Mingyang Shen1, Lin Lin2. 1. Department of General surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China. 2. Department of General surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China. Electronic address: linlin_sy@aliyun.com.
Abstract
AIMS: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and accounts for substantial morbidity and mortality. Autophagy plays an essential role in the development and progression of HCC. This study aims to evaluate whether genetic variants in autophagy-related genes (ATGs) affect the development of HCC. MATERIALS AND METHODS: We conducted a case-control study with 986 HCC cases and 1000 healthy controls to analyze 14 functional variants of five ATGs (ATG3, ATG5, ATG10, ATG12 and ATG16L1) among a Chinese population. KEY FINDINGS: We found ATG5 rs17067724 (G vs A: OR = 0.80; 95% CI = 0.65-0.98; P = 0.031), ATG10 rs1864183 (G vs A: OR = 1.29; 95% CI = 1.07-1.57; P = 0.009), ATG10 rs10514231 (C vs T: OR = 1.41; 95% CI = 1.15-1.73; P = 0.001), ATG12 rs26537 (C vs T: OR = 1.16; 95% CI = 1.02-1.33; P = 0.030), and ATG16L1 rs4663402 (T vs A: OR = 1.28; 95% CI = 1.01-1.63; P = 0.044) were significantly associated with HCC risk. Specifically, ATG10 rs10514231 kept significant association even adjusted for Bonferroni correction (P = 0.001 × 14 = 0.014). Bioinformatics analyses showed that allele C of ATG10 rs10514231 was significantly correlated with higher expression of ATG10 gene in both HCC tissues and normal liver tissues. Dual-luciferase reporter assay presented that cell lines transfected with vectors containing the risk allele C of rs10514231 showed higher relative luciferase activity compared to that containing the allele T. SIGNIFICANCE: These results suggested that ATG10 rs10514231 might contribute to an allele-specific effect on the expression of host gene ATG10 and explain a fraction of HCC genetic susceptibility. Our study would benefit the construction of early warning model, early prevention, screening, even therapeutic target of HCC.
AIMS: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and accounts for substantial morbidity and mortality. Autophagy plays an essential role in the development and progression of HCC. This study aims to evaluate whether genetic variants in autophagy-related genes (ATGs) affect the development of HCC. MATERIALS AND METHODS: We conducted a case-control study with 986 HCC cases and 1000 healthy controls to analyze 14 functional variants of five ATGs (ATG3, ATG5, ATG10, ATG12 and ATG16L1) among a Chinese population. KEY FINDINGS: We found ATG5rs17067724 (G vs A: OR = 0.80; 95% CI = 0.65-0.98; P = 0.031), ATG10rs1864183 (G vs A: OR = 1.29; 95% CI = 1.07-1.57; P = 0.009), ATG10rs10514231 (C vs T: OR = 1.41; 95% CI = 1.15-1.73; P = 0.001), ATG12rs26537 (C vs T: OR = 1.16; 95% CI = 1.02-1.33; P = 0.030), and ATG16L1rs4663402 (T vs A: OR = 1.28; 95% CI = 1.01-1.63; P = 0.044) were significantly associated with HCC risk. Specifically, ATG10rs10514231 kept significant association even adjusted for Bonferroni correction (P = 0.001 × 14 = 0.014). Bioinformatics analyses showed that allele C of ATG10rs10514231 was significantly correlated with higher expression of ATG10 gene in both HCC tissues and normal liver tissues. Dual-luciferase reporter assay presented that cell lines transfected with vectors containing the risk allele C of rs10514231 showed higher relative luciferase activity compared to that containing the allele T. SIGNIFICANCE: These results suggested that ATG10rs10514231 might contribute to an allele-specific effect on the expression of host gene ATG10 and explain a fraction of HCC genetic susceptibility. Our study would benefit the construction of early warning model, early prevention, screening, even therapeutic target of HCC.
Authors: E Bueno-Martínez; M Lara-Almunia; C Rodríguez-Arias; A Otero-Rodríguez; S Garfias-Arjona; R González-Sarmiento Journal: BMC Cancer Date: 2022-02-05 Impact factor: 4.430