Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with decreased risk for basal cell car
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ORIGINAL PAPER
Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with decreased risk for basal cell carcinoma Christos Yapijakis • Nikolas Koronellos • Sofia Spyridonidou • Antonis Vylliotis Dimitris Avgoustidis • Nikolaos Goutas • Dimitris Vlachodimitropoulos • Eleftherios Vairaktaris
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Received: 31 October 2012 / Revised: 19 December 2012 / Accepted: 20 December 2012 / Published online: 9 January 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Abstract The incidence of basal cell carcinoma (BCC) is significantly reduced in individuals treated with inhibitors of angiotensin I-converting enzyme (ACE) that produces angiotensin II. The objective of this study was to investigate the possible association of a functional polymorphism in the ACE gene, which affects its transcription, with risk for BCC. In DNA samples of 92 patients with BCC and 103 healthy controls of Greek origin and comparable age and gender, we studied the ACE gene insertion/deletion (I/D) polymorphism. Fisher’s exact test was used for comparison of allele and genotype frequencies between the control and patients’ groups. The detected low expression I allele frequency in the group of BCC patients was significantly decreased compared to controls (15.8 vs. 31.1 %, respectively; P = 0.001). ID heterozygotes exhibited 3.06 times lower BCC risk, compared with DD homozygotes (P = 0.001; OR = 0.327, 95 % CI = 0.174–0.615). The protective role of I allele was particularly prominent in women (P = 0.007, OR = 0.299, 95 % CI = 0.125–0.716), while for men it exhibited a marginal level (P = 0.041). These findings indicate that the low expression ACE I allele carriers have a decreased risk for BCC. The protective effect of the ID genotype against BCC C. Yapijakis (&) N. Koronellos S. Spyridonidou A. Vylliotis D. Avgoustidis E. Vairaktaris Department of Oral and Maxillofacial Surgery, University of Athens Medical School, ‘‘Attikon’’ Hospital, Rimini 1, 12461 Athens, Greece e-mail: [email protected] C. Yapijakis Department of Neurology, University of Athens Medical School, ‘‘Eginition’’ Hospital, Athens, Greece N. Goutas D. Vlachodimitropoulos Department of Histopathology, University of Athens Medical School, ‘‘Evgenidion’’ Hospital, Athens, Greece
may be explained by a possible underlying mechanism involving the effect of produced angiotensin II levels on its receptors due to putatively different binding affinity. Keywords Angiotensin I-converting enzyme Angiotensin receptors Basal cell carcinoma Insertion/deletion polymorphism Cancer risk
Introduction Basal cell carcinoma (BCC) is the most common malignant neoplasia accounting for about 75 % of all skin cancers in light-skinned populations, with an annual incidence of several million new cases worldwide [14, 32, 36–38]. Because of its high incidence, BCC is a major burden on health care, despite the fact that it is curable in its early phase if the diagnosis is made promptly [12]. Basal cell carcinogenesis is a multistep process occurring mainly due to
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