Genetic variants in the WNT signaling pathway are protectively associated with colorectal cancer in a Saudi population

Parine, Narasimha Reddy; Azzam, Nahla; Shaik, Jilani Purusottapatnam; Aljebreen, Abdulrahman; Alharbi, Othman; Almadi, Majid A; Alanazi, Mohammad; Khan, Zahid

doi:10.1016/j.sjbs.2018.05.018

Cited by 11 publications

(8 citation statements)

References 16 publications

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“…have analyzed the association of polymorphic variants in β-CDC genes with colorectal cancer, and controversial results were observed for the APC gene (Menendez et al 2004;Theodoratou et al 2008;Picelli et al 2010;Li et al 2017;Parine et al 2019). Polymorphisms in the DVL2, AXIN1, and AXIN2 genes have not been analyzed in CRC patients.…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms in APC, DVL2, and AXIN1 Are Associated with Susceptibility, Advanced TNM Stage or Tumor Location in Colorectal Cancer

Rosales-Reynoso

Saucedo-Sariñana

Contreras-Díaz

et al. 2019

Tohoku J. Exp. Med.

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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 G>T and rs459552 A>T), axis inhibition protein 1 (AXIN1) (rs9921222 C>T and rs1805105 C>T), AXIN2 (rs7224837 A>G), and dishevelled 2 (DVL2) (2074222 G>A and rs222836 C>T). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms in APC, DVL2, and AXIN1 Are Associated with Susceptibility, Advanced TNM Stage or Tumor Location in Colorectal Cancer

Rosales-Reynoso

Saucedo-Sariñana

Contreras-Díaz

et al. 2019

Tohoku J. Exp. Med.

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“…Also, a large number of studies have suggested that variants of Wnt signaling pathway genes contributed to cancer susceptibility. [18][19][20] Genetic variants of CTNNB1 could be used as indicators of gastric cancer risk and prognosis. 21 The APC polymorphism was a significant risk factor for colon cancer.…”

Section: Introductionmentioning

confidence: 99%

“…21 The APC polymorphism was a significant risk factor for colon cancer. 20 In recent years, some studies have verified that Wnt signaling attribute to cervical cancer pathology at multiple levels, including tumor proliferation, invasion, metastasis, angiogenesis, and therapeutic resistance. 22 Nevertheless, insufficient evidence suggests how various Wnt pathway genetic polymorphisms affect the risk of cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

Variations in the Wnt/β-Catenin Pathway Key Genes as Predictors of Cervical Cancer Susceptibility

Wang

et al. 2020

PGPM

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Background: Cervical cancer is the fourth most common and fatal tumor among women worldwide. The Wnt/β-catenin signaling pathway was etiologically involved in the cervical cancer model. Herein, we aimed to investigate whether germline genetic variations within the Wnt/β-catenin pathway can be genetic risk factors of cervical cancer. Patients and Methods: A total of 305 samples (147 patients, 158 controls) were included. Eight genetic variations located in APC (rs454886), GSK3β (rs3755557), CTNNB1 (rs11564475, rs1798802, rs3864004, rs2293303, and rs4135385), and TCF7L2 (rs7903146) were genotyped via Sanger sequencing. The χ 2 test and non-conditional logistic regression were used in the singlelocus analysis. Gene-gene interactions and haplotype construction in case-control samples were performed by the GMDR method and Haploview software, respectively. Results: The frequency of CTNNB1 rs1798802 GA+AA genotype was significantly lower in cervical cancer patients adjusted for age (OR=0.626, 95% CI=0.398-0.984). The mutant alleles of rs3864004 (A) and rs2293303 (T) located in CTNNB1 showed 1.513 (1.038-2.207), and 1.654 (1.020-2.683) fold increased risk of cervical cancer, respectively. Haplotype analysis showed no association between haplotypes of the CTNNB1 gene and cervical cancer risk. No significant contribution of interactions among genes in the Wnt pathway was identified. Conclusion: We concluded that the genetic variants in the CTNNB1 gene might contribute to the development of cervical cancer.

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“…SNPs are single base changes in a DNA sequence. Germ-line differences in DKK3 SNPs between cancerous and normal cases have been identified (9,(49)(50)(51)(52)(53)(54)(55)(56). The effects of DKK3 SNPs on disease susceptibility have been investigated in several cancers.…”

Section: Single Nucleotide Polymorphisms (Snps) In Dkk3mentioning

confidence: 99%

Dickkopf-3 in Human Malignant Tumours: A Clinical Viewpoint

2020

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Genetic variants in the WNT signaling pathway are protectively associated with colorectal cancer in a Saudi population

Cited by 11 publications

References 16 publications

Genetic Polymorphisms in <i>APC, DVL2</i>, and <i>AXIN1 </i>Are Associated with Susceptibility, Advanced TNM Stage or Tumor Location in Colorectal Cancer

Genetic Polymorphisms in <i>APC, DVL2</i>, and <i>AXIN1 </i>Are Associated with Susceptibility, Advanced TNM Stage or Tumor Location in Colorectal Cancer

<p>Variations in the Wnt/β-Catenin Pathway Key Genes as Predictors of Cervical Cancer Susceptibility</p>

Dickkopf-3 in Human Malignant Tumours: A Clinical Viewpoint

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