Midkine (MK) is a heparin-binding growth factor specified by a retinoic acid responsive gene. It plays important roles in development and carcinogenesis. The MK gene is located on chromosome 11q11.2 in humans. A heterozygous G to T transition at the 62nd base in intron 3 of this gene has been identified in sporadic colorectal and gastric cancers (Int. J. Mol. Med. 6 (2000) 281). To clarify whether this polymorphism is associated with a cancer risk, a case-control study was conducted. We examined 98 colorectal, 60 gastric, 59 esophagus, 32 lung and 37 breast cancer tissue specimens and their corresponding non-neoplastic tissues. Also, 86 unaffected control specimens were examined. The G/T genotype frequency in colorectal cancers was higher than that in normal samples (11.2 versus 2.3%; P=0.017). Therefore, this genotype could represent a risk factor for tumorigenesis in the colon and rectum of Japanese.