Inácio Ângela, Aguiar Laura, Rodrigues Beatriz, Pires Patrícia, Ferreira Joana, Matos Andreia, Mendonça Inês, Rosa Raquel, Bicho Manuel, Medeiros Rui, Bicho Maria Clara
Laboratório de Genética, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Instituto de Saúde Ambiental (ISAMB) e Laboratório Associado TERRA, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Antioxidants (Basel). 2023 Sep 27;12(10):1806. doi: 10.3390/antiox12101806.
Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: , , , , , , , , , and . Notably, the gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype () and DD genotype () were shown to increase the risk of HPV infection, and the interaction between BB () and 0.0 () was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.
人乳头瘤病毒(HPV)感染是浸润性宫颈癌(ICC)和高级别上皮内病变(HSIL)发生的必要但非充分因素。已知氧化应激在HPV感染和致癌过程中起关键作用。在本研究中,我们通过探索氧化应激相关基因:[此处原文缺失具体基因名称],全面研究了HPV感染、HSIL和ICC以及ICC的调控情况。值得注意的是,[此处原文缺失具体基因名称]基因成为一个突出因素,I等位基因的存在可提供针对HPV感染的保护作用。[此处原文缺失具体基因名称]与HPV感染的关联表现为4a等位基因具有保护作用。[此处原文缺失具体基因名称]无效突变体的存在与对HPV感染、HSIL和ICC以及ICC的易感性增加相关。本研究还揭示了一些基因之间有趣的上位性相互作用,进一步突出了它们在疾病调控中的作用。确实,BB基因型([此处原文缺失具体内容])和DD基因型([此处原文缺失具体内容])之间的上位性相互作用显示会增加HPV感染风险,BB([此处原文缺失具体内容])和0.0([此处原文缺失具体内容])之间的相互作用与HPV感染和宫颈病变相关。这些发现强调了四个氧化应激相关基因在HPV相关宫颈病变和癌症发展中的关键作用,丰富了我们对疾病表现遗传影响的临床认识。对这些基因变异的认识具有潜在的临床意义。