Yapijakis Christos, Gintoni Iphigenia, Charalampidou Sevastiana, Angelopoulou Antonia, Papakosta Veronica, Vassiliou Stavros, Chrousos George P
Unit of Orofacial Genetics, 1st Department of Pediatrics, National Kapodistrian University of Athens, "Hagia Sophia" Children's Hospital, Athens, Greece.
Department of Molecular Genetics, Cephalogenetics Center, Athens, Greece.
Adv Exp Med Biol. 2023;1423:175-180. doi: 10.1007/978-3-031-31978-5_14.
The intake of angiotensin-converting enzyme (ACE) inhibitors and specific antagonists of angiotensin II receptors, widely used as antihypertensive drugs, significantly reduces the risk of developing basal cell carcinoma (BCC), highlighting the possible tumorigenic role of angiotensin II (AngII). We present here the investigated genetic association between the development of BCC and functional DNA polymorphisms M235T, I/D, and A1903G in the genes of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and chymase (CMA1), which mediate AngII production levels.
DNA samples of 203 unrelated Greeks were studied, including 100 patients with BCC and 103 matched healthy controls.
The MT genotype of the AGT-M235T polymorphism was significantly more prevalent in the patient group (78.0%) versus the healthy control group (28.3%; p < 0.001). The DD genotype of the ACE-I/D polymorphism was also increased in BCC patients (72.8%) compared to controls (46.2%; p = 0.001). The heterozygous AG genotype of CMA1-A1903G was significantly more frequent in the BCC group (86%) than in the healthy controls (50.5%; p < 0.001).
The MT, DD, and AG genotypes of the AGT- M235T, ACE-I/D, and CMA1-A1903G polymorphisms, respectively, were significantly increased in frequency within the group of cancer patients compared to the healthy controls. All three genotypes correspond to increased enzyme levels or activity and result in increased levels of AngII; therefore, they may be potentially utilized as reliable biomarkers associated with an individual's increased risk for BCC development.
血管紧张素转换酶（ACE）抑制剂和血管紧张素II受体特异性拮抗剂作为抗高血压药物被广泛使用，它们能显著降低基底细胞癌（BCC）的发生风险，这凸显了血管紧张素II（AngII）可能的致瘤作用。我们在此展示了对BCC发生与血管紧张素原（AGT）、血管紧张素转换酶（ACE）和糜酶（CMA1）基因中功能性DNA多态性M235T、I/D和A1903G之间的遗传关联研究，这些基因介导AngII的产生水平。
对203名无亲缘关系的希腊人的DNA样本进行了研究，其中包括100例BCC患者和103名匹配的健康对照。
与健康对照组（28.3%；p < 0.001）相比，AGT-M235T多态性的MT基因型在患者组中显著更常见（78.0%）。与对照组（46.2%；p = 0.001）相比，BCC患者中ACE-I/D多态性的DD基因型也有所增加。CMA1-A1903G的杂合AG基因型在BCC组（86%）中比健康对照组（50.5%；p < 0.001）显著更频繁。
与健康对照组相比，AGT-M235T、ACE-I/D和CMA1-A1903G多态性的MT、DD和AG基因型在癌症患者组中的频率分别显著增加。所有这三种基因型都对应着酶水平或活性的增加，并导致AngII水平升高；因此，它们可能潜在地用作与个体患BCC风险增加相关的可靠生物标志物。
