Genetic polymorphisms of Wnt/β-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma

Abstract

Radiotherapy (RT) is the normative therapeutic treatment for primary nasopharyngeal carcinoma (NPC). Single nucleotide polymorphisms (SNPs) of genes in Wnt/β-catenin pathway are correlated to the development, prognosis, and treatment benefit of various cancers. However, it has not been established whether SNPs of Wnt/β-catenin pathway are associated with nasopharyngeal tumorigenesis and the efficacy of RT in NPC patients. Therefore, in this study, we aimed to investigate the nine potentially functional SNPs of four genes in the Wnt/β-catenin pathway and genotyped these in 188 NPC patients treated with RT. To achieve this goal, associations between these SNPs and the RT's curative efficacy, as well as acute radiation-induced toxic reaction were determined by multifactorial logistic regression. We observed that catenin beta 1 gene (CTNNB1) rs1880481 and rs3864004, and glycogen synthase kinase 3 beta gene (GSK3β) rs3755557 polymorphisms were significantly associated with poorer efficacy of RT in NPC patients. Moreover, GSK3β rs375557 and adenomatous polyposis coli gene (APC) rs454886 polymorphisms were correlated with acute grade 3–4 radiation-induced dermatitis and oral mucositis, respectively. In conclusion, this study suggests that gene polymorphisms of Wnt/β-catenin may be novel prognostic factors for NPC patients treated with RT.

Polymorphisms and expression pattern of circular RNA circ-ITCH contributes to the carcinogenesis of hepatocellular carcinoma

“…Song et al [ 37 ] reported that Wnt/beta-catenin was also an oncogenic pathway targeted by H. pylori in gastric carcinogenesis. Genetic polymorphisms of Wnt/beta-catenin pathway genes are also associated with the susceptibility, survival, efficacy and toxicities of radiotherapy of multiple cancers [ 39 – 45 ]. In current study, we found the expression level of circ-ITCH in HCC tissues was significantly lower than the level in adjacent tissues, which indicated that circ-ITCH worked as an tumor suppressor gene for carcinogenesis of HCC, consistent with its function in ESCC, colorectal cancer, and lung cancer.…”

Polymorphism of regulatory region of GHRL gene (‐2531C>T) as a promising predictive factor for radiotherapy‐induced oral mucositis in patients with head neck cancer

“…The analysis of data from patients with head and neck cancer demonstrated a correlation between SNPs of genes: TGFB1 and XRCC1a (C allele of gene TGFB1 [T869C codon 10 Leu/Pro, rs1982073], A allele of the gene XRCC1 [G28152A, codon 399 Arg/Gln, rs25487]) and the intensity of late skin reactions. 8 The correlation was also confirmed between oral mucositis intensification, including dysphagia, and the healing process, [9][10][11][12] Intensification of dysphagia was also found in patients with one allelic variation of Wnt/b-catenin GSK3b (rs375557) gene and recessive variant of adenomatous polyposis coli gene (rs454886) polymorphisms. 13 The hypothesis of our study is that ghrelin is a potential factor modifying the cell nutrition status, local inflammatory process, and intensification of postirradiation reaction and that SNPs of the ghrelin coding gene (GHRL) are responsible for individual variability in oral mucositis intensification.…”

“…The analysis of data from patients with head and neck cancer demonstrated a correlation between SNPs of genes: TGFB1 and XRCC1a (C allele of gene TGFB1 [T869C codon 10 Leu/Pro, rs1982073], A allele of the gene XRCC1 [G28152A, codon 399 Arg/Gln, rs25487]) and the intensity of late skin reactions . The correlation was also confirmed between oral mucositis intensification, including dysphagia, and the healing process, and SNPs of DNA repair genes (eg, genotypes CT/TT [c.722] and CG/GG [Ku70c‐1310] of XRCC3 gene and allele C of the ERCC4 [T2505C] gene as well as SNPs of XRCC1 [c.1196A>G; allele A] and RAD51 [c.‐3429G>C] allele C genes) . Intensification of dysphagia was also found in patients with one allelic variation of Wnt/β‐catenin GSK3β (rs375557) gene and recessive variant of adenomatous polyposis coli gene (rs454886) polymorphisms …”

The relationship between TNF-α gene promoter polymorphism (− 1211 T > C), the plasma concentration of TNF-α, and risk of oral mucositis and shortening of overall survival in patients subjected to intensity-modulated radiation therapy due to head and neck cancer

“…To date, many studies were trying to evaluate the correlation between genetic variants and radiosensitivity and the reaction of normal tissues to irradiation. However, most of the studies assessing the association of SNPs with OM are focused on the following processes: DNA repair, oxidation and stress response, apoptosis [14], embryogenesis [27], as well as inflammation [14], and only one (our previous paper) concerned TNF-α -TNFR axis [28].…”