A novel TP53 variant (rs78378222 A > C) in the polyadenylation signal is associated with increased cancer susceptibility: evidence from a meta-analysis

// Ying Wang 1, * , Xue-Song Wu 2, * , Jing He 3, 4, * , Tianjiao Ma 5 , Wei Lei 1 , Zhen-Ya Shen 1 1 Department of Cardiovascular Surgery, The First Affiliated Hospital and Institute for Cardiovascular Science, Soochow University, Suzhou, Jiangsu, China 2 School of Humanities and Social Science, Harbin Medical University, Harbin, Heilongjiang, China 3 Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China 4 Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China 5 Department of Internal Medicine, Harbin Medical University, Harbin, Heilongjiang, China * These authors contributed equally to this work Correspondence to: Zhen-Ya Shen, email: uuzyshen@aliyun.com Keywords: TP53, rare variant, GWAS, apoptosis, polymorphism Received: March 01, 2016 Accepted: April 02, 2016 Published: April 27, 2016 ABSTRACT Polymorphisms in TP53 are involved in the progression of different types of cancer. A rare novel TP53 variant (rs78378222 A > C allele) was found via whole-genome sequencing in 2011. This variant was shown to significantly increase the risk of glioma, colorectal adenoma and prostate cancer. Functional analysis further revealed that this variant hindered TP53 expression and its downstream effect on apoptosis. Several studies have investigated the relationship between rs78378222 and cancer susceptibility. However, the results were not consistent. We conducted the first meta-analysis to give a more credible assessment on the association about this variant and cancer risk. Our meta-analysis included 34 studies consisting of 36599 cases and 91272 controls. These studies were mostly on the basis of high-grade data from Genome-wide association studies (GWASs). The results indicated that TP53 rs78378222 was significantly associated with an increased risk of overall cancer (AC vs. AA: OR = 1.511, 95% CI = 1.285–1.777). Furthermore, stratified analyses indicated that rs78378222 increased the risk of nervous system cancer, skin cancer and other cancer. To summarize, this meta-analysis suggested that rs78378222 C allele is a potent risk factor for overall cancer.