<abstract xmlns="http://www.w3.org/1999/xhtml">
<sec id="j_raon-2022-0031_s_006">
<h3>Background</h3>
<p>AKT, also called protein kinase B, is a serine-threonine kinase that functions as a mediator of PI3K-Akt-mTOR signaling pathway and plays an important role in an array of cellular processes. Many single nucleotide polymorphisms (SNP) in <italic>AKT</italic> gene have been observed to be associated with various types of cancers. In the current research the association of a functional SNP rs1130233 in <italic>AKT</italic>, depicting G to A transition, was studied with AKT activation, DNA damage, an early response B-cell translocation gene 2 (Btg2) expression and risk of colorectal cancer (CRC) development.</p></sec>
<sec id="j_raon-2022-0031_s_007">
<h3>Patients and methods</h3>
<p>A total 197 population-based controls and 200 CRC patients were genotyped for SNP rs1130233. AKT expression, activation and <italic>BTG2</italic> expression were determined in GG, AG and AA genotype carriers. DNA damage was determined through comet assay.</p></sec>
<sec id="j_raon-2022-0031_s_008">
<h3>Results</h3>
<p>The heterozygous AG genotype (55.67%) was more prevalent in the local population compared to homozygous wild type GG (37.78%) and homozygous AA genotypes (6.55%). Moreover, AG and AA alleles were observed to be significant contributors (P = 0.01, OR = 1.80, CI = 1.18 to 2.74, and P = 0.001, OR = 5.00, CI = 1.90 to 13.18, respectively) in increasing the risk of CRC. The immunoblot analysis revealed that G to A transition decreased the expression and activation of AKT. Moreover, AG and AA genotypes of <italic>AKT1</italic> rs1130233 showed a significant increase in DNA damage and Btg2 expression.</p></sec>
<sec id="j_raon-2022-0031_s_009">
<h3>Conclusions</h3>
<p>The data concludes that G to A substitution is a risk factor for CRC development involving a decrease in AKT expression and activation and increase in DNA damage.</p></sec>
</abstract>

Background
AKT, also called protein kinase B, is a serine-threonine kinase that functions as a mediator of PI3K-Akt-mTOR signaling pathway and plays an important role in an array of cellular processes. Many single nucleotide polymorphisms (SNP) in AKT gene have been observed to be associated with various types of cancers. In the current research the association of a functional SNP rs1130233 in AKT, depicting G to A transition, was studied with AKT activation, DNA damage, an early response B-cell translocation gene 2 (Btg2) expression and risk of colorectal cancer (CRC) development.

Patients and methods
A total 197 population-based controls and 200 CRC patients were genotyped for SNP rs1130233. AKT expression, activation and BTG2 expression were determined in GG, AG and AA genotype carriers. DNA damage was determined through comet assay.

Results
The heterozygous AG genotype (55.67%) was more prevalent in the local population compared to homozygous wild type GG (37.78%) and homozygous AA genotypes (6.55%). Moreover, AG and AA alleles were observed to be significant contributors (P = 0.01, OR = 1.80, CI = 1.18 to 2.74, and P = 0.001, OR = 5.00, CI = 1.90 to 13.18, respectively) in increasing the risk of CRC. The immunoblot analysis revealed that G to A transition decreased the expression and activation of AKT. Moreover, AG and AA genotypes of AKT1 rs1130233 showed a significant increase in DNA damage and Btg2 expression.

Conclusions
The data concludes that G to A substitution is a risk factor for CRC development involving a decrease in AKT expression and activation and increase in DNA damage.

Impact of <italic>AKT1</italic> polymorphism on DNA damage, <italic>BTG2</italic> expression, and risk of colorectal cancer development

Radiology and Oncology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Impact of  polymorphism on DNA damage,  expression, and risk of colorectal cancer development

Background
AKT, also called protein kinase B, is a serine-threonine kinase that functions as a mediator of PI3K-Akt-mTOR signaling pathway and plays an...

Impact of AKT1 polymorphism on DNA damage, BTG2 expression, and risk of colorectal cancer development

Article Category: research article

Published Online: Aug 14, 2022

Page range: 336 - 345

Received: Feb 27, 2022

Accepted: Jul 03, 2022

DOI: https://doi.org/10.2478/raon-2022-0031

© 2022 Hina Zubair, Zahid Khan, Muhammad Imran, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.