Association of the PTEN IVS4 (rs3830675) gene polymorphism with reduced risk of cancer: evidence from a meta-analysis.

Raju K Mandal,Mohammad Irshad,Shafiul Haque,Naseem Akhter,Arif Ali,Aditya K Panda

doi:10.7314/apjcp.2015.16.3.897

Raju K Mandal, Mohammad Irshad + Show 4 more

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https://doi.org/10.7314/apjcp.2015.16.3.897

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Abstract

PTEN (phosphatase and tensin homologue), as a tumor suppressor gene, plays a significant role in regulating cell growth, proliferation, and apoptosis. Results from published studies for association between the PTEN IVS4 I/D (rs3830675) polymorphism and cancer risk are inconsistent and inconclusive. We therefore conducted a meta-analysis to evaluate the potential association between PTEN IVS4 I/D polymorphism and risk of cancer in detail. We searched PubMed (Medline) and EMBASE web databases to cover all relevant studies published until December 2013. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to appraise the strength of association. A total of 1,993 confirmed cancer cases and 3,200 controls were included from six eligible case-control studies. Results from overall pooled analysis suggested a significant effect of the PTEN IVS4 I/D polymorphism and cancer risk in all genetic models, i.e., allele (I vs D: OR=0.743, 95%CI=0.648 to 0.852, p=0.001), homozygous (II vs DD: OR=0.673, 95%CI=0.555 to 0.816, p=0.001), heterozygous (ID vs DD: OR=0.641, 95%CI=0.489 to 0.840, p=0.001), dominant (II+ID vs DD: OR=0.626, 95%CI=0.489 to 0.802, p=0.001) and recessive (II vs DD+ID: OR=0.749, 95%CI=0.631 to 0.889, p=0.001). Significant publication bias was detected during the analysis. The present meta-analysis suggests that the PTEN IVS4 I/D polymorphism is significantly associated with reduced risk of cancer. However, future larger studies with other groups of populations are warranted to clarify this association.

Highlights

Cancer is a polygenic disease, which results from complex interactions between environmental and genetic factors (Pharoah et al, 2004)
Results from overall pooled analysis suggested a significant effect of the PTEN IVS4 I/D polymorphism and cancer risk in all genetic models, i.e., allele (I vs D: odds ratios (ORs)=0.743, 95% confidence intervals (95%CIs)=0.648 to 0.852, p=0.001), homozygous (II vs DD: OR=0.673, 95%CI=0.555 to 0.816, p=0.001), heterozygous (ID vs DD: OR=0.641, 95%CI=0.489 to 0.840, p=0.001), dominant (II+ID vs DD: OR=0.626, 95%CI=0.489 to 0.802, p=0.001) and recessive (II vs DD+ID: OR=0.749, 95%CI=0.631 to 0.889, p=0.001)
It has been widely accepted that genetic factors play an important role in the etiology of cancer and several low penetrance genes are involved in the progression of cancer

Summary

Introduction

Cancer is a polygenic disease, which results from complex interactions between environmental and genetic factors (Pharoah et al, 2004). It remains a major global health problem and leads to increase morbidity and mortality worldwide (Jemal et al, 2011). Epidemiological studies continue to indicate the significant contribution of ‘single nucleotide polymorphisms (SNPs)’ to cancer susceptibility through interaction with various environmental factors (Lichtenstein et al, 2000). It can be anticipated that the discovery of genetic factors of host for cancer risk would assist in the therapeutic applications and overall control of this lethal disease

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