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

Chu CM, Chen CJ, Chan DC, Wu HS, Liu YC, Shen CY, Chang TM, Yu JC, Harn HJ, Yu CP, Yang MH - World J Surg Oncol (2014)

Bottom Line: The genotypic polymorphisms in the -160 promoter region, exons and intron-exon boundaries of CDH1 were detected by direct sequencing analysis.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.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No, 325, Sec, 2, Cheng-Kung Road, Neihu, Taipei 11490, Taiwan. dlyaochi@gmail.com.

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

Immunohistochemical staining for E-cadherin. (a) E-cadherin-positive (++) in intestinal type cancer. (b) E-cadherin-negative (−) in diffuse type cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4230630&req=5

Figure 1: Immunohistochemical staining for E-cadherin. (a) E-cadherin-positive (++) in intestinal type cancer. (b) E-cadherin-negative (−) in diffuse type cancer.

Mentions: The 134 controls were composed of 86 males and 48 females. Their mean age was 51.06 ± 13.04 years (range = 19 to 89 years). The 167 gastric cancer cases comprised 114 males and 53 females. Their mean age was 69.11 ± 13.04 years (range = 27 to 90 years). According to Laurén’s classification system, 107 cases were of the diffuse type and 60 cases were of the intestinal type. The mean age of the diffuse type cases was 66.87 ± 13.81 years (range = 27 to 90 years) and that of the intestinal type cases was 73.82 ± 9.76 years (range = 48 to 88 years). The mean age of the diffuse type cases was approximately 7 years younger than that of the intestinal type cases. No differences were observed with respect to gender or TNM stages I to III in these two types. There were significantly more diffuse gastric cancer cases classified as stage IV. Reduced E-cadherin expression (Figure 1) was more frequent in the diffuse type cases than in the intestinal type cases. Comparison of the characteristics between these two case types is summarized in Table 1.


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

Chu CM, Chen CJ, Chan DC, Wu HS, Liu YC, Shen CY, Chang TM, Yu JC, Harn HJ, Yu CP, Yang MH - World J Surg Oncol (2014)

Immunohistochemical staining for E-cadherin. (a) E-cadherin-positive (++) in intestinal type cancer. (b) E-cadherin-negative (−) in diffuse type cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230630&req=5

Figure 1: Immunohistochemical staining for E-cadherin. (a) E-cadherin-positive (++) in intestinal type cancer. (b) E-cadherin-negative (−) in diffuse type cancer.
Mentions: The 134 controls were composed of 86 males and 48 females. Their mean age was 51.06 ± 13.04 years (range = 19 to 89 years). The 167 gastric cancer cases comprised 114 males and 53 females. Their mean age was 69.11 ± 13.04 years (range = 27 to 90 years). According to Laurén’s classification system, 107 cases were of the diffuse type and 60 cases were of the intestinal type. The mean age of the diffuse type cases was 66.87 ± 13.81 years (range = 27 to 90 years) and that of the intestinal type cases was 73.82 ± 9.76 years (range = 48 to 88 years). The mean age of the diffuse type cases was approximately 7 years younger than that of the intestinal type cases. No differences were observed with respect to gender or TNM stages I to III in these two types. There were significantly more diffuse gastric cancer cases classified as stage IV. Reduced E-cadherin expression (Figure 1) was more frequent in the diffuse type cases than in the intestinal type cases. Comparison of the characteristics between these two case types is summarized in Table 1.

Bottom Line: The genotypic polymorphisms in the -160 promoter region, exons and intron-exon boundaries of CDH1 were detected by direct sequencing analysis.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.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No, 325, Sec, 2, Cheng-Kung Road, Neihu, Taipei 11490, Taiwan. dlyaochi@gmail.com.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus