DNMT3A rs36012910 A>G polymorphism and gastric cancer susceptibility in a Chinese population
DNMT3A rs36012910 A>G polymorphism and gastric cancer susceptibility in a Chinese population
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DOI：
10.1007/s11033-012-1996-y
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发表时间：
2012-10
影响因子：
2.8
通讯作者：
Qunying Wu;Sen Lu;Ling Wang;Jiaojiao Hu;Fengchang Qiao;X. Qiu;Chengcheng Zhao;Yingbin Lao;Yunwei Song;H. Fan
中科院分区：
文献类型：
--
作者：
Qunying Wu;Sen Lu;Ling Wang;Jiaojiao Hu;Fengchang Qiao;X. Qiu;Chengcheng Zhao;Yingbin Lao;Yunwei Song;H. Fan
DNA甲基转移酶（DNMT）-3A在胚胎发育和DNA甲基化异常在肿瘤发生中起着至关重要的作用。DNMT 3A基因的多态性可能影响其酶活性及其对癌症易感性的贡献。本研究评估了DNMT 3A rs36012910 A>G与中国人群胃癌（GC）易感性的相关性。从340例胃癌患者和251例健康对照者的样本中提取基因组DNA。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测所有受试者DNMT 3A rs36012910 A>G基因型频率，并经测序证实。分层分析用于研究年龄和性别亚组，并评估rs36012910 A>G多态性与GC遗传易感性的关联。所有患者和对照个体均成功进行了DNMT 3A rs36012910 A>G多态性基因分型。DNMT 3A rs36012910等位基因G在健康个体和GC患者中的频率分别为3.39%和7.78%。GC组rs36012910 AG基因型明显多于对照组，而rs36012910 GG基因型仅见于1例。进一步分层发现AG+GG基因型与60岁以上男性胃癌易感性相关，但该多态性与女性胃癌易感性无显著相关性。携带AG+GG基因型的男性个体患GC的风险是携带AA基因型的男性个体的2.362倍。与rs36012910等位基因A相比，rs36012910等位基因G与GC风险增加相关。这是第一个报告，调查的分布和评估一个罕见的SNP在DNMT 3A与遗传易感性GC的关联。DNMT 3A rs36012910 A>G可能成为用于GC预测的潜在生物标志物，但需要在更大群体和不同人群中进行进一步研究以确认。
DNA-methyltransferase (DNMT)-3A plays a crucial role in embryonic development and aberrant DNA methylation in carcinogenesis. Polymorphisms of the DNMT3A gene may influence its enzymatic activity and its contribution to susceptibility to cancer. This study evaluated the association of DNMT3A rs36012910 A>G with susceptibility to gastric cancer (GC) in a Chinese population. Genomic DNA was extracted from samples taken from 340 patients with GC and 251 healthy control subjects. The genotype frequency of DNMT3A rs36012910 A>G in all subjects was detected by polymerase chain reaction–restriction fragment length polymorphism and confirmed by sequencing. Stratification analyses were used to study subgroups by age and gender and to evaluate the association of rs36012910 A>G polymorphism with genetic susceptibility to GC. All patients and control individuals were successfully genotyped for the DNMT3A rs36012910 A>G polymorphism. The frequency of DNMT3A rs36012910 allele G is 3.39 % in healthy individuals and 7.78 % in GC patients, respectively. The rs36012910 AG genotype was significantly more common in the GC group than in the controls, although the rs36012910 GG genotype was only one case in GC patients. Further stratification indicated that AG+GG genotypes were associated with susceptibility to GC in males older than 60, but this polymorphism has no significant association with GC susceptibility in females. Male individuals who carried AG+GG genotypes had a 2.362-fold increased risk of GC compared to those who carried the AA genotype. The rs36012910 allele G was associated with an increased risk of GC compared to the rs36012910 allele A. This is the first report to investigate the distribution and evaluate the association of a rare SNP in DNMT3A with genetic susceptibility to GC. DNMT3A rs36012910 A>G might become a potential biomarker for use in GC prediction, although further studies in larger groups and different populations are needed for confirmation.