angiotensinogen and Carcinoma--Basal-Cell

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.

Topics: Angiotensin II; Angiotensinogen; Biomarkers; Carcinoma, Basal Cell; Chymases; DNA; Genotype; Humans; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Renin-Angiotensin System; Serine Proteases; Skin Neoplasms

Basal cell carcinoma (BCC) has been genetically associated with an increased expression of angiotensin-converting enzyme (ACE), an important factor of the renin-angiotensin system which produces vasoconstrictor angiotensin II. Other factors of this system include angiotensinogen (AGT) and angiotensin receptors AGTR1, AGTR2. We investigated the possible association of BCC with genetic variability in the AGT, AGTR1 and AGTR2 genes.. DNA samples of 190 Greeks were studied, including 91 patients with BCC and 99 matched healthy controls. Molecular genotyping of patients and controls was performed for the polymorphisms AGT M235T, AGTR1 A1166C and AGTR2 G1675A.. The mutant T allele that increases AGT gene expression was detected in two-fold increased frequency in BCC patients in comparison to healthy controls (p <0.001). On the contrary, no significant difference was observed in AGTR1 and AGTR2 variants between patients and controls.. Increased expression of AGT may be associated with BCC.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Angiotensinogen; Carcinoma, Basal Cell; Case-Control Studies; Cell Line, Tumor; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Skin Neoplasms