J Cancer 2020; 11(17):5129-5134. doi:10.7150/jca.46120

Research Paper

YTHDF1 rs6090311 A>G polymorphism reduces Hepatoblastoma risk: Evidence from a seven-center case-control study

Zhendong Luo1#, Guoyuan Li1#, Mi Wang1#, Jinhong Zhu1,2, Zhonghua Yang3, Yong Li4, Jiao Zhang5, Yijuan Xin6, Suhong Li7, Li Li8, Zhenjian Zhuo1✉, 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 510623, Guangdong, China.
2. Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China.
3. Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
4. Department of Pediatric Surgery, Hunan Children's Hospital, Changsha 410004, Hunan, China.
5. Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
6. Clinical Laboratory Medicine Center of PLA, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China.
7. Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan 030013, Shannxi, China.
8. 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 650228, Yunnan, China.
#These authors contributed equally.

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Citation:
Luo Z, Li G, Wang M, Zhu J, Yang Z, Li Y, Zhang J, Xin Y, Li S, Li L, Zhuo Z, He J. YTHDF1 rs6090311 A>G polymorphism reduces Hepatoblastoma risk: Evidence from a seven-center case-control study. J Cancer 2020; 11(17):5129-5134. doi:10.7150/jca.46120. Available from https://www.jcancer.org/v11p5129.htm

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Abstract

Various factors modulate the risk of hepatoblastoma. In this study, we aimed to investigate whether single nucleotide polymorphisms (SNPs) in the YTHDF1 gene could predispose to hepatoblastoma. We used TaqMan assay to genotype two YTHDF1 SNPs (rs6011668 C>T and rs6090311 A>G) in a Chinese population composed of 313 subjects with hepatoblastoma and 1446 controls from seven hospitals. We then evaluated the associations of these two SNPs with hepatoblastoma risk using unconditional logistic regression. We found that rs6090311 G allele exhibited a significant association with decreased hepatoblastoma risk [AG vs. AA: adjusted odds ratio (OR)=0.75; 95% confidence interval (CI)=0.58-0.98, P=0.033; AG/GG vs. AA: adjusted OR=0.76, 95% CI=0.59-0.97, P=0.029]. Furthermore, the combined analysis of protective genotypes revealed that subjects carrying two protective genotypes were less likely to have hepatoblastoma than those with 0-1 protective genotypes (adjusted OR=0.75, 95% CI=0.59-0.96, P=0.022). Subjects ≥17 months of age had decreased hepatoblastoma risk, in case that they carried rs6090311 AG/GG (adjusted OR=0.63, 95% CI=0.44-0.91, P=0.012), or two protective genotypes (adjusted OR=0.63, 95% CI=0.44-0.91, P=0.012). False-positive report probability analysis validated the reliability of the significant results. Preliminary functional annotations revealed that rs6090311 G was correlated with decreased expression of its surrounding genes in the expression quantitative trait locus (eQTL) analysis. In conclusion, our results indicate that the rs6090311 A>G in the YTHDF1 gene is related to decreased hepatoblastoma risk.

Keywords: hepatoblastoma, risk, YTHDF1, polymorphism, case-control study