DNMT3A/3B基因启动子区SNPs与宿迁地区胃癌遗传易感性的关联分析

Association analysis of DNMT3A/3B promoter SNPs with genetic susceptibility to gastric cancer in Suqian region

目的探讨DNA甲基转移酶3A/3B（DNMT3A/3B）基因启动子区单核苷酸多态性（SNPs）与宿迁地区汉族人群胃癌易感性的关系。方法提取233例胃癌患者及208例体检健康者外周血基因组DNA,用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）结合DNA测序技术检测DNMT3A启动子区-448A〉G位点和DNMT3B启动子区-149C〉T位点在待检人群中的基因频率分布。结果在DNMT3A-448A〉G位点中,AA基因型与GG基因型在胃癌组和对照组中差异有统计学意义（χ~2=9.552,P〈0.05）;A等位基因在胃癌组中的分布高于对照组（χ~2=9.493,P〈0.05）。按年龄分组后在年龄≥50岁组中AA与GG基因型频率差异有统计学意义（χ~2=8.941,P〈0.05）。按性别分组后在男性组中AA与GG基因型频率差异有统计学意义（χ~2=7.105,P〈0.05）。在DNMT3B-149C〉T位点中,胃癌组和对照组中均未检测到CC基因型,基因型以及等位基因在胃癌组和对照组中差异无统计学意义（P〉0.05）,且在年龄、性别分组中基因型频率差异均无统计学意义（P〉0.05）。经危险因素分析,DNMT3A-448A等位基因与胃癌密切相关（OR=1.788,95%CI=1.299~2.460）。结论 DNMT3A-448A〉G与胃癌的遗传易感性有关联,可作为胃癌遗传易感性风险因素。DNMT3B-149C〉T与胃癌的遗传易感性无相关性。

Objective To investigate the association of DNA methyhransferase 3A/3B （DNMT3A/3B） promoter single nucleotide pol- ymorphisms （SNPs） with genetic susceptibility to gastric cancer （GC） in Han population of Suqian region. Methods Genomic DNAs in leukocyte cells of peripheral blood samples from 233 gastric cancer patients and 208 healthy controls were extracted, and the genotype frequencies of DNMT3A promoter -448A 〉 G and DNMT3B promoter -149C 〉 T were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and DNA sequencing analysis. Results There were significant differences in the distributions of genotypes AA and GG in DNMT3A -448A 〉 G between gastric cancer patients and healthy controls （χ2 = 9.552, P 〈 0.05 ）. The frequency of allele A in gastric cancer patients was significantly higher than that in healthy controls （χ2 = 9. 493, P 〈 0.05 ）. When stratified by gender and age, the frequencies of genotype AA and GG in male gastric cancer patients or the patients aged above 50 years old were significantly higher than that in the corresponding healthy controls （χ2 = 7. 105, P 〈 0.05 ; χ2 = 8. 941, P 〈 0.05 ）. However, no genotype CC in DNMT3B -149C 〉 T was detected in gastric cancer patients and healthy controls. There was also no significant difference in the frequencies of genotype and allele between the two groups （ P 〉 0.05 ）, and the genotype frequency was not correlated with age and gender. In addition, the analysis of risk factors showed that DNMT3A..448A allele was closely related to gastric cancer （OR=1.788, 95%CI = 1.299-2.460）. Conclusion DNMT3A-448A 〉G but not DNMT3B-149C 〉T is associated with the genetic susceptibility to gastric cancer, and DNMT3A-448A 〉 G may be a risk factor of gastric cancer.