Genome-wide identification of m6a-associated single-nucleotide polymorphisms in colorectal cancer

Abstract

Background: N6-methyladenosine (m6A)-associated single-nucleotide polymorphisms (SNPs) play important roles in cancers, with previous research suggesting potential associa-tions 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 genomewide 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 CRCassociated 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.