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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 study flow chart of case recruitment to screenH. pyloriinfection. In total, 389 family relatives (GCF) from 195 non-cardiac gastric cancer (GCA) index patients, including different familial relations, were enrolled. Blood sampling for DNA extraction and H. pylori screening with the urea breath test (UBT) were performed in all 389 GCF. There were also 143 of 173 duodenal ulcer patients to receive blood sampling and H. pylori screening. The differences in single nucleotide polymorphisms (SNPs) were compared between the DNA of 195 GCA children and 143 duodenal ulcer controls. Of the 88 H. pylori-infected children of GCA, 56 received endoscopy and topographical biopsies to assess whether the corpus predominant gastritis index (CGI), atrophy (AT), spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia (IM) correlated to the SNPs of ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 identified from the comparison between the children of GCA and the duodenal ulcer controls.
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Fig1: The study flow chart of case recruitment to screenH. pyloriinfection. In total, 389 family relatives (GCF) from 195 non-cardiac gastric cancer (GCA) index patients, including different familial relations, were enrolled. Blood sampling for DNA extraction and H. pylori screening with the urea breath test (UBT) were performed in all 389 GCF. There were also 143 of 173 duodenal ulcer patients to receive blood sampling and H. pylori screening. The differences in single nucleotide polymorphisms (SNPs) were compared between the DNA of 195 GCA children and 143 duodenal ulcer controls. Of the 88 H. pylori-infected children of GCA, 56 received endoscopy and topographical biopsies to assess whether the corpus predominant gastritis index (CGI), atrophy (AT), spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia (IM) correlated to the SNPs of ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 identified from the comparison between the children of GCA and the duodenal ulcer controls.

Mentions: This study prospectively and consequently enrolled 389 family relatives of 193 non-cardiac gastric adenocarcinoma (GCA) index patients and 173 benign DU, all of whom joined a screening project for H. pylori infection (NHRI-EX101-9908 BI). A number of the subjects have been referred from the recently published study by our group [12], and the emerging increase of the additional subjects were collected from the funding of the same multi-component grant to fulfill the statistical power required to answer the question whether or not any host genomic predisposition in several candidate genes can exist in the high-risk gastric cancer relatives different to low-risk gastric cancer patients, and to correlate with the presence of precancerous lesions with an increased risk of gastric cancer, especially after H. pylori infection. All of the enrolled study subjects provided written informed consent before entering the study. Both the consent form and study design were reviewed by the Research Ethics Committee of National Cheng Kung University Hospital (certification code: HR-98-023). A flow chart of patient enrollment and the familial relationships to the GCA index patients are shown in Figure 1. Among the 389 GCF, there were 61 spouses, 43 siblings, 205 children, 49 grandchildren and 31 other relatives. Each of the enrolled subjects provided blood samples to collect DNA.Figure 1


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 study flow chart of case recruitment to screenH. pyloriinfection. In total, 389 family relatives (GCF) from 195 non-cardiac gastric cancer (GCA) index patients, including different familial relations, were enrolled. Blood sampling for DNA extraction and H. pylori screening with the urea breath test (UBT) were performed in all 389 GCF. There were also 143 of 173 duodenal ulcer patients to receive blood sampling and H. pylori screening. The differences in single nucleotide polymorphisms (SNPs) were compared between the DNA of 195 GCA children and 143 duodenal ulcer controls. Of the 88 H. pylori-infected children of GCA, 56 received endoscopy and topographical biopsies to assess whether the corpus predominant gastritis index (CGI), atrophy (AT), spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia (IM) correlated to the SNPs of ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 identified from the comparison between the children of GCA and the duodenal ulcer controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: The study flow chart of case recruitment to screenH. pyloriinfection. In total, 389 family relatives (GCF) from 195 non-cardiac gastric cancer (GCA) index patients, including different familial relations, were enrolled. Blood sampling for DNA extraction and H. pylori screening with the urea breath test (UBT) were performed in all 389 GCF. There were also 143 of 173 duodenal ulcer patients to receive blood sampling and H. pylori screening. The differences in single nucleotide polymorphisms (SNPs) were compared between the DNA of 195 GCA children and 143 duodenal ulcer controls. Of the 88 H. pylori-infected children of GCA, 56 received endoscopy and topographical biopsies to assess whether the corpus predominant gastritis index (CGI), atrophy (AT), spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia (IM) correlated to the SNPs of ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 identified from the comparison between the children of GCA and the duodenal ulcer controls.
Mentions: This study prospectively and consequently enrolled 389 family relatives of 193 non-cardiac gastric adenocarcinoma (GCA) index patients and 173 benign DU, all of whom joined a screening project for H. pylori infection (NHRI-EX101-9908 BI). A number of the subjects have been referred from the recently published study by our group [12], and the emerging increase of the additional subjects were collected from the funding of the same multi-component grant to fulfill the statistical power required to answer the question whether or not any host genomic predisposition in several candidate genes can exist in the high-risk gastric cancer relatives different to low-risk gastric cancer patients, and to correlate with the presence of precancerous lesions with an increased risk of gastric cancer, especially after H. pylori infection. All of the enrolled study subjects provided written informed consent before entering the study. Both the consent form and study design were reviewed by the Research Ethics Committee of National Cheng Kung University Hospital (certification code: HR-98-023). A flow chart of patient enrollment and the familial relationships to the GCA index patients are shown in Figure 1. Among the 389 GCF, there were 61 spouses, 43 siblings, 205 children, 49 grandchildren and 31 other relatives. Each of the enrolled subjects provided blood samples to collect DNA.Figure 1

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