摘要
背景与目的:有研究表明p21cip1和p27kip1的基因多态性与乳腺癌、肺癌、前列腺癌等肿瘤易感性有关。本研究分析中国北方高发区人群食管鳞状细胞癌(ESCC)和贲门腺癌(GCA)与p21cip1和p27kip1基因多态性之间的关系。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299例ESCC患者、256例GCA患者及437名健康对照人群p21cip13′非翻译区和p27kip1第109位密码子基因多态性分布情况。结果:ESCC患者组p21cip1T等位基因型频率(42.8%)显著高于健康对照组(36.7%)(P=0.02),ESCC和GCA患者组p27kip1V等位基因型频率(分别为96.8%和96.1%)均显著高于健康对照组(92.9%)(P值分别为0.00和0.02)。ESCC患者组p21cip1基因型频率分布与健康对照组相比有显著性差异(P=0.04),与C/C和C/T基因型相比,T/T基因型可显著增加ESCC的发病风险(校正OR=1.93,95%CI=1.12～3.94)。ESCC和GCA患者组p27kip1基因型频率分布与健康对照组相比均有显著性差异(P分别为0.00和0.01),与V/G和G/G基因型相比,V/V基因型可显著增加ESCC和GCA的发病风险(校正OR分别为2.44和2.01,95%CI分别为1.21～4.02和1.12～3.68)。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V/G和G/G基因型相比,V/V基因型可显著增加吸烟人群患ESCC和GCA(校正OR分别为2.24和2.61,95%CI分别为1.14～4.03和1.25～3.82)以及有家族史人群患ESCC的发病风险(校正OR=2.04,95%CI=1.04～3.43)。两基因联合分析显示,携带p21cip1T/T和p27kip1V/V基因型可显著增加患食管癌和贲门癌的发病风险(校正OR分别为3.78和2.56,95%CI分别为1.46～5.89和1.06～4.78)。结论:在中国北方人群中,p21cip1基因多态性可能与食管癌的易感性有关,p27kip1基因多态性可能与食管癌和贲门癌的易感性有关,而且这两个基因的多态性可能在食管癌和贲门癌发病中起联合作用。
BACKGROUND ＆ OBJECTIVE. Researches showed that polymorphisms of p21^cip1 and p27^kip1 genes have associations with susceptibilities of breast cancer, lung cancer, prostate cancer, and so on. This study was to investigate the possible association of functional polymorphisms of p21^cip1 and p27%kip1 genes with susceptibilities of esophageal squamous cell carcinoma （ESCC） and gastric cardiac adenocarcinoma （GCA） in a population from a high incidence region in north China. METHODS. The single nucleotide polymorphisms （SNPs） in the 3＇- untranslated region of p21^cip1 gene and in codon 109 of p27^kip1 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） in 299 ESCC patients, 256 GCA patients, and 437 healthy controls from a high incidence region of north China. RESULTS. The frequency of p21^cip1 T altelotype was significantly higher in ESCC patients than in healthy controls （42.8% vs. 36.7%, P=0.02）. The frequency of p27^kip1 V allelotype was significantly higher in ESCC and GCA patients than in healthy controls （96.8% and 96.1% vs. 92.9%, P=0.001, P=0.02）. The distribution of p21^cip1 genotypes among ESCC patients was significantly different from that among healthy controls （P=0.04）; compared with the combination of the C/C and C/T genotypes, the T/T genotype significantly elavated the risk of developing ESCC Eadjusted odds ratio （OR）=1.93, 95% confidence interval （CI）=1.12-3.94]. The distribution of p27^kip1 genotypes among ESCC and GCA patients were significantly different from that among healthy controls （P=0.002, P=0.01）; compared with the combination of V/G and G/G genotypes, the V/V genotype significantly elavated the risk of developing ESCC and GCA （adjusted OR =2.44, 95% CI =1.21-4.02; adjusted OR=2.01, 95% CI=1.12-3.68）. When stratified for smoking and family history of upper gastrointestinal cancers （UGIC）, compared with the combination of V/G and G/G genetypes, the V/V genotype significantly elavated the risk of developing both ESCC and GCA in smokers （adjusted OR=2.24, 95% C1=1.14-4.03; adjusted OR=2.61, 95% CI=1.25-3.82） and ESCC in individuals with positive family history of UGIC （adjusted OR =2.04, 95% CI =1.04-3.43）. The combination of p21^cip1 T/T and p27^kip1 V/V genotypes significantly elavated the risk of developing ESCC and GCA （adjusted OR=3.78, 95% C1=1.46-5.89; adjusted OR=2.56, 95% CI=1.06- 4.78）. CONCLUSION： In north China, p21^cip1 polymorphisms might be correlated with the susceptibility of ESCC, p27^kip1 polymorphisms might be correlated with the susceptibilities of ESCC and GCA, and they might have synergetic effect on ESCC and GCA development.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2006年第2期194-199,共6页
Chinese Journal of Cancer
基金
国家自然科学基金项目(No.30371591)~~
