Pharmacogenomics and Personalized Medicine (Jul 2021)
Genome-Wide Identification of m6A-Associated Single-Nucleotide Polymorphisms in Colorectal Cancer
Abstract
Hongying Zhao,1 Jinying Jiang,1 Mingshan Wang,2 Zixue Xuan1,3 1Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Departments of Infection Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Mingshan Wang; Zixue Xuan Email [email protected]; [email protected]: N6-methyladenosine (m6A)-associated single-nucleotide polymorphisms (SNPs) play important roles in cancers, with previous research suggesting potential associations between m6A-SNPs and cancer. However, the relationship between the genetic determinants of m6A modification and colorectal cancer (CRC) remains unclear.Methods: An integrative method combining raw data and summary statistics of genome-wide association studies with expression quantitative trait loci (eQTL) and differential expression data was applied to screen potential candidate CRC-associated m6A-SNPs.Results: A total of 402 m6A-SNPs were identified as being associated with CRC (p < 0.001), with 98 showing eQTL signals. In particular, three genes were found to harbor CRC-associated m6A-SNPs: rs178184 in NOVA1, rs35782901 in HTR4, and rs60571683 in SLCO1B3. These genes were differentially expressed in at least one publicly available dataset (p < 0.05), with NOVA1 (p = 3.41× 10− 11) and HTR4 (p = 5.56× 10− 7) being significantly downregulated in CRC (dataset: GSE89076), and SLCO1B3 was significantly overexpressed (datasets: GSE32323 [p = 3.27× 10− 5], GSE21510 [p = 1.09× 10− 6], and GSE89076 [p = 7.63× 10− 6]).Conclusion: This study identified three m6A-SNPs (rs178184, rs35782901, and rs60571683) that may be associated with CRC. However, the lack of analysis of primary CRC samples in order to further elucidate the underlying pathogenesis is a major limitation of this study. Future investigations are needed to validate these CRC-associated m6A-SNPs and explore the m6A-mediated pathogenic mechanism in CRC.Keywords: colorectal cancer, genome-wide association study, N6-methyladenosine, single-nucleotide polymorphism
