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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 9  |  Page : 375-380

Relationship between angiotensin-converting enzyme insertion/deletion gene polymorphism and prostate cancer susceptibility


1 Department of Urology Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
2 Department of Nephrology, Huadu District People's Hospital, Southern Medical University, Guangzhou, China
3 Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China

Date of Web Publication29-Jun-2018

Correspondence Address:
Tian-Biao Zhou
Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat.sen University, Guangzhou 510655
China
Zong-Pei Jiang
Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.171366

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 > Abstract 


Background and Objective: Investigations on the relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and prostate cancer risk are conflicting. This meta-analysis was conducted to assess the relationship between ACE I/D gene polymorphism and prostate cancer risk.
Materials and Methods: Reports were identified from PubMed, Cochrane Library, and China Biological Medicine (CBM)-disc (CBM database) on December 30, 2014, and eligible studies were recruited.
Results: ACE I/D gene polymorphism was not associated with prostate cancer risk for overall populations in this meta-analysis (D allele: Odds ratio [OR] =1.56, 95% confidence interval [95% CI]: 1.00–2.46, P = 0.05; DD genotype: OR = 1.74, 95% CI: 0.95–3.20, P = 0.07; II genotype: OR = 0.67, 95% CI: 0.39–1.15, P = 0.15). Furthermore, the association of ACE I/D gene polymorphism with colorectal cancer risk was not found for the Caucasians. Interestingly, ACE I/D gene polymorphism was associated with prostate cancer risk for the Asian population and Latino population.
Conclusions: There was an association between ACE I/D gene polymorphism and prostate cancer risk for the Asians and Latino population in this meta-analysis. However, more investigations should be performed to confirm this relationship.

Keywords: Angiotensin-converting enzyme, gene polymorphism, insertion/deletion, meta-analysis, prostate cancer


How to cite this article:
Wang ZY, Li HY, Jiang ZP, Zhou TB. Relationship between angiotensin-converting enzyme insertion/deletion gene polymorphism and prostate cancer susceptibility. J Can Res Ther 2018;14, Suppl S2:375-80

How to cite this URL:
Wang ZY, Li HY, Jiang ZP, Zhou TB. Relationship between angiotensin-converting enzyme insertion/deletion gene polymorphism and prostate cancer susceptibility. J Can Res Ther [serial online] 2018 [cited 2019 Jul 17];14:375-80. Available from: http://www.cancerjournal.net/text.asp?2018/14/9/375/171366




 > Introduction Top


Renin-angiotensin-aldosterone system (RAAS), an enzymatic cascade functioning in a paracrine and autocrine fashion, and participated by kidney, liver, vascular endothelium, and adrenal cortex, and counter-regulated by cardiac endocrine function, is a complex endocrine system regulating systemic functions.[1],[2] Angiotensin-converting enzyme (ACE) is one of the most important members of the RAAS family, and ACE insertion/deletion (I/D) gene polymorphism is detected to be associated with the cancers risk. The current evidences indicate that some gene polymorphisms are associated with the prostate cancer risk.

Prostate cancer is the second-paramount leading cause of tumor mortality among males in the Western societies.[3] Approximately 30,000 men die each year of castration-resistant prostate cancer due to the inevitable progression of resistance to the first-line treatment with docetaxel.[4] However, there was no good biomarker to predict the risk of prostate cancer in the past decades.

The present epidemiologic investigations studying the relationship between ACE I/D gene polymorphism and the prostate cancer risk are conducted. The evidence from meta-analysis might be powerful compared with the individual study. We performed this meta-analysis to investigate whether the ACE I/D gene polymorphism was associated with the prostate cancer risk.


 > Materials and Methods Top


Search strategy for the evaluation of the relationship between angiotensin-converting enzyme insertion/deletion gene polymorphism and prostate cancer risk

Relevant studies were searched from the electronic databases of PubMed, Cochrane Library, and China Biological Medicine (CBM)-disc (CBM database) on December 30, 2014. The retrieval strategy of “(prostate cancer or prostate carcinoma) and (ACE)” was entered in these databases.

Inclusion and exclusion criteria

Inclusion criteria

  • The outcome in the included study had to be prostate cancer
  • There had to be at least two comparison groups (case group vs. control group)
  • The investigation should provide the data of ACE I/D genotype distribution.


Exclusion criteria

  • Review articles and editorials
  • Case reports
  • Preliminary result not on ACE I/D gene polymorphism or outcome
  • Investigating the role ACE gene expression to disease
  • If multiple publications for the same data from the same study group occurred, the later paper was recruited into our final analysis.


Data extraction and synthesis

Following information from each eligible investigation was extracted independently by two investigators: First author's surname, year of publication, location of the study performed, ethnicity, control source of the control group, and the number of cases and controls for ACE I/D genotypes. The results were compared, and disagreement was resolved by discussion.

Statistical analysis

Cochrane Review Manager Version 5 (RevMan, Oxford, UK) was used to calculate the available data from each investigation. The pooled statistic was counted using the fixed effects model, but a random effects model was conducted when the P value of heterogeneity test was <0.1.[5],[6] Results were expressed as odds ratios (ORs) for dichotomous data, and 95% confidence intervals (95% CIs) were also calculated. P < 0.05 was required for the pooled OR to be statistically significant.[7],[8]I2 was used to test the heterogeneity among the included studies.


 > Results Top


Study characteristics

Five investigations [9],[10],[11],[12],[13] reporting the relationship between ACE I/D gene polymorphism and prostate cancer were recruited into this meta-analysis. The data of our interest were extracted for the meta-analysis [Table 1].
Table 1: Characteristics of the studies evaluating the effects of ACE I/D gene polymorphism with prostate cancer risk

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Relationship between angiotensin-converting enzyme insertion/deletion gene polymorphism and prostate cancer risk

ACE I/D gene polymorphism was not associated with prostate cancer risk for overall populations in this meta-analysis [D allele: OR = 1.56, 95% CI: 1.00–2.46, P = 0.05; DD genotype: OR = 1.74, 95% CI: 0.95–3.20, P = 0.07; II genotype: OR = 0.67, 95% CI: 0.39–1.15, P = 0.15; [Figure 1] and [Table 2].
Figure 1: Association of angiotensin-converting enzyme insertion/deletion gene polymorphism with prostate cancer risk in overall population

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Table 2: Meta-analysis of the association of ACE I/D gene polymorphism with prostate cancer risk

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In the sub-group analysis according to ethnicity, the association of ACE I/D gene polymorphism with prostate cancer risk was also not found in the Caucasian population in this meta-analysis [D allele: OR = 1.16, 95% CI: 0.74–1.82, P = 0.51; DD genotype: OR = 1.16, 95% CI: 0.69–1.96, P = 0.58; II genotype: OR = 0.92, 95% CI: 0.68–1.23, P = 0.57; [Figure 2] and [Table 2].
Figure 2: Association of angiotensin-converting enzyme insertion/deletion gene polymorphism with prostate cancer risk in the Caucasian population

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In the Asian population, the ACE I/D gene polymorphism was also associated with prostate cancer risk in this meta-analysis [D allele: OR = 1.83, 95% CI: 1.41–2.38, P < 0.00001; DD genotype: OR = 2.63, 95% CI: 1.67–4.16, P < 0.0001; II genotype: OR = 0.53, 95% CI: 0.36–0.80, P = 0.002; [Figure 3] and [Table 2].
Figure 3: Association of angiotensin-converting enzyme insertion/deletion gene polymorphism with prostate cancer risk in the Asian population

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In the Latino population, the ACE I/D gene polymorphism was also associated with prostate cancer risk in this meta-analysis [D allele: OR = 5.11, 95% CI: 1.93–13.53, P = 0.001; DD genotype: OR = 5.14, 95% CI: 1.45–18.22, P = 0.01; II genotype: OR = 0.05, 95% CI: 0.00–0.97, P = 0.05; [Figure 4] and [Table 2].
Figure 4: Association of angiotensin-converting enzyme insertion/deletion gene polymorphism with prostate cancer risk in the Latino population

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 > Discussion Top


The relationship between ACE I/D gene polymorphism and prostate cancer risk was assessed in this meta-analysis. ACE D allele, DD genotype, and II genotype were not associated with prostate cancer risk for overall population and in the Caucasians. The association of ACE I/D gene polymorphism with prostate cancer risk was found in the Asian population and Latino population. However, there was only one study recruited into this meta-analysis for the Asian population and Latino population, and the results might be less robust. More investigations should be conducted to confirm this relationship in the Asian population and Latino population in the future.

In the past, Xie et al.[14] conducted a meta-analysis and reported that ACE D allele, DD genotype, and II genotype were not associated with prostate cancer risk. In this meta-analysis, the number of included studies was larger than that in Xie et al.[14] Moreover, we also performed the sub-group analysis according to ethnicity. The association of ACE I/D gene polymorphism with prostate cancer risk was found in the Asian population and Latino population.

This study used meta-analysis method to evaluate the relationship between ACE I/D gene polymorphism and the prostate cancer risk. No association between ACE I/D gene polymorphism and prostate cancer risk was found in overall population and the Caucasians. Interestingly, ACE I/D gene polymorphism was associated with prostate cancer risk in the Asian population and Latino population. However, those results should be regarded cautiously for the reason of many other ingredients, such as, heterogeneity of enrolled cases, small sample size of the included report, variable study designs, limited statistical power, and different interventions, were closely related to affect the conclusion.


 > Conclusions Top


There was an association between ACE I/D gene polymorphism and prostate cancer risk for the Asians and Latino population in this meta-analysis. However, more investigations should be performed to confirm this association.

Acknowledgments

This study was supported by the Guangzhou Medical Key Subject Construction Project (2013–2015).

Financial support and sponsorship

This study was supported by the Guangzhou Medical Key Subject Construction Project (2013–2015).

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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