TP53BP2 locus is associated with gastric cancer susceptibility

We investigated the association of the TP53BP2 locus with gastric cancer susceptibility in a Korean population. We assayed 9 single nucleotide polymorphisms (SNP) in an 82.5 kb region that included the TP53BP2 locus in 233 male gastric cancer patients and 390 unaffected healthy male controls. The allelic frequencies of 4 SNP within TP53BP2, g.206692C>T, g.198267A>T, g.164895G>A and g.152389A>T, differed significantly between cases and controls (p < or = 0.0376). When compared to carriers of non-risk alleles, individuals homozygotic for each of the risk alleles had a 50% increase in risk of gastric cancer (age-adjusted odds ratio [OR] > or = 1.48; p < or = 0.0371). Furthermore, these 4 significantly associated SNP were in strong linkage disequilibrium (r2 > or = 0.51). Haplotype analysis showed that individuals with the CAGA haplotype, consisting of the risk alleles at each SNP, had a 1.55-fold higher risk for gastric cancer than individuals with the haplotype TTAT, consisting of the non-risk alleles at each SNP (OR = 1.55; 95% confidence interval [CI] = 1.13-2.14; p = 0.00705). Two other SNP were not polymorphic in the study subjects, whereas the other 3 SNP, located toward the outside of the TP53BP2 locus, were not associated with gastric cancer susceptibility. Although the location of the pathogenic variant is not yet known, our results suggest that the TP53BP2 locus is associated with susceptibility to gastric cancer in the Korean population.