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OBJECTIVE To evaluate the p73 gene G4C14-to-A4T14 double nucleotide polvmorphism with both increased gastric cancer(GC)risk and different histological subtypes of GC in a northwest Chinese population.METHODS Genotyping of the polymorphism of the p73 gene was conducted with PCR-CTPP.RESULTS All 385 GC patients including 305 diffuse-type and 80 intestinal-type cases and 412 healthy controls were investigated.The frequencies of p73 AT/AT,AT/GC,and GC/GC KenotVpes were 28.1%,47.1%,and 24.8% in the controls,and were 22.0%,45.0%,and 33.0% in GC cases respectively;the GC/GC homozygote frequency was higher in GC cases,mainly in diffuse type compared to the controls with OR=1.71(1.16～2.51)and 1.87 (95% CI,1.24～2.81)respectively.The results showed that carriers of the p73 G4A GC/GC homozygote had a 1.71-time higher risk of GC,especially of the diffuse-tvpe GC compared to the controls.The carriers of the AT/GC heterozygote also had a slightly increased risk of GC cancer, mainly on intestinal-type GC This is the first report that the p73 G4A double-nucleotide polymorphism is associated with an increased risk of diffuse-type gastric cancer.CONCLUTION The p73 G4A GC/GC genotype is associated with an increased risk of gastric cancer,especially of the GC diffuse-type.