IRS-2 G1057D polymorphism in Turkish patients with colorectal cancer

Yükseloğlu, Emel Hülya; Çelik, Sevim; Kucuk, Meral Urhan; Yalın, Erdinç; Özkal, Şermin; Ateş, Cengiz; Berköz, Mehmet; Yalın, Serap; Ateş, Nurcan Aras

doi:10.5114/pg.2014.42503

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…Among IRS2 polymorphisms, rs1805097G>A has been evaluated in six studies ( Table 5 ). Three of them have found that rs1805097G>A was not associated with CRC in Caucasian, Turkish and Iranian populations ( 36 , 41 , 45 ). The only significant result reported was in the study conducted by Slattery et al.…”

Section: Resultsmentioning

confidence: 99%

A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility

et al. 2023

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BackgroundThe receptors, ligands, and associated proteins of the insulin-like growth factor (IGF) family are involved in cancer development. The IGF1 receptor and its accompanying signaling cascade are a crucial growth-regulatory mechanism that plays an important role in colorectal cancer (CRC) proliferation and differentiation. IRS1 (Insulin receptor substrate-1), a major substrate for the IGF1R, is involved in cell growth and promotes tumorigenesis. There are shreds of evidence from prior research suggesting that IGF system polymorphisms may influence susceptibility to CRC. However, the findings in this area were contradictory. Accordingly, we carried out a systematic literature search to identify all case-control, cross-sectional, and cohort studies on the association between various polymorphisms across four IGF1 pathway genes (IGF1, IGF1R, IRS1, and IRS2) and the risk of CRC.MethodsWe performed a comprehensive search strategy in PubMed, Scopus, and Web of Science databases for articles available until Aug 30, 2022. A total of 26 eligible studies with IGF1/IGF1R, IRS1 and IRS2 polymorphisms; met the inclusion criteria. All case-control studies for IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A comprising 22,084 cases and 29,212 controls were included in the current meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationships between the polymorphisms and CRC susceptibility. All statistical analyses were performed using STATA software version 14.0.ResultsThe meta-analysis of available data for rs6214C>T, rs1801278G>A, and rs1805097G>A showed a significant association between these polymorphisms and an increased CRC risk in some of the comparisons studied (rs6214C>T, pooled OR for CC = 0.43, 95% CI 0.21- 0.87, P = 0.019; rs1801278G>A, OR for GA = 0.74, 95% CI 0.58-0.94, P = 0.016; rs1805097G>A, OR for GA = 0.83, 95% CI 0.71-0.96, P = 0.013). Nevertheless, the meta-analysis did not include other genetic variations in IGF1, IGF1R, IRS1, and IRS2 due to heterogeneity and limited sample size.ConclusionsThis systematic review and meta-analysis provide evidence that genetic variants in IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A are associated with an increased risk of CRC. These findings may contribute to a better understanding of the complex genetic mechanisms involved in CRC development and could inform future research on prevention and treatment strategies for this disease.

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Section: Resultsmentioning

confidence: 99%

A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility

et al. 2023

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“…A study on Turkish subjects indicated that the variant allele of Asp1057 of IRS2 was associated with endometrial cancer, but they did not identify any influence on ovarian cancer (23,24). Another study in a Turkish population indicated that the IRS2 Gly1057Asp variant was not associated with colorectal cancer (25). On the other hand, a recent meta-analysis study indicated that the Asp1057 variant was associated with a decreased risk of colorectal cancer (26).…”

Section: Discussionmentioning

confidence: 99%

Association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer in Turkish subjects

et al. 2020

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Insulin receptor substrate (IRS) proteins are cytoplasmic adaptors that transmit the signal from the IR and insulin-like growth factor-1 receptor to effector proteins. Overexpression of IRS proteins has been indicated to be linked to cancer development. In addition to their expression profiles, studies have indicated that polymorphisms of IRS1 and IRS2 are also associated with the susceptibility to numerous cancer types. IRS1 Gly972Arg and IRS2 Gly1057Asp are the common variants of these genes. The present study aimed to determine the association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer development. The study included 100 patients with gastric cancer and 100 controls. Single-nucleotide polymorphisms were detected by real-time PCR using Taqman assays. The results suggested that in individuals with the IRS1 Gly/Arg genotype, the odds of having gastric cancer was increased by 7.891-fold (95% CI: 3.251-19.154, P<0.001) and in individuals with the IRS1 Arg/Arg genotype, it was increased by 22.716-fold (95% CI: 6.311-81.761, P<0.001) compared with those with the IRS1 Gly/Gly genotype. Although the IRS2 Gly1057Asp genotype analysis suggested that subjects with the Asp/Asp genotype had a 2,311-fold increased odds of having gastric cancer compared to those with the Gly/Gly genotype, the result was not statistically significant (95% CI: 0.800-6.678, P= 0.122). The combined effects of the IRS1 and IRS2 variants on gastric cancer were also determined. The results suggested that individuals with Gly/Arg+Gly/Asp and Gly/Arg+Asp/Asp genotypes had a higher odds of having gastric cancer compared to individuals of the Gly/Gly+Gly/Gly genotype (P= 0.001 and P= 0.027, respectively). In conclusion, the present results suggested that the IRS1 Gly972Arg and IRS2 Gly1057Asp variations may be associated with an increased susceptibility to develop gastric cancer. Further studies with larger sample sizes are required to support the present results and to explore the use of these variations as a biomarker for gastric cancer.

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“…They only included 4 studies. To date, two studies [ 9 , 11 ] have been reported in recent years since the meta-analysis [ 20 ]. In analysis of all included studies, our meta-analysis found that rs1805097 polymorphism was associated with decreased CRC risk.…”

Section: Discussionmentioning

confidence: 99%

IRS-2 rs1805097 polymorphism is associated with the decreased risk of colorectal cancer

et al. 2017

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Recent studies explored the association between insulin receptor substrate-2 (IRS-2) gene rs1805097 polymorphism and colorectal cancer (CRC) with contradictory findings. Therefore, we conducted a comprehensive meta-analysis by searching the databases of PubMed and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 5 citations containing 6 case-control studies involving 4,333 cases and 5,333 controls were included. Our data indicated that IRS-2 rs1805097 polymorphism was associated with decreased risk of CRC. Stratification analysis of ethnicity found that rs1805097 polymorphism decreased the risk of CRC among Americans. Stratification analysis of cancer type suggested that this polymorphism decreased the risk of colon cancer. In summary, this meta-analysis indicates that IRS-2 gene rs1805097 polymorphism plays an important role in the pathogenesis of CRC.

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IRS-2 G1057D polymorphism in Turkish patients with colorectal cancer

Cited by 6 publications

References 28 publications

A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility

A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility

Association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer in Turkish subjects

IRS-2 rs1805097 polymorphism is associated with the decreased risk of colorectal cancer

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