Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero Chilpancingo, Guerrero Avenida Lázaro Cárdenas, C.P. 39090, Ciudad Universitaria, Chilpancingo, Guerrero, México.
Mol Biol Rep. 2013 Jul;40(7):4275-80. doi: 10.1007/s11033-013-2511-9. Epub 2013 May 16.
Abnormal methylation is related to cancer development. Since DNMT3B is an enzyme that modulates genomic methylation, we hypothesized that genetic variants of the promoter DNMT3B may be associated with an increased risk of developing cervical cancer. Our aim was to investigate the association between -579GT and 46359CT polymorphisms of DNMT3B and cervical cancer, high-grade squamous intraepithelial lesions (HSIL), and low-grade squamous intraepithelial lesions (LSIL). Samples from 200 healthy women and 130 women with squamous intraepithelial lesions (70 with cervical cancer, 30 with HSIL, and 30 with LSIL) were analyzed. Polymorphism genotyping was performed using PCR and restriction fragment length polymorphism. The -579GT polymorphism was not associated with cervical cancer, HSIL, or LSIL. The CT genotype of 46359CT polymorphism was significantly associated with cervical cancer risk (OR 8.75, CI 1.27-374.1), whereas the TT genotype was associated with a significantly decreased risk of HSIL (OR 0.66, CI 0.01-0.32) and LSIL (OR 0.11, CI 0.026-0.45). Our results suggest that genotyping the 46359CT polymorphism in DNMT3B may help identify women who are genetically susceptible to cervical cancer development. Additional studies with larger sample sizes are necessary to confirm our findings.
异常甲基化与癌症的发展有关。由于 DNMT3B 是一种调节基因组甲基化的酶,我们假设启动子 DNMT3B 的遗传变异可能与宫颈癌风险增加有关。我们的目的是研究 DNMT3B 的-579GT 和 46359CT 多态性与宫颈癌、高级别鳞状上皮内病变(HSIL)和低级别鳞状上皮内病变(LSIL)之间的关系。分析了 200 名健康女性和 130 名患有鳞状上皮内病变的女性(70 名宫颈癌、30 名 HSIL 和 30 名 LSIL)的样本。使用 PCR 和限制性片段长度多态性分析了多态性基因分型。-579GT 多态性与宫颈癌、HSIL 或 LSIL 无关。46359CT 多态性的 CT 基因型与宫颈癌风险显著相关(OR 8.75,CI 1.27-374.1),而 TT 基因型与 HSIL(OR 0.66,CI 0.01-0.32)和 LSIL(OR 0.11,CI 0.026-0.45)的风险显著降低相关。我们的结果表明,对 DNMT3B 中的 46359CT 多态性进行基因分型可能有助于识别遗传上易患宫颈癌发展的女性。需要更大样本量的进一步研究来证实我们的发现。