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目的:探讨转化生长因子β受体Ⅰ型(transforming growth factor-beta receptor type 1 gene,TGFBR1)Int7G24A和*6A单核苷酸多态性(single nucleotide polymorphisms,SNPs)与中国北方人群贲门腺癌(gastric cardia adenocarcinoma,GCA)遗传易感性的关系。方法:分别采用PCR-RFLP和PCR的方法检测468例GCA患者和584例健康对照人群中TGFBR1基因第7内含子Int7G24A和第1外显子*6ASNPs分布情况,同时对110例GCA患者术后切除肿瘤组织采用免疫组织化学方法检测TGFBR1蛋白的表达情况,并与其基因型进行相关性分析。结果:TGFBR1基因Int7G24A SNPs位点的基因型和等位基因型频率在GCA组和对照组间的分布差异有统计学意义(P<0.05),A等位基因携带者患GCA的风险是G等位基因的1.34倍[经性别、年龄和上消化管肿瘤家族史校正后的比值比(odds ratio,OR)=1.34,95%可信区间(confidence interval,CI)=1.03～1.87],与GG基因型相比,携带AA基因型可显著增加GCA的发病风险(校正后的OR=2.17,95%CI=1.15～3.72)。当按肿瘤分期进行分层分析时发现,与GG基因型相比,携带GA和AA基因型可显著增加Ⅲ期和Ⅳ期GCA的发病风险(校正后的OR=1.41,95%CI=1.05～1.98)。TGFBR1基因*6ASNPs位点的基因型及等位基因型频率在GCA患者组和对照组之间,其分布差异均无统计学意义(P>0.05)。GCA组织中TGFBR1蛋白的阳性表达率为27.3%,显著低于癌旁正常组织的100%(P<0.01),TGFBR1蛋白在GCA中的表达与TGFBR1基因Int7G24A和*6A位点的基因型之间无明显相关性(P>0.05)。结论:TGFBR1基因Int7G24A位点A等位基因可能是我国北方人群GCA的遗传易感基因,携带A等位基因的个体可增加GCA的发病风险。
Objective: To investigate the relationship between single nucleotide polymorphisms (SNPs) of transforming growth factor-beta receptor type 1 gene (TGFBR1), Int7G24A and * 6A and gastric cardia adenocarcinoma gastric cardia adenocarcinoma, GCA) genetic predisposition. Methods: The distribution of Int7G24A and exon 1 6ASNPs of TGFBR1 gene in 468 patients with GCA and 584 healthy controls were detected by PCR-RFLP and PCR respectively. At the same time, 110 patients with GCA The tumor tissue was excised and the expression of TGFBR1 protein was detected by immunohistochemistry. The correlation analysis was carried out with the genotypes. Results: The frequencies of genotypes and alleles of TGFβ1 in Int7G24A gene of TGFBR1 gene were significantly different between GCA group and control group (P <0.05), and the risk of GCA in A allele was G Odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.03-1.87), which was 1.34 times higher than that of GG Compared with genotypes, AA genotype could significantly increase the risk of GCA (adjusted OR = 2.17, 95% CI = 1.15-3.72). When stratified by tumor stage, it was found that carrying GA and AA genotypes significantly increased the risk of stage III and IV GCA compared with GG genotype (adjusted OR = 1.41, 95% CI = 1.05 ~ 1.98). The genotype and allele frequencies of * 6ASNPs in TGFBR1 gene were not significantly different between GCA patients and controls (P> 0.05). The positive expression rate of TGFBR1 protein in GCA tissues was 27.3%, which was significantly lower than that in adjacent normal tissues (P <0.01). The expression of TGFBR1 protein in GCA and the genotypes of TGFBR1 gene Int7G24A and * 6A No significant correlation (P> 0.05). CONCLUSION: The A allele of TGFBR1 gene at site of Int7G24A may be a genetic predisposition to GCA in northern China. Individuals with A allele may increase the risk of GCA.