Genetic variants in p53 signaling pathway genes predict chemotherapy efficacy in colorectal cancer

Abstract

Background The murine double minute‐2 gene ( MDM2 ) was originally identified as predicting chemotherapy efficacy. However, little is known regarding the association between single nucleotide polymorphisms (SNPs) in the p53 signaling pathway and prognosis/chemotherapy sensitivity in colorectal cancer. Methods We analyzed the association between 111 SNPs in 22 p53 signaling pathway genes and both progression‐free survival (PFS) and disease control rate (DCR) using Cox regression and logistics regression analysis. The false discovery rate method was used for correction of multiple testing. Secondary structure was predicted by RNAfold. Expression qualitative trait locus analysis and mRNA expression differences were assessed using the GTEx and TCGA databases. Results We found that the rs747828 C allele of TP73 was significantly associated with reduced PFS (HR = 1.64, 95% CI = 1.27‐2.12, P = 2.00 × 10 −4 ) in the additive model. In the stratified analysis, the rs747828 C allele was significantly associated with both reduced PFS ( P = 1.40 × 10 −3 ) and DCR ( P = 1.82 × 10 −2 ) in oxaliplatin‐based chemotherapy. The secondary structure of TP73 was altered in response to different rs747828 genotypes. Although the rs747828 C allele was not associated with messenger RNA (mRNA) TP73 expression, it was significantly associated with increased mRNA TP73‐AS1 expression levels in sigmoid tissues. TP73 mRNA was significantly overexpressed in tumor tissues compared to adjacent normal tissues ( P = 2.36 × 10 −19 ). Conclusion Our findings indicate that functional genetic variants of TP73 mediate the response to chemotherapy in colorectal cancer.

RETRACTED: Long noncoding RNA TUG1 facilitates cell ovarian cancer progression through targeting MiR‐29b‐3p/MDM2 axis

“…It has been reported that MDM2 involves in a negative regulatory loop between p53 and MDM2. MDM2 plays as an oncogene through negatively regulating the expression and activation of p53 (Xu et al, 2019; Zhang et al, 2019). MDM2 is a primary regulator of p53, p53 is well known as a crucial tumor suppressor in cancer through initiating cell cycle arrest, cell apoptosis, and promotes cancer cell senescence (Ning et al, 2019).…”

Genetic variants in the Folic acid Metabolic Pathway Genes predict outcomes of metastatic Colorectal Cancer patients receiving first-line Chemotherapy

“…The protocol was approved by the Institutional Review Board of Nanjing Medical University. All patients gave their written informed consent before enrollment and the clinical characteristics of patients were described previously 14 .…”

Genetic variants in RNA m5C modification genes associated with survival and chemotherapy efficacy of colorectal cancer

“…Detailed information has been elucidated in our previous article. 20 Overall survival (OS) after chemotherapy was deemed the major endpoint in our analysis. It was calculated from the time of first chemotherapy to the time of last follow-up or death.…”