）. Conclusion：The TNFα-308G/A and TNF β ＋252G/A polymorphisms might not be correlated with the susceptibility to ESCC in North China, but they might have combined effect on ESCC development .
出处
《肿瘤》
CAS
CSCD
北大核心
2006年第3期254-258,共5页
Tumor
基金
国家自然科学基金资助项目(编号:30371591)
关键词
肿瘤坏死因子
单核苷酸多态性
食管鳞状细胞癌
易感性
Tumor necrosis factor t Single nucleotide polymorphism
Esophageal squamous cell carcinoma
Susceptibility
