Frequent polymorphism of peroxisome proliferator activated receptor gamma gene in colorectal cancer containing wild-type K-ras gene.

We analyzed the K-ras gene mutation and the polymorphism of peroxisome proliferator activated receptor gamma (PPARgamma) gene, which is known as a master gene for adipocyte differentiation and a tumor suppressor gene, in patients with colorectal cancer by polymerase chain reaction-restriction fragment length polymorphism. We detected a mutation of K-ras gene at codon 12 in 8 of 39 colorectal cancers. We also detected a polymorphism of PPARgamma gene at codon 12 in 10 of 39 patients with colorectal cancer. Homozygous polymorphism (Ala12Ala) in PPARgamma gene was found only in one patient, but heterozygous polymorphism (Pro12Ala) was found in 9 of 29 patients. Surprisingly, all 10 colorectal cancers developed in the patients with polymorphism of PPARgamma gene carrying the wild-type K-ras gene. These findings suggest that PPARgamma gene polymorphism may be implicated with the development of colorectal cancers, in which K-ras gene is not mutated.