Tian J, Ying P, Ke J, et al. - Researchers examined 1,062 colorectal cancer (CRC) cases and 2,184 controls to inquire about the link of variants associated with N⁶-methyladenosine (m⁶A) modification with CRC risk, for the first time systematically, using exome-wide association data and followed by two replication sets comprising 7,341 CRC cases and 7,902 controls. They found a significant link of the variant rs8100241 located in ANKLE1 with CRC risk in 8,403 cases and 10,086 controls. Compared with rs8100241[G] allele overexpression, a significant rise in the ANKLE1 m⁶A level was induced by overexpression of the rs8100241[A] allele, which also facilitated the ANKLE1 protein expression. Mechanistically, the function of ANKLE1 as a potential tumor suppressor with tendency to inhibit cell proliferation and facilitate genomic stability was noted. ANKLE1 knockdown was associated with an elevated frequency of micronucleated cells, increased cell proliferation and colony formation ability. Overall, the ability of germline missense variant to increase CRC risk by impacting ANKLE1 m⁶A level was suggested in this study; this emphasizes that variants-associated m⁶A modification holds a clinical potential as a risk marker for CRC prevention.