Background: 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