【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。更多还原

【Abstract】 BACKGROUND & OBJECTIVE: Researches showed that polymorphisms of p21cip1 and p27kip1 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 p21cip1 and p27kip1 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 p21cip1 gene and in codon 109 of p27kip1 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 p21cip1 T allelotype was significantly higher in ESCC patients than in healthy controls (42.8% vs. 36.7%, P=0.02). The frequency of p27kip1 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 p21cip1 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 [adjusted odds ratio (OR) =1.93, 95% confidence interval (CI) =1.12- 3.94]. The distribution of p27kip1 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% CI=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 p21cip1 T/T and p27kip1 V/V genotypes significantly elavated the risk of developing ESCC and GCA (adjusted OR=3.78, 95% CI=1.46- 5.89; adjusted OR=2.56, 95% CI=1.06- 4.78). CONCLUSION: In north China, p21cip1 polymorphisms might be correlated with the susceptibility of ESCC, p27kip1 polymorphisms might be correlated with the susceptibilities of ESCC and GCA, and they might have synergetic effect on ESCC and GCA development.更多还原