Zhao Zhujiang, Li Can, Song Yunwei, Wu Qunying, Qiao Fengchang, Fan Hong
Department of Genetics and Development, Southeast University Medical School, and Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009.
Oncol Lett. 2012 Feb;3(2):450-454. doi: 10.3892/ol.2011.488. Epub 2011 Nov 17.
The DNA methyltransferase 3A (DNMT3A) -448A>G polymorphism is a novel functional single nucleotide polymorphism (SNP) that contributes to the genetic susceptibility to gastric cancer. In this study, we aimed to assess the genotype frequencies of DNMT3A -448A>G in colorectal cancer (CRC) patients and healthy control subjects, and to explore the association of the DNMT3A functional SNP, -448A>G, with genetic susceptibility to CRC. Genomic DNA was extracted from samples of 258 patients with CRC and 280 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was employed to assess the genotype frequencies of DNMT3A -448A>G in all of the subjects. Stratification analyses were used to study subgroups of subjects by age and gender, and to evaluate the association between the DNMT3A -448A>G polymorphism and the genetic susceptibility to CRC. The allele frequency of -448A among CRC patients and the controls was 26.4 versus 19.8%, respectively. Overall, we found that compared with GG carriers, the DNMT3A -448AA homozygotes had a 3.692-fold increased risk of CRC. Stratification analysis showed a significant difference in this SNP between the CRC patients and the control subjects of different genders. AA homozygotes carried an increased risk in the subgroup of individuals aged ≥50 years in male CRC. Compared with GG homozygotes in females aged ≥50 years, the AG and AA genotypes carried a 0.355-fold decreased risk in this subgroup. These data imply that the DNMT3A SNP -448A>G contributes to genetic susceptibility to CRC. -448A>G may be used as a stratification marker to predict the susceptibility of certain individuals to CRC, particularly in male individuals aged ≥50 years.
DNA甲基转移酶3A（DNMT3A）-448A>G多态性是一种新型功能性单核苷酸多态性（SNP），它与胃癌的遗传易感性有关。在本研究中，我们旨在评估结直肠癌（CRC）患者和健康对照者中DNMT3A -448A>G的基因型频率，并探讨DNMT3A功能性SNP -448A>G与CRC遗传易感性之间的关联。从258例CRC患者和280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分析来评估所有受试者中DNMT3A -448A>G的基因型频率。分层分析用于按年龄和性别研究受试者亚组，并评估DNMT3A -448A>G多态性与CRC遗传易感性之间的关联。CRC患者和对照者中-448A的等位基因频率分别为26.4%和19.8%。总体而言，我们发现与GG携带者相比，DNMT3A -448AA纯合子患CRC的风险增加了3.692倍。分层分析显示，该SNP在不同性别的CRC患者和对照者之间存在显著差异。在男性CRC患者年龄≥50岁的亚组中，AA纯合子的风险增加。与年龄≥50岁女性的GG纯合子相比，AG和AA基因型在该亚组中的风险降低了0.355倍。这些数据表明，DNMT3A SNP -448A>G与CRC的遗传易感性有关。-448A>G可作为一种分层标志物，用于预测某些个体患CRC的易感性，尤其是年龄≥50岁的男性个体。
