There is provided a method of determining a risk of gastrointestinal cancer in a human subject, the method comprising: determining in a biological sample of the subject, whether mutation is present in at least one CTCF-binding sites (CBS) overlapping regions, or portions or flanking sequences thereof, or at least one non-CBS regions, or portions or flanking sequences thereof, wherein presence of mutation in at least one CBS overlapping regions, or portions or flanking sequences thereof, and/or at least one non-CBS regions, or portions or flanking sequences thereof, is indicative of a risk of gastrointestinal cancer in the subject. There are also provided a method of treating gastrointestinal cancer in a human subject and related kits.