Huitong Chen1, Yong Li2, Li Li3, Jinhong Zhu1,4, Zhonghua Yang5, Jiao Zhang6, Suhong Li7, Yijuan Xin8, Huimin Xia1, Jing He1. 1. Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China. 2. Department of Pediatric Surgery, Hunan Children's Hospital, Changsha, Hunan, China. 3. Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Institute of Pediatrics Research, Yunnan Medical Center for Pediatric Diseases, Kunming Children's Hospital, Kunming, Yunnan, China. 4. Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. 5. Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. 6. Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 7. Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan, Shannxi, China. 8. Clinical Laboratory Medicine Center of PLA, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
Abstract
BACKGROUND: Hepatoblastoma is a commonly occurring embryonal tumors in children. N6-methyladenosine (m6 A) plays a critical role in gene expression, thus contributing to the occurrence and progression of cancer. RNA splicing is regulated by the nuclear m6 A reader YTHDC1, yet the roles of YTHDC1 polymorphisms in hepatoblastoma remain unclear. METHODS: We conducted a seven-center case-control study to determine the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C and rs3813832 T>C) and hepatoblastoma susceptibility. We recruited 313 hepatoblastoma patients and 1446 healthy controls. RESULTS: There was no significant association between all of these polymorphisms and hepatoblastoma susceptibility in single locus or combined analysis. Stratification analysis revealed that rs2293596 TC/CC genotype carriers had a higher risk of developing hepatoblastoma in the subgroup of clinical stages III + IV [adjusted odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.18-2.76, p = 0.007]. In addition, 3 risk genotype carriers are more likely to develop hepatoblastoma in the subgroup of clinical stages III + IV (adjusted OR = 1.80, 95% CI = 1.18-2.76, p = 0.007). Furthermore, false-positive probability analysis was used to notarize our findings. Haplotype analysis indicated that there was no significant association between inferred haplotypes of YTHDC1 gene based on observed genotypes and hepatoblastoma risk. CONCLUSIONS: In conclusion, our findings suggest that the rs2293596 T>C polymorphism may contribute to hepatoblastoma susceptibly and YTHDC1 gene polymorphisms may have a cumulative effect on hepatoblastoma risk.
BACKGROUND:Hepatoblastoma is a commonly occurring embryonal tumors in children. N6-methyladenosine (m6 A) plays a critical role in gene expression, thus contributing to the occurrence and progression of cancer. RNA splicing is regulated by the nuclear m6 A reader YTHDC1, yet the roles of YTHDC1 polymorphisms in hepatoblastoma remain unclear. METHODS: We conducted a seven-center case-control study to determine the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C and rs3813832 T>C) and hepatoblastoma susceptibility. We recruited 313 hepatoblastomapatients and 1446 healthy controls. RESULTS: There was no significant association between all of these polymorphisms and hepatoblastoma susceptibility in single locus or combined analysis. Stratification analysis revealed that rs2293596 TC/CC genotype carriers had a higher risk of developing hepatoblastoma in the subgroup of clinical stages III + IV [adjusted odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.18-2.76, p = 0.007]. In addition, 3 risk genotype carriers are more likely to develop hepatoblastoma in the subgroup of clinical stages III + IV (adjusted OR = 1.80, 95% CI = 1.18-2.76, p = 0.007). Furthermore, false-positive probability analysis was used to notarize our findings. Haplotype analysis indicated that there was no significant association between inferred haplotypes of YTHDC1 gene based on observed genotypes and hepatoblastoma risk. CONCLUSIONS: In conclusion, our findings suggest that the rs2293596 T>C polymorphism may contribute to hepatoblastoma susceptibly and YTHDC1 gene polymorphisms may have a cumulative effect on hepatoblastoma risk.
Authors: Zhaolin Chen; Ying Hu; Le Jin; Fan Yang; Haiwen Ding; Lei Zhang; Lili Li; Tingting Pan Journal: Front Pharmacol Date: 2022-04-06 Impact factor: 5.988