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Background  Findings related to the influence of the −160C → A promoter polymorphism and haplotypes of the  E-cadherin  ( CDH1 ) gene have not been consistent in previous studies regarding the risk for sporadic gastric cancer. Investigators in most previous studies detected those genotypes using restriction fragment length polymorphism analysis. Therefore, we conducted a case–control study to investigate the association of the  CDH1  − 160C → A promoter polymorphism and haplotypes for cancer risk related to sporadic diffuse and intestinal gastric cancer by direct sequencing analysis.    Methods  We included 107 diffuse gastric cancer cases, 60 intestinal gastric cancer cases and 134 controls. The genotypic polymorphisms in the −160 promoter region, exons and intron–exon boundaries of  CDH1  were detected by direct sequencing analysis. Genotype frequencies were compared. The  CDH1  − 160C → A promoter polymorphism and four polymorphisms (48 + 6 T → C, 2076C → T, 2253C → T and 1937–13 T → C) were included in the haplotype analyses, which were estimated using the expectation–maximization algorithm.    Results  Compared to controls, the frequency of the −160A allele was significantly higher in diffuse gastric cancer cases ( P  = 0.005), but it was not significantly different in intestinal gastric cancer cases ( P  = 0.119). Two sets of three-marker haplotypes (−160C → A, 48 + 6 T → C, 2076C → T and −160C → A, 1937–13 T → C, 2253C → T) were associated with the risk of diffuse gastric cancer ( P  = 0.011 and  P  = 0.042, respectively).    Conclusion  Based on direct sequencing analysis, our findings suggest that the  CDH1  − 160C → A promoter polymorphism and haplotypes play significant roles in cancer risk for sporadic diffuse gastric cancer, but not for intestinal gastric cancer, in a Taiwanese population.

CDH1 polymorphisms and haplotypes in sporadic diffuse and intestinal gastric cancer: a case–control study based on direct sequencing analysis