Risk Of Gastric Cardiac Adenocarcinoma Research Articles

CDH1 Gene rs1801552 C/T Polymorphism Increases Susceptibility to Esophageal Squamous Cell Carcinoma but Not to Gastric Cardiac Adenocarcinoma

Purpose The present study aimed to investigate whether the single nucleotide polymorphism (SNP) rs1801552 C/T in CDH1 gene is correlated with the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), as a preliminary study. Methods The rs1801552 C/T polymorphism was genotyped by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 1316 cancer patients (810 ESCC and 506 GCA) and 1966 controls in north China. We performed two case–control studies, each of which included a population-based set and a hospital-based set. Results The data showed that the rs1801552 C/T polymorphism was associated with the risk of ESCC. Allelotype and genotype distributions of the rs1801552 C/T polymorphism in ESCC patients of high-incidence region and hospital were significantly different from that in their respective controls (p < 0.05). Compared with C/C genotype, T/T genotype increased the risk of ESCC in high-incidence region and hospital (age, sex, smoking status and family history of UGIC adjusted odds ratio (OR) = 1.79 and 2.10, 95% confidence interval (CI) = 1.23–2.60 and 1.10–4.04, respectively). Allelotype and genotype distributions of the rs1801552 C/T polymorphism in GCA patients were not significantly different from that in their controls, respectively (p > 0.05). Conclusions The findings in the present pilot study suggest that the rs1801552 C/T polymorphism was associated with the risk of ESCC, but was not associated with the risk of GCA in high-incidence region and hospital.

IL18 rs360719 A>G, IL18R1 rs13015714 G>T, IL18RAP rs917997 C>T and IL28B rs8099917 T>G polymorphisms and risk of gastric cardiac adenocarcinoma.

The present study was conducted to investigate the association between gastric cardiac adenocarcinoma (GCA) and four functional single-nucleotide polymorphisms (SNPs), including interleukin 18 (IL18) rs360719 A>G, IL18 receptor 1 (IL18R1) rs13015714 G>T, IL18 receptor accessory protein (IL18RAP) rs917997 C>T and interleukin 28B (IL28B) rs8099917 T>G variants. A hospital-based case-control study was performed to evaluate the genetic effects of these SNPs. A total of 243 GCA cases and 476 controls were enrolled in this study. A custom-by-design 48-Plex SNPscan™ kit was used to determine the genotypes. When the IL18 rs360719 AA homozygote genotype was used as the reference group, the AG genotype was not associated with the risk for GCA; the GG genotype was also not associated with the risk for GCA. In the dominant model, the IL18 rs360719 AG/GG variants were not associated with the risk for GCA, compared with the IL18 rs360719 AA genotype. In the recessive model, when the IL18R1 rs13015714 AA/AG genotypes were used as the reference group, the GG homozygote genotype was not associated with risk for GCA. No association was observed between IL18R1 rs13015714 G>T, IL18RAP rs917997 C>T and IL28B rs8099917 T>G polymorphisms and the risk for GCA. These results demonstrated that the functional polymorphisms IL18 rs360719 A>G, IL18R1 rs13015714 G>T, IL18RAP rs917997 C>T and IL28B rs8099917 T>G do not contribute to GCA susceptibility. However, as the statistical power of our study was limited, large well-designed studies and further functional investigations are required to confirm our findings.

Polymorphisms of VDR gene and risk of gastric cardiac adenocarcinoma in Chinese population.

Vitamin D receptor (VDR) gene polymorphisms have been reported to increase susceptibility to some malignant tumors, yet the effect on gastric cardiac adenocarcinoma susceptibility remains unknown. Here, we conducted a hospital-based case-control study to examine the correlation of single nucleotide polymorphisms of VDR rs2107301T>C, rs2228570C>T, rs1989969C>T and rs11568820 G>A and gastric cardiac adenocarcinoma susceptibility. A total 330 cases and 608 controls were enrolled in the study. Using ligation detection reaction, we found that the variant alleles of the four polymorphisms were not associated with risk of gastric cardiac adenocarcinoma. Further stratified analyses showed that there was an increased risk associated with VDR rs1989969 polymorphism among patients who were drinking or aged <60. The haplotypes VDR Trs2107301Trs2228570Crs1989969Grs11568820 reduced the susceptibility. This study demonstrated that VDR rs1989969 polymorphism was involved in the carcinogenesis of gastric cardiac adenocarcinoma, especially increased the risk in the younger and alcohol drinking Chinese population.

Tagging polymorphisms of methyl-CpG binding domain 4 and gastric cardiac adenocarcinoma risk in a Chinese population.

Potential effects of genetic factors on carcinogenesis of gastric cardiac adenocarcinoma (GCA) may exist. The present experiment specifically evaluated the genetic influence of single nucleotide in methyl-CpG binding domain 4 (MBD4) on GCA tumorigenesis. A case-control experiment based on hospital recruited 330 GCA patients and 608 non-cancer patients was carried out. We employed ligation detection reaction method to detect the genotypes. The results revealed that MBD4 rs3138373, rs2005618, and rs3138355 mutations had no significant association with the risk of GCA. However, a lower risk of GCA presented in male patients who carried the MBD4 rs3138355 G>A polymorphic loci by the stratified analyses. In general, The MBD4 gene polymorphism could not influence GCA hereditary predisposition. Nevertheless, whether the finding learned from our experiment could apply to other ethnic groups will remain vague until future multicenter studies further test and verify our conclusions.

Interleukin 15 receptor alpha rs2228059 A &gt; C polymorphism decreased risk of gastric cardiac adenocarcinoma in a Chinese population

Gastric cardiac adenocarcinoma (GCA) is one of the common malignant tumors in the world and has a high incidence in China. Both environmental risk factors and genetic factors might play an essential role in the GCA carcinogenesis. We performed a hospital-based case-control study to evaluate the genetic effects of interleukin 15 (IL15) and IL15 receptor alpha (IL15RA) functional single nucleotide polymorphisms (SNPs) on the pathogenesis of GCA. A total of 243 GCA cases and 476 controls were enrolled in this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan(TM) Kit. When the IL15RA rs2228059 AA homozygote genotype was used as the reference group, the CC genotype was correlated with a significantly decreased risk for GCA (CC vs. AA: adjusted OR = 0.61, 95 % CI = 0.37-0.98, p = 0.042). Our results revealed that functional variant IL15RA rs2228059 A > C might attenuate individual's risk of GCA. However, there was no significant association between the other five IL15 SNPs and GCA susceptibility. This present study demonstrated that IL15RA rs2228059 A > C polymorphism might modify GCA susceptibility. The results were based on a limited sample size; future larger studies with more rigorous designs are warranted to validate our findings.

Interleukin 12Brs3212227 T &gt; G polymorphism was associated with an increased risk of gastric cardiac adenocarcinoma in a Chinese population

Gastric cardiac adenocarcinoma (GCA) is one of common malignant tumors in the world. Multiple genes that play critical roles in inflammatory pathways probably are associated with GCA risk. We conducted a hospital-based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): interleukin 9 (IL9) rs31563 C > T, IL9 rs31564 G > T, IL10 rs1800872 T > G, IL12A rs2243115 T > G, IL12B rs3212227 T > G, and IL13 rs1800925 C > T on the development of GCA. Two hundred and forty-three GCA cases and 476 controls were recruited. Their genotypes were determined using a custom-by-design 48-Plex SNPscan kit. IL12B rs3212227 T > G polymorphism was associated with the increased risk of GCA. However, there was no significant association between the other five SNPs and GCA risk. Stratified analyses indicated that the risk of GCA associated with the IL12B rs3212227 T > G polymorphism was evident among female patients and patients who never smoked or consumed alcoholic drinks. These findings indicated that functional polymorphism IL12B rs3212227 T > G might correlate with GCA risk. However, our results were obtained with a limited sample size; the power of our analysis was low. Larger studies are required to confirm the current findings.

The variant interleukin 1f7 rs3811047 G&gt;A was associated with a decreased risk of gastric cardiac adenocarcinoma in a Chinese Han population

To investigate the association between gastric cardiac adenocarcinoma (GCA) and six functional single nucleotide polymorphisms (SNPs) including interleukin 1A (IL1A) rs1800587 C>T, IL1B rs16944 G>A, IL1f7 rs3811047 G>A, IL3 rs40401 C>T, IL3 rs2073506 G>A, and IL7Rα rs6897932 A>G. We performed a hospital-based case-control study to evaluate the genetic effects of these SNPs. A total of 243 GCA cases and 476 controls were enrolled in this study. A custom-by-design 48-Plex SNPscan(TM) kit was used to determine the genotypes. The IL1f7 rs3811047 G>A polymorphism was significantly associated with a decreased risk of GCA either in the single locus analyses or the recessive genetic model. However, there was no significant association between the other five SNPs and GCA risk. These results elucidated that the functional polymorphism, IL1f7 rs3811047 G>A, might contribute to GCA susceptibility. However, the statistical power of our study was limited, large well-designed studies and further functional investigations are needed to confirm our findings.

B-cell Lymphoma 2 rs17757541 C&gt;G Polymorphism was Associated with an Increased Risk of Gastric Cardiac Adenocarcinoma in a Chinese Population

Apoptosis has been considered as a fundamental component in cancer pathogenesis, and related genetic factors might play an important role in gastric cardiac adenocarcinoma (GCA) genesis. We conducted a hospital based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): BCL2 rs17757541 C>G, BCL2 rs12454712 T>C, FAS rs2234767 G>A, FASL/FASLG rs763110 C>T, ERBB2 rs1136201 A>G and VEGFR2/KDR rs11941492 C>T on the development of GCA. A total of 243 GCA cases and 476 controls were recruited for the study and genotypes were determined using a custom-by-design 48-Plex SNPscanTM Kit. The BCL2 rs17757541 C>G polymorphism was associated with increased risk of GCA. However, there was no significant associations with the other five SNPs. Stratified analyses indicated a significantly increased risk of GCA associated with the BCL2 rs17757541 C>G polymorphism among males, older patients and those with a history of smoking or drinking. These findings indicated that the functional polymorphism BCL2 rs17757541 C>G might contribute to GCA susceptibility. However, our results were limited by small sample size. Future larger studies are required to confirm our current findings.

Functional Polymorphisms in FAS/FASL System Contribute to the Risk of Occurrence but not Progression of Gastric Cardiac Adenocarcinoma

Loss of FAS and gain of aberrant FASL expression are common features of malignant transformation. This study was designed to investigate whether the functional polymorphisms of FAS-1377 G/A (rs2234767) and FASL-844 T/C (rs763110) have an effect on the occurrence and progression of gastric cardiac adenocarcinoma (GCA). Associations of the FAS and FASL polymorphisms with GCA were estimated by OR and their 95% confidence intervals using logistic regression. In this study, as compared with the wild type homozygote and heterozygote, either the FAS-1377 AA or FASL-844 CC genotype was associated with increased risk of GCA (OR=1.78; 95% CI, 1.19-2.64 and OR=1.92; 95% CI, 1.46-2.54, respectively). Furthermore, individuals with both the FAS-1377 AA and FASL-844 CC genotypes have a higher risk of GCA (OR=4.09; 95% CI, 2.27-7.37) compared to those with the FAS-1377 GG and FASL-844 TT genotypes. Moreover, the FAS-1377 AA genotype increased the risk of GCA among smokers (OR=1.88; 95% CI, 1.11-3.20) but not among non-smokers, suggesting a potential gene-smoking interaction. This current study suggests that functional polymorphisms in the apoptotic pathway genes FAS and FASL may significantly contribute to the occurrence of GCA.

ERCC1 Gene +262A/C Polymorphism Associated with Risk of Gastric Cardiac Adenocarcinoma in Nonsmokers

Polymorphisms in DNA repair gene may alter an individual's DNA repair capacity and be associated with the risk of various cancers. This study was designed to investigate whether ERCC1 +262A/C and XPF -357A/C polymorphisms affect individual susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). In 389 ESCC patients vs. 778 healthy controls and 262 GCA patients vs. 524 healthy controls in a high incidence region of northern China, ERCC1 +262A/C polymorphism and XPF -357A/C polymorphism were genotyped by the method of polymerase chain reaction ligase detection reaction (PCR-LDR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. Family history of upper gastrointestinal cancers (UGIC) may increase the risk of ESCC and GCA. Allelotype and genotype distributions of ERCC1 +262A/C and XPF -357A/C polymorphisms in ESCC and GCA patients were not significantly different from that in their respective controls (p >0.05). Compared with ERCC1 +262C/C genotype, A/A genotype decreased the risk of GCA in nonsmokers (age, gender and family history of UGIC adjusted odds ratio [OR] = 0.30, 95% confidence interval [CI] = 0.13-0.70). Neither the A/C nor the C/C genotype was associated with the overall risk of ESCC and GCA when compared with the XPF -357A/A genotype. ERCC1 +262A/A genotype may reduce the risk of GCA for nonsmokers. XPF -357A/C polymorphism was not associated with the risk of ESCC and GCA in a population of a high-incidence region in northern China.

Polymorphisms in promoter region of FAS and FASL gene and risk of gastric cardiac adenocarcinoma

AbstractBackground and Aim: The FAS and FASL system play an important role in regulating apoptotic cell death. This study was designed to investigate the correlation of FAS‐1377 G/A, ‐670 A/G and FASL‐844 T/C polymorphisms with susceptibility to gastric cardiac adenocarcinoma in a population of a high‐incidence region of Hebei Province.Methods: FAS‐1377 G/A, ‐670 A/G and FASL‐844 T/C polymorphisms were genotyped by polymerase chain reaction–restriction fragment length polymorphism analysis in 262 gastric cardiac carcinoma (GCA) patients and 524 healthy controls.Results: Family history of upper gastrointestinal cancer (UGIC) might increase the risk of developing GCA (age‐ and sex‐adjusted odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.02–1.86). The overall allelotype and genotype distributions of FAS‐1377 G/A, and FASL‐844 T/C polymorphisms in GCA patients did not significantly differ from that in healthy controls (P &gt; 0.05). Compared with individuals with a FAS‐670 A/A genotype, individuals with an A/G genotype in a smoker group had a lower risk of developing GCA (age, sex, and family history of UGIC adjusted OR = 0.55, 95% CI = 0.34–0.88). When the genotypes of FAS and FASL single nucleotide polymorphisms (SNP) were combined to analyze, no significant correlation was found between these SNP and the risk for GCA development.Conclusion: In the high‐incidence region of Hebei Province, FAS‐1377 G/A and FASL‐844 T/C polymorphisms were not associated with the risk of GCA. However, the FAS‐670 A/G genotype might decrease the risk of GCA for smoker individuals.

Polymorphisms of XRCC1 gene and risk of gastric cardiac adenocarcinoma

X-ray repair cross complementing 1 (XRCC1) protein plays an important role in base excision repair. Single nucleotide polymorphisms (SNPs) in XRCC1 gene may affect DNA repairing ability and genetic susceptibility to cancer. This study was designed to investigate the correlation of XRCC1 Arg194Trp Arg280His and Arg399Gln SNPs with the risk of gastric cardiac adenocarcinoma (GCA). Genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay in 455 patients with GCA and 650 age and sex-matched controls. We did not find any significant difference in allele and genotype distributions of Arg194Trp Arg399Gln between the groups (P > 0.05). However, a significant increase in GCA risk was seen among smokers if they carried at least one XRCC1 280His (Arg280His + His280His) genotype (odds ratio = 1.59, 95%confidence interval = 1.01-2.51) compared with smokers not carrying these genotype. Our results indicated that XRCC1 Arg194Trp and Arg399Gln SNPs might not be associated with the risk of GCA. However, smokers with His allele at codon 280 had a significantly increased risk of GCA.

Etiologic factors of gastric cardiac adenocarcinoma amongmen in Taiwan

To elucidate etiologic associations between Helicobacter pylori (H pylori), lifestyle, environmental factors and gastric cardiac adenocarcinoma (GCA) among men. A hospital-based case-control study was conducted in Taiwan from 2000 to 2009. All cases were newly confirmed as primary GCA. Five controls were selected matching with age, sex, and admission date to each case. Participants were informed of potential risk factors with a structured questionnaire by trained interviewers during hospitalization and provided a blood sample for the determination of H pylori infection. Odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate risk, and a multivariate conditional logistic regression model was performed. All participants recruited for this study were men, consisting of 41 cases and 205 controls. Results of the univariate analysis showed that significant factors associated with the etiology of GCA included H pylori (OR = 2.69, 95% CI = 1.30-5.53), cigarette smoking (OR = 2.28, 95% CI = 1.05-4.96), working or exercising after meals (OR = 3.26, 95% CI = 1.31-8.11), salted food (OR = 2.51, 95%CI = 1.08-6.11), fresh vegetables (OR = 0.28, 95% CI = 0.09-0.80), fruits (OR = 0.19, 95% CI = 0.04-0.89), and rice as principal food (OR = 0.53, 95% CI = 0.30-0.85). Multivariate conditional logistic regression models indicated that a significantly elevated risk of contracting GCA was associated with working or exercising after meals (OR = 3.18, 95% CI = 1.23-9.36) and H pylori infection (OR = 2.93, 95% CI = 1.42-6.01). In contrast, the consumption of fresh vegetables (OR = 0.22, 95% CI = 0.06-0.83), fruits (OR = 0.28, 95% CI = 0.09-0.79) and rice as principal food (OR = 0.48, 95% CI = 0.24-0.93) remained as significant beneficial factor associated with GCA. Working or exercising after meals and H pylori infection increase the risk of GCA, but higher intakes of rice, fresh vegetables and fruits reduce the risk.

Polymorphisms of the DNA Repair Gene XPA and XPC and its Correlation With Gastric Cardiac Adenocarcinoma in a High Incidence Population in North China

Investigated the association of DNA repair gene xeroderma pigmentosum group A(XPA) and C(XPC) polymorphisms with the risk of gastric cardiac adenocarcinoma (GCA) in a high incidence region in north China. Polymorphisms of a number of DNA repair genes may contribute to variations in DNA repair capacity and genetic susceptibility to different cancers. Two single nucleotide polymorphisms of XPA and 3 single nucleotide polymorphisms of XPC were genotyped in 253 GCA patients and 612 healthy controls. Family history of upper gastrointestinal cancer may increase the risk of developing GCA. Compared with A/A genotype, A/G+G/G genotype of XPA A23G significantly decreased the risk of developing GCA especially in nonsmoker group. The genotype and allelotype distributions of XPC intron 9 PAT+/- and exon 15 Lys939Gln in GCA patients were not significantly different from that in healthy controls (P>0.05). T allelotype frequencies of XPC exon 8 Val499Ala in GCA patients was significantly lower than that in healthy controls (P<0.05). The C/T genotype frequency of XPC exon 8 in GCA patients (35.6%) was significantly different from that in healthy controls (46.1%) (P=0.01). Compared with individuals with C/C genotype, individuals with T allele (C/T or T/T genotype) had significantly lower risk in developing GCA. We also found that polymorphisms of this 3 XPC locus were in linkage disequilibrium. XPA A23G and XPC exon 8 Val499Ala polymorphisms may be useful markers for identifying individuals at risk of developing GCA in the high incidence region of north China.

Personal history and family history as a predictor of gastric cardiac adenocarcinoma risk: a case-control study in Taiwan.

To clarify the risk of gastric cardiac adenocarcinoma for patients with a personal and/or family history of gastrointestinal diseases. The present study was a hospital-based case-control study conducted from 1992 to 1997 in Kaohsiung, Taiwan, consisting of 176 cases and 579 controls matched by age, sex, and time of hospitalization. With informed oral consent, each subject completed a structured questionnaire during hospitalization regarding sociodemographic status, lifestyle, and health history. The response rate was 98%. Adjusting for age, sex, years of schooling, socioeconomic status, body mass index (BMI), and smoking. Multivariate logistic regression models indicated a reduced effect for patients with a personal history of duodenal ulcer (DU) (odds ratio (OR) = 0.8, 95% confidence interval (CI) 0.5-0.9). No association was observed between the risk of gastric cardiac cancer and other forms of gastric disease. Furthermore, we also demonstrated that individuals with a family history of gastric cancer had a higher risk than those who lacked a family history (OR = 2.5, 95% CI 1.3-4.8). Our findings provide further evidence that individuals with DU history are less likely to have gastric cardiac cancer, and we infer that Helicobacter pylori (H. pylori) infection (85-95% DU patients infected with H. pylori) alone may not be sufficient to cause gastric cardiac adenocarcinoma. In addition, this study also suggests that a positive family history of gastric cancer may predict an increased risk for the disease.