Variations in AXIN2 predict risk and prognosis of colorectal cancer

Abstract

Objective Colorectal cancer (CRC) and hypodontia are frequent and different diseases with common genes are involved in their etiology. The objective of this study was to identify the association between AXIN2 rs2240308 with hypodontia and CRC. Patients and methods This study consisted of 50 individuals with hypodontia, 50 individuals with CRC, and 155 healthy individuals from Colombia. SNP genotyping assays of rs2240308 were performed and family history of cancer in individuals with hypodontia was documented. In silico analysis was implemented to define the genomic profile of the AXIN2 gene associated with CRC. Multivariate analysis, chi square, odd ratio tests, and R software were used for statistical analysis. Results AXIN2 rs2240308 showed association with CRC (OR = 5.4 CI: 2.7–10.4; p < 0.001) and with other familial cancer in individuals with hypodontia (p < 0.005 OR = 1.75, 95% CI: 1.22–6.91). In silico analysis showed that variations in AXIN2 found in CRC patients, were more frequently in earlier stages of tumor and patients who carry variations in the AXIN2 gene have a worse prognosis (p < 0.05). The association between AXIN2 rs2240308 with hypodontia was not significant. Conclusions These results suggest that AXIN2 rs2240308 polymorphism is associated with CRC and AXIN2 could be a risk marker for predisposition and prognosis of CRC.

Tooth agenesis: What do we know and is there a connection to cancer?

“…A genotyping study of AXIN2 rs2240308 polymorphism in 50 patients with CRC, 50 hypodontia patients and 155 healthy individuals revealed no significant relationship between this SNP and simultaneous occurrence of hypodontia and CRC. However, results suggest that AXIN2 rs2240308 polymorphism is associated with CRC 69 . Küchler et al 51 added to AXIN2 rs2240308 and rs740026 another 12 polymorphisms in FGF3 , FGF10 , and FGFR2 and all markers were genotyped in 82 individuals with tooth agenesis and 328 individuals with no defect of dentition.…”

Significant Associations between AXIN1 rs1805105, rs12921862, rs370681 Haplotypes and Variant Genotypes of AXIN2 rs2240308 with Risk of Congenital Heart Defects

“…Previous studies evaluated the mentioned variant on patients with hypodontia and demonstrated that the presence of a variant allele was associated with frontal agenesis [29]. Also, the mentioned variant was previously associated with cancer risk, such as colorectal cancer [30], breast cancer [31], and Hirschsprung disease [32]. In the case of CHDs patients, other AXIN2 variants [c.28 C > T (p.L10F), c.395 A > G (p.K132R)] were previously reported by Zhu M et al [33] as pathogenic variants for CHDs.…”

Identification of Copy Number Variation Among Nonsyndromic Cleft Lip and or Without Cleft Palate With Hypodontia: A Genome-Wide Association Study

“…The variations in WNT genes have been recognized in an individual with tooth agenesis (Dinckan et al, 2016). Therefore, the AXIN2 mutations could lead to an inefficient block of the WNT signaling pathway and altered the embryonic development of dental organs and predisposition to cancer (Otero et al, 2019). We hypothesized that reduced induction of FHIT might be triggering AXIN2 mutation and directly producing WNT dysregulation in the progression of lip and palate fusion and tooth development and finally leading to abnormal growth.…”