Genetic Association Study of Angiotensin II Receptor Types 1 (A168G) and 2 (T1247G and A5235G) Polymorphisms in Breast Carcinoma among Brazilian Women

Abstract

Background: Many types of cancer are associated with polymorphisms of the renin-angiotensin system. Our aim was to assess possible association between single-nucleotide polymorphisms (SNPs) of the angiotensin II receptor types 1 (A168G), and 2 (T1247G and A5235G) with breast cancer. Patients and Methods: 242 participating subjects were genotyped and allocated to case or control groups. Results: Genotype distribution (in %) was: for AGTR1 (A168G): AA, AG, GG = 61, 30, 09 for cases, and 69, 25, 06 for controls (p = 0.55); for AGTR2 (T1247G): TT, TG, GG = 84, 12, 04 for cases, and 81, 17, 02 for controls (p = 0.45); for AGTR2 (A5235G): AA, AG, GG = 32, 67, 01 for cases, and 53, 28, 19 for controls (p < 0.0001). Women carrying genotypes AA/AG in the intronic region of angiotensin II type 2 receptor had an 11-fold higher risk of breast cancer than GG carriers. Conclusions: Many types of cancer have been associated with polymorphisms of the renin-angiotensin system. For SNP A5235G, the GG genotype seems to be protective against breast cancer. The other 2 SNPs showed no association. However, SNPs T1247G and A5235G were associated with at least 1 clinical variable, with G being a predictor of better outcome. The use of SNPs A5235G and T1247G (the latter to a lesser degree) as genetic markers should be considered.

Role and therapeutic potential of G-protein coupled receptors in breast cancer progression and metastases

“…Individuals harbouring genotypes with one or two copies of these allelic variants were found to be associated with 30% lower risk of BCa as compared to the homozygotes ( Koh et al, 2005 ). Conversely, another independent study showed no significant association between A168G polymorphism of AGTR1 and BCa risk, but demonstrated the significance of AGTR2 SNPs (T1247G and A5235G) as a predictor of BCa in Brazilian women ( Molina Wolgien Mdel et al, 2014 ). Nevertheless, deletion of the 5′ flanking region of AGTR1 showed 20-fold increase in chloramphenicol acetyltransferase reporter activity, thus confirming the presence of a negative regulatory element(s) in the upstream region of AGTR1 ( Takayanagi et al, 1994 ).…”