Association between polymorphisms of the renin–angiotensin system genes and breast cancer risk: a meta-analysis

Abstract

The renin-angiotensin system (RAS) has been considered to be implicated in the development of breast cancer. However, the results are inconsistent. In this study, we conducted a meta-analysis to assess the association between four polymorphisms, including angiotensin I-converting enzyme (ACE) I/D and A240T, angiotensin II type 1 receptor (AGTR1) A1166C and angiotensinogen (AGT) M235T polymorphisms, and breast cancer risk. Published literature from PubMed, ISI web of science, and Embase databases were retrieved. All studies evaluating the association between ACE I/D, ACE A240T, AGTR1 A1166C, or AGT M235T polymorphism and breast cancer risk were included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Ten studies (1,650 cases and 9,283 controls) on ACE I/D polymorphism, six studies (1,316 cases and 2,632 controls) on ACE A240T polymorphism, three studies (235 cases and 601 controls) on AGTR1 A1166C polymorphism, and two studies (273 cases and 3,547 controls) on AGT M235T polymorphism were included. Overall, the meta-analysis showed no significant association between I/D or A240T polymorphism and breast cancer risk in either genetic model. Further subgroup analysis by ethnicity also revealed non-significant association in Caucasian or Asian populations except for Africans (the statistically significant association for ACE I/D or A240T polymorphism in Africans derived from only one study). A marginally significant association was observed for AGTR1 A1166C polymorphism in Caucasians (CC vs. AA: OR = 0.31, 95% CI 0.10-0.99). In addition, there was a significant association between AGT M235T polymorphism and breast cancer risk in Caucasians (OR = 1.45, 95% CI 1.12-1.88). The present meta-analysis suggested that ACE I/D and A240T polymorphisms might not be a good predictor of breast cancer risk, while AGTR1 A1166C and AGT M235T polymorphisms might be implicated in the pathogenesis of breast cancer. Given the limited sample size, the findings warrant further investigation.

Role of ACE and AGT gene polymorphisms in genetic susceptibility to diabetes mellitus type 2 in a Brazilian sample

“…Our findings are in agreement with prior studies that have found an association between this polymorphism and DM2 (Young et al, 1998;Mehri et al, 2010). Additionally, meta-analyses have also reported associations between the A allele of the polymorphism and the risk of cardiovascular diseases Pan, 2012, 2013;Liang et al, 2013a,b;Li et al, 2013;Chen et al, 2014), renal failure (Zhou et al, 2013b), pre-eclampsia (Lin et al, 2012), and breast cancer (Xi et al, 2011). However, a meta-analysis involving Caucasian and Asian individuals failed to detect an association between the rs699 polymorphism and diabetic nephropathy (Ding et al, 2012).…”

Association between the AGTR1 A1166C polymorphism and risk of IgA nephropathy: a meta-analysis

“…Zhang et al (2013) observed that it may be involved in the development of coronary heart disease, while Zhang et al (2011) reported a lack of association with susceptibility to ischemic stroke. In addition, Xi et al (2011) demonstrated that it might be implicated in the pathogenesis of breast cancer, and Ding et al (2012) established its possible contribution to the development of diabetic nephropathy.…”

“…The A1166C polymorphism (rs5186) is located in the 3' untranslated region, and comprises an A to C transversion at nucleotide 1166. Previous studies have demonstrated that this sequence variation is associated with susceptibility to coronary heart disease, breast cancer, and diabetic nephropathy (Xi et al, 2011;Ding et al, 2012;Zhang et al, 2013). However, little is known regarding the association between the AGTR1 gene A1166C polymorphism and susceptibility to IgAN.…”

Association of angiotensin ІІ type 1 receptor (A1166C) polymorphism with breast cancer risk: An update meta-analysis

“…This study is an update meta-analysis in which the results were different from the previous one. 25 Previous studies suggested that the RAS plays an important role in the regulation of cell proliferation, angiogenesis, and inflammation, 27,28 which indicated that RAS genes might be implicated in the carcinogenesis.…”

“…25 However, there are several studies that had not been included in their meta-analysis. In the present study, we included five case-control studies to perform a meta-analysis.…”