Angiotensinogen, Angiotensin-Converting Enzyme, and Chymase Gene Polymorphisms as Biomarkers for Basal Cell Carcinoma Susceptibility.

INTRODUCTION: 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. METHODS: DNA samples of 203 unrelated Greeks were studied, including 100 patients with BCC and 103 matched healthy controls. RESULTS: 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). CONCLUSIONS: 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.

Association Between a High Gene Expression Variant of Chymase and Increased Risk for Basal Cell Carcinoma.

BACKGROUND/AIM: Previous studies have associated certain variations in genes encoding factors of renin-angiotensin system (RAS), indirectly leading to higher angiotensin II (AngII) levels, with greater risk for basal cell carcinoma (BCC) development. Chymase (CMA1) is the main regulator of the RAS-independent AngII generation pathway and numerous studies have shown its oncogenic potential in several cancer types including BCC. In this study, we investigated the possible association between BCC pathogenesis and the functional DNA polymorphism A1903G (rs1800875) that affects expression of the CMA1 gene. PATIENTS AND METHODS: We genotyped 199 DNA samples, isolated from 100 BCC patients and 99 age, sex, and ethnicity-matched healthy controls for the CMA1 A1903G polymorphism. Genotyping was performed with PCR amplification, followed by MboI enzyme digestion and agarose gel electrophoresis of the resulted DNA fragments. RESULTS: The variant G allele that possibly increases CMA1 gene expression was not detected at a significantly different frequency between the groups of BCC patients and healthy controls. However, the AG heterozygous genotype was significantly increased in BCC patients compared with controls (p<0.001). CONCLUSION: The high expression CMA1 G allele carriers have an increased risk for BCC and elevated levels of chymase in the skin may have a carcinogenic effect.