AXIN2 polymorphism and its association with prostate cancer in a Turkish population

Abstract

Polymorphism of AXIN2, a component of Wnt signaling, has been shown to play a role in tumorigenesis and dysregulated in cancer cells. In order to find out if AXIN2 polymorphism is a risk factor for prostate cancer, we analyzed eight polymorphic regions of this gene in 84 patients with prostate cancer and compared the results with 100 healthy controls in a Turkish population using PCR-RFLP methods. The genotype frequencies and risk factors of prostate cancer and control groups were analyzed by Chi-square test. We found a statistically significant result between prostate cancer risk and AXIN2 Intron2-956+16A/G (rs35285779) SNP. The frequency of the homozygous G/G (0%) and heterozygous A/G (18%) genotypes was significantly less in patients with prostate cancer than in healthy controls (7 and 32%, respectively) (P<0.05) for this SNP. When compared with the wild-type A/A genotype of the controls, prostate cancer patients with the A/G and G/G genotype showed reduced risk of cancer; the adjusted odds ratio (OR) for patients with the homozygous G/G genotype was 0.87 (95% CI: 0.81-0.95) and for heterozygous A/G genotype was 0.42 (95% CI: 0.20-0.85). We found no statistically significant association between controls and prostate cancer for other seven SNPs of AXIN2 including Exon1-148 C/T (rs2240308), Exon1-432 T/C (rs2240308), Exon5-1365 G/A (rs9915936), Exon5-1386 C/T (rs1133683), Intron5-1712+19 T/G, Exon7-2062 C/T, and Intron7-2141+73 G/A (rs4072245) (P>0.05). These results suggest that the AXIN2 Intron2 rs35285779 SNP is associated with development of prostate cancer as a protective SNP, while an association between other seven SNPs of the AXIN2 and risk of prostate cancer was not observed.

AXIN2 Polymorphisms, the β-Catenin Destruction Complex Expression Profile and Breast Cancer Susceptibility

“…Prior studies evaluated the association between rs2240308 polymorphism and cancer, tooth agenesis and orofacial clefts risk. Some reports did not find association between this polymorphism and orofacial clefts, prostate, ovarian, head and neck cancer (Kanzaki et al, 2006;Letra et al, 2009;Pinarbasi et al, 2011;Mostowska et al, 2014). However, Gunnes et al and Kanzaki et al evaluated the rs2240308 SNP in Turkish and Japanese populations, respectively, and its association with lung cancer (Kanzaki et al, 2006;Gunes et al, 2009 DOI:http://dx.doi.org/10.7314/APJCP.2015.16.16.7277 Axin2 Polymorphisms, the β-Catenin Destruction Complex Expression Profile and Breast Cancer Susceptibility PBMCs of breast cancer patients from North-America (Wang et al, 2008), but the authors did not find association between rs2240308 polymorphism and breast cancer risk.…”

Significant association between the Axin2 rs2240308 single nucleotide polymorphism and the incidence of prostate cancer

“…Alterations in the Axin2 gene have been detected in several cancer types (13). Certain mutations of the Axin gene are found in the functional domains, including the β-catenin and APC binding sites, and sequence variants have been reported in colon and ovarian cancer (20).…”

“…The mutation of the Axin2 gene and the loss of heterozygosity in the genomic locus have been observed in certain cancers, including colorectal, hepatocellular and ovarian cancer (13). It appears that the function of the Axin2 gene as a negative regulator of Wnt signaling is closely associated with the degradation of β-catenin, and in this way, affects carcinogenesis (9,10).…”

“…It appears that the function of the Axin2 gene as a negative regulator of Wnt signaling is closely associated with the degradation of β-catenin, and in this way, affects carcinogenesis (9,10). Several types of single nucleotide polymorphisms (SNPs) have been reported in the Axin2 coding region, including rs2240308 (exon1), rs9915936 (exon5) and rs1133683 (exon5) (13). Among these Axin2 SNPs, a significant association between rs2240308 [guanine (G)/adenine (A); also described as 148 cytosine (C)/thymine (T), or CCT/TCT (Proline (Pro)/Serine (Ser)), or Pro50Ser] and the risk of lung cancer has been reported previously (14,15).…”

Relationship between multidrug resistance 1 polymorphisms and the risk of prostate cancer in Chinese populations

“…The pathogenesis of Pca is still largely unknown, with genetic and environmental factors likely contributing to increased risk of the disease (Pienta and Esper 1993;Lichtenstein et al, 2000;Schaid, 2004). Several candidate genes have been suggested to be associated with Pca, including multidrug resistance 1 (MDR1) (van Brussel and Mickisch, 2003;Sanchez et al, 2009;Sanchez et al, 2011), X-ray repair complementing group 1 (Hirata et al, 2007;Agalliu et al, 2010;Dhillon et al, 2011;Kuasne et al, 2011;Langsenlehner et al, 2011), xeroderma pigmentosum group D gene (Mandal et al, 2010), APEX nuclease 1 gene (Agalliu et al, 2010;Kuasne et al, 2011;Mittal et al, 2012), Toll-like receptor 4 (Jing et al, 2012), axis inhibition protein 2 (Pinarbasi et al, 2011), 2-5A-dependent RNase (Wei et al, 2012), complementation group G gene (Berhane et al, 2012), and N-acetyltransferase types 1 (Gong et al, 2011) and 2 (Gong et al, 2011;de Lima Junior et al, 2012). MDR1 is an important candidate gene for Pca.…”