Laboratorio de Biología Molecular Aplicada, Facultad de Ciencias Exactas, Quimicas y Naturales, Universidad Nacional de Misiones, Posadas, Misiones, Argentina.
Laboratorio de Epidemiología Genética, Dirección de Investigación CEMIC-CONICET, Buenos Aires, Argentina.
J Med Virol. 2022 Feb;94(2):745-751. doi: 10.1002/jmv.27359. Epub 2021 Oct 4.
The province of Misiones is considered a region with a high mortality rate due to cervical cancer (CC). To gain insight into this problem, we explored the association between genetic variation in the E6 and E7 oncogenes of HPV16 and the risk of CC. We studied 160 women with cytological diagnoses of negative for intraepithelial lesion or malignity, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion/CC and a positive test for HPV16 infection. The genetic characterization of E6 and E7 genes was undertaken through PCR amplification and direct Sanger sequencing. Phylogenetic classification was conducted using Bayesian methods. To estimate the odds ratio (OR) for an association between genetic variants in the E6 and E7 genes and the risk of CC, we used ordinal logistic regression adjusted by age. The final data set comprised 112 samples. Diagnostic single-nucleotide polymorphisms (SNPs) and phylogenetic trees confirmed the presence of Lineage A (95.5%) and D (4.5%) in the samples. For the E6 gene, we identified eleven different sequences, with the most common ones being Lineage A E6 350G (58.9%) and E6 350T (37.5%). The E6 350G was associated with progression to HSIL/CC, with an OR of 19.41 (4.95-76.10). The E7 gene was more conserved than E6, probably due to the functional constraints of this small protein. Our results confirmed the association of the E6 350G SNP with a higher risk of developing CC. These data will contribute to understanding the biological bases of CC incidence in this region.
米西奥内斯省被认为是宫颈癌（CC）死亡率较高的地区。为了深入了解这一问题，我们探讨了 HPV16 的 E6 和 E7 癌基因的遗传变异与 CC 风险之间的关联。我们研究了 160 名女性，她们的细胞学诊断结果为阴性上皮内病变或恶性、低级别鳞状上皮内病变和高级别鳞状上皮内病变/CC，以及 HPV16 感染阳性。通过 PCR 扩增和直接 Sanger 测序对 E6 和 E7 基因进行遗传特征分析。使用贝叶斯方法进行系统发育分类。为了估计 E6 和 E7 基因遗传变异与 CC 风险之间的关联的优势比（OR），我们使用按年龄调整的有序逻辑回归进行分析。最终数据集包括 112 个样本。诊断单核苷酸多态性（SNP）和系统发育树证实了样本中存在 A 谱系（95.5%）和 D 谱系（4.5%）。对于 E6 基因，我们鉴定了十一种不同的序列，最常见的是 A 谱系 E6 350G（58.9%）和 E6 350T（37.5%）。E6 350G 与进展为 HSIL/CC 相关，OR 为 19.41（4.95-76.10）。E6 比 E7 更具多态性，这可能是由于该小蛋白的功能限制。我们的结果证实了 E6 350G SNP 与更高的 CC 发病风险之间的关联。这些数据将有助于了解该地区 CC 发病率的生物学基础。
