Association of DNMT1 Gene Polymorphisms in Exons With Sporadic Infiltrating Ductal Breast Carcinoma Among Chinese Han Women in the Heilongjiang Province
Association of DNMT1 Gene Polymorphisms in Exons With Sporadic Infiltrating Ductal Breast Carcinoma Among Chinese Han Women in the Heilongjiang Province
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DNMT1基因外显子多态性与黑龙江省汉族女性散发性浸润性导管癌的相关性
DOI：
10.3816/cbc.2010.n.049
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发表时间：
2010-10-01
影响因子：
3.1
通讯作者：
Li Dianjun
中科院分区：
文献类型：
--
作者：
Gao Xiang;Fu Zhenkun;Li Dianjun
背景资料：浸润性导管癌（IDC）是女性最常见的恶性乳腺癌，遗传因素在IDC的易感性中起重要作用。DNA甲基化的改变是人类癌症（包括乳腺癌）中的表观遗传变化。DNA甲基转移酶1（DNMT 1）是决定基因组甲基化模式的主要酶。为了阐明DNMT 1基因多态性与IDC的关系，在中国东北黑龙江省的妇女中进行了病例对照研究。患者和方法：我们仔细研究了DNMT 1外显子中可能影响DNMT 1活性的2种遗传多态性。我们的研究对象包括305例IDC患者和314名年龄匹配的健康对照。采用聚合酶链反应-限制性片段长度多态性方法进行基因分型。通过SPSS 13.0版和Haploview 4.1版使用卡方检验分析数据。分析DNMT 1基因多态性与IDC临床特征的关系。结果：在rs 16999593中，CT基因型和C等位基因频率在患者组低于对照组（分别为P = 0.028和P = 0.017）。此外，患者的rs 2228611 AG基因型高于对照组（P = .015）。患者单倍型CA的频率低于对照组（P = 0.034）。DNMT 1基因和孕酮受体（PgR）的2个单核苷酸多态性与p53状态之间存在显著关联。DNMT 1基因多态性与肿瘤大小或雌激素受体状态之间无相关性。结论：我们的研究结果提示，DNMT 1基因外显子多态性可能为预测黑龙江省汉族妇女散发性IDC的风险提供有价值的信息，并可能与PgR和p53状态等预后因素相关。
Background: Infiltrating ductal carcinoma (IDC) is the most common malignant breast cancer in women, and genetic factors appear to play a significant role in the susceptibility to IDC. Alteration of DNA methylation is an epigenetic change in human cancers, including breast cancer. DNA-methyltransferase 1 (DNMT1) is a major enzyme that determines genomic methylation patterns. In order to clarify the association of DNMT1 polymorphisms with IDC, a case-control study was conducted in women from the Heilongjiang Province, in the northeast of China. Patients and Methods: We scrutinized the 2 genetic polymorphisms in exons of DNMT1 that may influence the activity of DNMT1. Our research subjects consisted of 305 patients with IDC and 314 age-matched healthy controls. Genotypes were determined by polymerase chain reaction restriction fragment length polymorphism. Data were analyzed using the chi(2) test by SPSS, version 13.0, and Haploview, version 4.1. The association between DNMT1 polymorphisms and the clinical features of IDC was analyzed. Results: In rs16999593, the frequency of CT genotype and C allele were lower in patients than in controls (P = .028 and P = .017, respectively). Also, rs2228611 AG genotype was higher in patients than in controls (P = .015). The frequency of haplotype CA was lower in patients than in controls (P = .034). Significant association was shown between the 2 single nucleotide polymorphisms of the DNMT1 gene and progesterone receptor (PgR) and p53 status. No association was found between DNMT1 gene polymorphisms and tumor size or estrogen receptor status. Conclusion: Our results was a previous study, which suggested that DNMT1 gene polymorphisms in exons may provide valuable information for predicting the sporadic IDC risk and may be associated with prognosis factors such as PgR and p53 status in Chinese Han women in the Heilongjiang Province.