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Genomic single nucleotide polymorphisms in the offspring of gastric cancer patients predispose to spasmolytic polypeptide-expressing metaplasia after H. pylori infection.

Tsai YC, Hsiao WH, Lin SH, Yang HB, Cheng HC, Chang WL, Lu CC, Sheu BS - J. Biomed. Sci. (2015)

Bottom Line: The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU.The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10(-4)), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016).Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10(-4)).

View Article: PubMed Central - PubMed

Affiliation: Departments of Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. dr.aching@msa.hinet.net.

ABSTRACT

Background: Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM).

Results: There were 389 family relatives of 193 non-cardiac GCA and 173 duodenal ulcer patients (DU), received blood sampling for DNA collection. The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU. The children of GCA had higher allele frequencies of ITGA5-1160 T-carrier (P = 0.006, OR[95% CI] = 2.2[1.2-4]), ITGB1-1949 A-carrier (P = 0.047; OR[95% CI] = 2.8[1.4-5.3]), ITGB1 + 31804 C-carrier (P = 0.013; OR[95% CI] = 4.7[1.7-13.0]), IL-10-592 AA (P = 0.014; OR[95% CI] = 2.3[1.4-4.0]) and COX-2-1195 G-carrier (P = 0.019; OR[95% CI] = 1.7[0.9-3.2]) than DU. The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10(-4)), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016). Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10(-4)).

Conclusions: The SNPs of ITGA5-1160/ITGB1-1949/ ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA, or more specific to combine RUNX3 + 492/TFF2-308 as A-carrier/CC shall be host factor predisposing to gastric cancer during H. pylori infection, and serve as marker to identify high-risk subjects for H. pylori eradication.

No MeSH data available.


Related in: MedlinePlus

The combined risk genotypes’ distribution in gastric cancer familial relatives. A. The prevalences of the ITGA5-1160/ ITGB1-1949/ITGB1 + 31804 as T-carrier/A-carrier/C-carrier and COX-2-1195/IL10-592 as G-carrier/AA among different GCA familial relative groups were shown. The children of gastric cancer patients had higher prevalence of the presence of either or both risk combination SNPs in ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA than other familial relative groups (P = 0.018). B. There were no difference in the combined genotype of RUNX3 + 492/TFF2-308 as A-carrier/cm3 among different familial groups of gastric cancer patients (P = 0.313).
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Fig2: The combined risk genotypes’ distribution in gastric cancer familial relatives. A. The prevalences of the ITGA5-1160/ ITGB1-1949/ITGB1 + 31804 as T-carrier/A-carrier/C-carrier and COX-2-1195/IL10-592 as G-carrier/AA among different GCA familial relative groups were shown. The children of gastric cancer patients had higher prevalence of the presence of either or both risk combination SNPs in ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA than other familial relative groups (P = 0.018). B. There were no difference in the combined genotype of RUNX3 + 492/TFF2-308 as A-carrier/cm3 among different familial groups of gastric cancer patients (P = 0.313).

Mentions: We further assessed whether the different gastric cancer familial relative groups had different proportions of the combined SNPs predisposing to SPEM. In Figure 2A, the offspring, including children and grandchildren, of GCA had a higher rate of ITGA5-1160/ITGB1-1949/ITGB1 + 31804/COX-2-1195/IL-10-592 as T-carrier/A-carrier/C-carrier/G-carriers/AA than other familial groups (P = 0.018). However, in Figure 2B, there was no difference in the combined genotype of RUNX3 + 492/TFF2-308 as A-carrier/CC among the different familial groups of GCA (P = 0.313). Furthermore, children of the GCA index patients carrying the combination sets of ITGA5-1160/ITGB1-1949/ITGB1 + 31804/COX-2-1195/IL-10-592 as T-carrier/A-carrier/C-carrier/G-carriers/AA also had a higher prevalence of the same combination SNPs than children of GCA index patients not carrying such combinations of SNPs (43% vs. 16%; P = 0.003; OR 3.9; 95% CI: 1.6-9.6).Figure 2


Genomic single nucleotide polymorphisms in the offspring of gastric cancer patients predispose to spasmolytic polypeptide-expressing metaplasia after H. pylori infection.

Tsai YC, Hsiao WH, Lin SH, Yang HB, Cheng HC, Chang WL, Lu CC, Sheu BS - J. Biomed. Sci. (2015)

The combined risk genotypes’ distribution in gastric cancer familial relatives. A. The prevalences of the ITGA5-1160/ ITGB1-1949/ITGB1 + 31804 as T-carrier/A-carrier/C-carrier and COX-2-1195/IL10-592 as G-carrier/AA among different GCA familial relative groups were shown. The children of gastric cancer patients had higher prevalence of the presence of either or both risk combination SNPs in ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA than other familial relative groups (P = 0.018). B. There were no difference in the combined genotype of RUNX3 + 492/TFF2-308 as A-carrier/cm3 among different familial groups of gastric cancer patients (P = 0.313).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4340867&req=5

Fig2: The combined risk genotypes’ distribution in gastric cancer familial relatives. A. The prevalences of the ITGA5-1160/ ITGB1-1949/ITGB1 + 31804 as T-carrier/A-carrier/C-carrier and COX-2-1195/IL10-592 as G-carrier/AA among different GCA familial relative groups were shown. The children of gastric cancer patients had higher prevalence of the presence of either or both risk combination SNPs in ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA than other familial relative groups (P = 0.018). B. There were no difference in the combined genotype of RUNX3 + 492/TFF2-308 as A-carrier/cm3 among different familial groups of gastric cancer patients (P = 0.313).
Mentions: We further assessed whether the different gastric cancer familial relative groups had different proportions of the combined SNPs predisposing to SPEM. In Figure 2A, the offspring, including children and grandchildren, of GCA had a higher rate of ITGA5-1160/ITGB1-1949/ITGB1 + 31804/COX-2-1195/IL-10-592 as T-carrier/A-carrier/C-carrier/G-carriers/AA than other familial groups (P = 0.018). However, in Figure 2B, there was no difference in the combined genotype of RUNX3 + 492/TFF2-308 as A-carrier/CC among the different familial groups of GCA (P = 0.313). Furthermore, children of the GCA index patients carrying the combination sets of ITGA5-1160/ITGB1-1949/ITGB1 + 31804/COX-2-1195/IL-10-592 as T-carrier/A-carrier/C-carrier/G-carriers/AA also had a higher prevalence of the same combination SNPs than children of GCA index patients not carrying such combinations of SNPs (43% vs. 16%; P = 0.003; OR 3.9; 95% CI: 1.6-9.6).Figure 2

Bottom Line: The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU.The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10(-4)), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016).Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10(-4)).

View Article: PubMed Central - PubMed

Affiliation: Departments of Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. dr.aching@msa.hinet.net.

ABSTRACT

Background: Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM).

Results: There were 389 family relatives of 193 non-cardiac GCA and 173 duodenal ulcer patients (DU), received blood sampling for DNA collection. The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU. The children of GCA had higher allele frequencies of ITGA5-1160 T-carrier (P = 0.006, OR[95% CI] = 2.2[1.2-4]), ITGB1-1949 A-carrier (P = 0.047; OR[95% CI] = 2.8[1.4-5.3]), ITGB1 + 31804 C-carrier (P = 0.013; OR[95% CI] = 4.7[1.7-13.0]), IL-10-592 AA (P = 0.014; OR[95% CI] = 2.3[1.4-4.0]) and COX-2-1195 G-carrier (P = 0.019; OR[95% CI] = 1.7[0.9-3.2]) than DU. The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10(-4)), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016). Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10(-4)).

Conclusions: The SNPs of ITGA5-1160/ITGB1-1949/ ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA, or more specific to combine RUNX3 + 492/TFF2-308 as A-carrier/CC shall be host factor predisposing to gastric cancer during H. pylori infection, and serve as marker to identify high-risk subjects for H. pylori eradication.

No MeSH data available.


Related in: MedlinePlus