Gastric Cancer In Chinese Population Research Articles

Association between the polymorphisms in XPG gene and gastric cancer susceptibility in Chinese populations: A PRISMA-compliant meta-analysis.

Background:Several previous studies were carried out on the association between xeroderma pigmentosum group G (XPG) gene polymorphisms (including rs873601 G>A, rs2094258 C>T, rs2296147 T>C, and rs751402 C>T) and the risk of gastric cancer in Chinese populations. However, their conclusions were not consistent. Therefore, this meta-analysis was performed by us to investigate the association between the 4 potentially functional single nucleotide polymorphisms (SNPs) of XPG gene and gastric cancer risk.Methods:The eligible literatures were identified through PubMed, Embase, Ovid MEDLINE, Web of Science, CNKI, and Wan fang databases up to July 2017. Finally, 5 studies for rs873601, 7 studies for rs2094258, 4 studies for rs2296147, and 8 studies for rs751402 were used for the current meta-analysis.Results:Of the 4 included SNPs, only rs751402 was showed to be associated with the risk of gastric cancer [C vs T, odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.04–1.29; CC + CT vs TT, OR = 1.23, 95% CI = 1.00–1.52; CC vs CT + TT, OR = 1.15, 95% CI = 1.05–1.27; CC vs TT, OR = 1.35, 95% CI = 1.06–1.72; CC vs CT, OR = 1.13, 95% CI = 1.02–1.25].Conclusion:The current meta-analysis demonstrated that the XPG gene polymorphism rs751402 was associated with increased susceptibility to gastric cancer in Chinese populations. However, studies with a larger number of subjects among different ethnic groups are needed to further validate the results.

Association of 758 G/A polymorphism of 3'untranslated region of prohibitin with risk of gastric cancer.

A polymorphic variant allele (T-allele) in the 3'-UTR of prohibitin (C-to-T at nucleotide 729) was reported to be associated with an increased risk of breast cancer. However, the association between the 3'-UTR polymorphism of prohibitin and the susceptibility to gastric cancer remains unknown. Thus, we investigated the distribution of prohibitin genotypes in Chinese patients with gastric cancer and subsequently analyzed the association between the 3'-UTR polymorphism of prohibitin and the risk of gastric cancer in that population. The distribution of 3'-UTR polymorphism of prohibitin in 82 gastric cancer patients was determined by sequencing and compared with that of 171 healthy controls. Luciferase reporter assay was used to investigate the effect of 3'-UTRs variant on PHB expression. Our study discovered two major polymorphic sites in the 3'-UTR of prohibitin (C-to-T at nucleotide 729 and G to A at nucleotide 758). The C/T polymorphism at 729 site was not associated with the increased risk of gastric cancer (P=.961, OR=1.044, 95%CI: 0.187-5.818); however, G/A polymorphism at nucleotide 758 increased the risk of gastric cancer (P=.017, OR=1.923, 95%CI: 1.119-3.305). Luciferase reporter constructs containing the 758A allele showed higher luciferase activity compared with the wild-type allele, which indicated that 758 G>A in 3'-UTR increased PHB expression. The G to A transition but not the C-to-T transition in the 3'-UTR of prohibitin was associated with an increased risk of gastric cancer in Chinese population.

A functional SNP rs1892901 in FOSL1 is associated with gastric cancer in Chinese population

FOSL1 (FOS like antigen 1) is one kind of proto-oncogene, and may play a vital role in carcinogenesis of multiple cancers. However, studies about the relationship between SNPs in FOSL1 and gastric cancer are still lacking. Thus, we investigated the association of seven SNPs in FOSL1 with gastric cancer using case-control design in a two-stage strategy (Screening stage: 1,140 gastric cancer cases and 1,547 controls; Replication stage: 1,006 cases and 2,273 controls). We found that rs1892901 was significantly associated with increased risk of gastric cancer in additive model (adjusted OR = 1.25, 95%CI: 1.06–1.47, P = 0.008) in first stage. Following replication results revealed that the relationship between rs1892901 and gastric cancer risk was consistent with our primary results. In silico analysis showed that rs1892901 might alter multiple regulatory motifs, disturb protein binding, and affect the expression of FOSL1 and other important gastric cancer-related genes such as EGR1, CHD, EP300, FOS, JUN and FOSL2. Our findings indicated that functional SNP rs1892901 in FOSL1 might affect the expression of FOSL1, and ultimately increase the risk of gastric cancer. Further functional studies and large-scale population studies are warranted to confirm our findings.

Functional Genetic Variants in SPHK1 Affect Susceptibility to Gastric Cancer in a Chinese Population.

An escalating number of studies have provided identified evidence that sphingosine kinase 1 (SPHK1) plays an essential role in carcinogenesis. This present study was devised to seek the possible correlation of two tag single-nucleotide polymorphisms (SNPs) in SPHK1 (rs3744037 T>C, rs346801 C>T) with the susceptibility to gastric cancer (GC). This present case-control study was comprised of 710 patients with GC and 710 gender- and age-matched cancer-free individuals. The genotypes of the individuals were acquired by the TaqMan-MGB method. SPHK1 mRNA level was examined in 60 paired cancerous and noncancerous tissues using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Our results suggested that the variant genotype T allele of SPHK1 rs346801 increased the GC risk in the study population [CT vs. CC, odds ratio (OR) = 1.385, 95% confidence interval (CI) = 1.096 - 1.751; TT vs. CC, OR = 2.502, 95% CI = 1.078 - 5.806; CT+TT vs. CC, OR = 1.434, 95% CI = 1.140 - 1.804]. Furthermore, in stratified analyses, rs346801 variant genotypes were associated with a conspicuous risk of GC in younger individuals (< 62 years), females, non-smokers, and individuals from rural areas. In addition, the carriers with variant genotype CT, TT, and CT+TT were observed to possess the higher SPHK1 messenger RNA levels than those with CC genotype in GC specimens. These results strongly demonstrated that the SPHK1 rs346801 C>T polymorphism may contribute to the susceptibility to gastric cancer in Chinese population and affect the expression of SPHK1 and, therefore, may act as a novel biomarker for predicting gastric cancer.

Profiling chemotherapy-associated myelotoxicity among Chinese gastric cancer population receiving cytotoxic conventional regimens: epidemiological features, timing, predictors and clinical impacts.

Objectives: We aim to evaluate the epidemiological features, timing, predictors and clinical impacts of chemotherapy-associated myelotoxicity in Chinese gastric cancer population receiving six established cytotoxic conventional regimens (CF/XP, EC(O)F/EC(O)X, DC(O)F/DC(O)X, PC(O)F/PC(O)X, FOLFOX4, or mFOLFOX7/XELOX).Patients and methods: A 4-year multicenter, prospective, observational study was conducted in multiple hospitals/institutes spanning three major regions in China. A total of 1,285 patients with gastric cancer, treated with six selected regimens between 2010 and 2014 were included. Kaplan-meier analysis was applied to estimate the time to develop myelotoxicity events for each regimen. Multivariable logistic regression model was built to identify predictors associated with chemotherapy-induced myelotoxicity, evaluating detailed specific factors of patients, disease and treatment patterns.Results: Triplet regimens were associated with more moderate-to-severe myelotoxicity events than doublet regimens. DC(O)F/DC(O)X group presented with moderate-to-severe anaemia, thrombocytopenia, and leukopenia earlier than other regimen groups, with median time of 3.5, 4.8 and 3.3 cycles, respectively. PC(O)F/PC(O)X group had a shortest time to develop Moderate-to-Severe neutropenia (median time, 3.3 cycles). Multivariate analysis identified several independent predictors for moderate-to-severe myelotoxicity, including: baseline Hb<12.0 g/dL, male gender, KPS<80, previously treated with surgery, tumor located at gastroesophageal junction(GEJ), DC(O)F/DC(O)X regimen, palliative intent, triplet combination therapy and No. of cycles received≥4. Dose reductions≥20% occurred in 16.7% of patients and treatment delays≥7 days presented in 21.1% of patients, resulting in patients receiving an actual average Relative Dose Intensity (RDI) of 0.733.Conclusions: Myelotoxicity events were frequently observed within the gastric cancer population undertaking multicycle polychemotherapy. Predictive models based on risk factors identified for moderate-to-severe myelotoxicity should enable the targeted use of appropriate supportive care in an effort to facilitate the delivery of full chemotherapy doses on schedule.

NDRG4 hypermethylation is a potential biomarker for diagnosis and prognosis of gastric cancer in Chinese population.

In order to assess whether N-Myc downstream regulated gene 4 (NDRG4) methylation was associated with the diagnosis and prognosis of gastric cancer, we measured the methylation of NDRG4 promoter and gene body regions among 110 gastric cancer patients using quantitative methods (MethyLight and pyrosequencing). Both NDRG4 promoter and gene body methylation levels were increased in tumor tissues than paired adjacent normal tissues (P < 0.001). NDRG4 gene body methylation was found to be significantly associated with age and tumor differentiation. NDRG4 promoter hypermethylation was proved to be a predictor of poor overall survival. However, opposite result was observed among The Cancer Genome Atlas (TCGA) cohort. The findings from gastric cell lines and public databases have suggested that NDRG4 methylation level was inversely associated with NDRG4 transcription level. Subsequent luciferase reporter gene assay showed that promoter CpG island but not gene body CpG island was able to upregulate gene expression. Collectively, NDRG4 promoter hypermethylation contributed to the risk of gastric cancer and predicted a poor prognosis in Chinese gastric cancer patients. Moreover, the combined methylation levels of NDRG4 promoter and gene body served as diagnostic biomarkers in gastric cancer.

Validation of the Memorial Sloan Kettering Cancer Center nomogram to predict disease-specific survival in a Chinese gastric cancer population receiving postoperative chemoradiotherapy after an R0 resection.

The widely validated Memorial Sloan Kettering Cancer Center (MSKCC) nomogram for gastric carcinoma (GC) was developed based on patients who received R0 resection only. The purpose of the current study was to assess the performance of this nomogram in Chinese patients who received postoperative chemoradiotherapy (CRT) after an R0 resection for GC. From 2006 to 2015, the clinical data of 150 eligible patients were retrospectively collected from the Fudan University Shanghai Cancer Center (FUSCC) and used for external validation. The nomogram was validated by means of the concordance index (CI) and a calibration plot. The CI for the nomogram was 0.657, which was lower than the CI of the nomogram for patients who received surgery alone (0.80). In the calibration plot, the gap between the observed and the predicted survival gradually increased as the predicted 5-year disease-specific survival (DSS) decreased. Thus the MSKCC nomogram for GC significantly underestimated the survival of patients in the FUSCC cohort, especially the survival of patients whose predicted 5-year DSS was less than 50%. The current study indicates the potential for the nomogram to be developed as an ideal tool to identify target patients for postoperative CRT.

TNF-α-308/-238 polymorphisms are associated with gastric cancer: A case-control family study in China

Associations of TNF-α-308 (rs1800629) and -238 (rs361525) with gastric cancer had the inconsistent indication among different populations. In this case-control family study, 47families were determined with the probands diagnosed with gastric cancer (case family, n=296), accordingly 47families without gastric cancer were matched with the case families by multivariate distribution of age, sex, social class, and pedigree size (control family, n=319). Polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) was used to identify the TNF genotype. Chi-square test was used to compare the groups regarding genotype and the allele frequencies, HWE test for Hardy-Weinberg equilibrium. The frequencies of TNF-α-308 GA and AA genotypes were significantly higher in case family than that in control family. The risk of gastric cancer was increased in GA and AA carriers in the first degree (OR=2.06, 95% CI=1.20-3.51 and OR=4.89, 95% CI=2.74-8.74), however the similar result was not found in the second degree. Helicobacter pylori infection status were significantly associated with risk of gastric cancer in first-degree relatives (OR=1.96, 95% CI=1.26-3.05) while no statistical significance was noted in the second-degree relatives. Haplotypes of TNF-α-308/-238 alleles, GA/GG, AA/GG and AA/GA indicated the susceptibilities to gastric cancer with OR and 95% confident intervals resulting 2.07 (1.34-3.21), 4.49 (2.74-7.33) and 4.98 (1.76-14.01) respectively. TNF-α-G308A (rs1800629) polymorphisms are associated with gastric cancer in Chinese population. Haplotypes of TNF-α-308/-238 GA/GG, AA/GG and AA/GA increase the susceptibilities to gastric cancer. The first-degree relatives are more likely to develop into gastric cancer with TNF-α-G308 polymorphisms and H.pylori positive than the second-degree are.

Correlation Between Interleukin-1β-511 C/T Polymorphism and Gastric Cancer in Chinese Populations: A Meta-Analysis.

BackgroundSeveral studies have indicated that interleukin (IL)-1β-511 C/T polymorphism may contribute to individual susceptibility to gastric cancer, but the results vary among regions and races. No relevant meta-analysis has been conducted in a Chinese population. Therefore, we performed the current meta-analysis to investigate the possible correlation between IL-1β-511 C/T polymorphism and gastric cancer susceptibility in Chinese subjects.Material/MethodsPubMed, EmBase, Cochrane Library, Chinese Biology Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for case-control studies published before 21 January 2015 and investigating a correlation between IL-1β-511 C/T polymorphism and gastric cancer susceptibility. Two investigators independently screened the studies, extracted data, and evaluated the quality of included studies with the Newcastle-Ottawa scale. Meta-analysis was conducted with STATA 12.0.ResultsA total of 27 articles from 28 case-control studies were collected. Meta-analysis showed that IL-1β-511C/T polymorphism was related to increased susceptibility to gastric cancer in Chinese subjects [T vs. C: OR=1.21, 95%CI (1.07–1.37), P<0.01; TT vs. CC: OR=1.41, 95%CI (1.11–1.80), P<0.01; CT vs. CC: OR=1.26, 95% CI (1.05–1.50), P<0.01; TT+CT vs. CC: OR=1.31, 95%CI (1.08–1.58), P<0.01; and TT vs. CT+CC: OR=1.24, 95%CI (1.05–1.47), P<0.01]. Subgroup analysis showed a significant correlation between IL-1β-511C/T polymorphism and susceptibility to gastric cancer in residents of southern China and in patients with intestinal-type gastric cancer, but not in residents of northern China or in patients with diffuse gastric cancer. Moreover, H. pylori-infected subjects carrying T (CT+TT) exhibited a relatively higher risk of GC [OR=2.4, 95% CI (1.2–5.1), P=0.02].ConclusionsIL-1β-511C/T polymorphism is significantly associated with increased susceptibility to gastric cancer in residents of southern China and in intestinal-type gastric cancer. We also found a synergistic interaction between IL-1β-511C/T polymorphism and H. pylori infection in the development of GC.

Association between microRNA-499 polymorphism and gastric cancer risk in Chinese population

Single-nucleotide polymorphisms in microRNAs are related to the occurrence, development and prognosis of cancer. The aim of the present study is to investigate the possible influence of the miR-499(rs3746444) polymorphism on the risk of gastric cancer in Chinese population. A total of 363 GC patients and 969 cancer-free controls were enrolled in this study. The genotypes were obtained using MassARRAY method. The results showed that, compared with T allele, C allele was associated with a significantly increased risk of GC (OR=1.491, 95% CI=1.155-1.923, P=0.002). Moreover, a significantly increased risk of GC in subjects with the TC genotype was observed (adjusted OR of 1.559, 95% CI=1.148-2.117, P=0.004), compared with the wide type TT. We also found that basically dominant model (TT vs. TC+CC) was suitable for the association between rs6513497 and the risk of GC (OR=1.568, 95% CI=1.173-2.097, P=0.002). However, the same association was also shown in males and females. Meanwhile, rs3746444 was associated with the tumor size of GC patients. The present study indicated that miR-499 rs3746444 might contribute to GC risk and this SNP could be developed as a biomarker for GC prediction.

Complement receptor 1 genetic variants contribute to the susceptibility to gastric cancer in chinese population.

As the receptor for C3b/C4b, type 1 complement receptor (CR1/CD35) plays an important role in the regulation of complement activity and is further involved in carcinogenesis. This study aimed to elucidate the association of CR1 genetic variants with the susceptibility to gastric cancer in Chinese population. Based on the NCBI database, totally 13 tag single nucleotide polymorphisms (SNPs) were selected by Haploview program and genotyped using iPlex Gold Genotyping Assay and Sequenom MassArray among 500 gastric cancer cases and 500 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression to evaluate the association of each SNP with gastric cancer. Of all selected Tag SNPs , CR1 rs9429942 T > C was found to confer to the risk of developing gastric cancer. Compared with the carriers with rs9429942 TT genotype, those with CT genotype had 88% decreased risk of developing gastric cancer with OR (95%CI) of 0.12 (0.03-0.50). Generalized multifactor dimensionality reduction (GMDR) analysis revealed a significant three-way interaction among rs75422544 C > A, rs10494885 C > T and rs7525160 G > C in the development of gastric cancer with a maximum testing balance accuracy of 56.07% and a cross-validation consistency of 7/10 (P = 0.011). In conclusion, our findings demonstrated the genetic role of CR1 gene in the development of gastric cancer in Chinese population.

CD226 rs727088A>G polymorphism increases the susceptibility to gastric cancer in Chinese populations

Gastric cancer (GC) is one of the most common cancers worldwide, especially in Asia. The development of GC is a multifactorial process and numerous studies have linked genetic variation to GC risk. In this study, we evaluated the effects of single nucleotide polymorphisms (SNPs) of CD226 on GC susceptibility in Chinese populations including 687 cancer patients and 936 control subjects. We found that the G allele of the rs727088A>G polymorphism in the 3′-untranslated region of CD226 was significantly associated with risk of GC using logistic regression (P<10−3). GC patients who harbored the rs727088G allele had significantly increased cancer risk (odds ratio=1.43, 95% confidence interval=1.23–1.67) compared with those patients harboring the rs727088A allele. Moreover, functional relevance was further performed that individuals carrying the rs727088G allele were correlated with lower expression level of CD226 than individuals carrying the rs727088AA homozygous genotype. These findings indicated that functional polymorphism rs727088A>G in CD226 might modify the susceptibility for the development of GC.

The tag SNP rs10746463 in decay-accelerating factor is associated with the susceptibility to gastric cancer

BackgroundComplement activation involved in the innate immunity and adaptive immunity and further contributed to the development of tumor growth. This study aimed to investigate the association of genetic variants in complement 3 (C3) and decay-accelerating factor (DAF) genes with the risk of gastric cancer. MethodsThis case-control study included 500 gastric cancer patients and 500 cancer-free controls. Based on the Chinese population data from HapMap database, we used Haploview 4.2 program to select candidate tag SNPs. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression to evaluate the association of each genetic variant with the risk of gastric cancer. ResultsAmong 12 tag SNPs of C3, no correlation was observed between C3 genetic variants and risk of gastric cancer. For tag SNPS of DAF, logistic regression analysis revealed that the carriers with DAF rs10746463 AA genotype had a significantly increased risk for developing gastric cancer (OR=1.46, 95% CI=1.01–2.10) when compared with GG genotype, but those carrying with rs10746463 AG genotype didn’t (OR=1.31, 95% CI=0.98–1.75). When stratified by smoking status, we found that the risk of gastric cancer was associated with rs10746463 GA or AA genotype carriers among smoker with OR (95% CI) of 1.64 (1.06–2.54), but not among non-smoker (OR=1.37, 95% CI=0.97–1.94). ConclusionDAF rs10746463 polymorphism effects on the risk of developing gastric cancer in Chinese population.

Correlation between SNPs in CDH1 and gastric cancer in Chinese population

BackgroundMany recent studies revealed that the single nucleotide polymorphisms have considerable effects on the susceptibility of cancer, such as prostate cancer, lung cancer and gastric cancer. The E-cadherin, a calcium-dependent transmembrane glycoprotein encoded by CDH1 gene, is critical for epithelial construction, intercellular adhesion and cell migration. Some associations have been reported between single nucleotide polymorphisms and gastric cancer in the Chinese population.ObjectiveTo investigate whether the single nucleotide polymorphism in CDH1 gene is associated with the susceptibility of gastric cancer in the Chinese population.Material and methodsThe genotypes of 5 known single nucleotide polymorphisms (rs33935154, rs121964871, rs121964874, rs121964875, rs121964876) were determined in 359 gastric cancer patients and 368 healthy controls. High resolution melting curve detection and sequencing analysis were used in the present study.ResultsThere is a statistical significance in the rs121964871 C>G polymorphism between gastric cancer patients and healthy controls (OR=1.769, 95%CI: 1.051–2.976). Elderly male individuals (>50 years of age) carrying this risk factor may be more susceptible to gastric cancer.ConclusionsThe results indicated that the rs121964871 C>G polymorphism is associated with the susceptibility of gastric cancer in the Chinese population, with some age and sex-dependent tendencies observed.

Methylation status of blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population.

To evaluate the relationship between methylation status of blood leukocyte DNA and risk of gastric cancer, a population-based study was conducted in Linqu County. Methylation levels of IGFII and N33 were determined by quantitative methylation-specific PCR. The temporal trend of methylation levels during gastric cancer development was investigated in 133 gastric cancer cases from two cohorts with pre- and/or post-gastric cancer samples. As the references of pre-GCs, 204 intestinal metaplasia (IM) or dysplasia (DYS) subjects who did not progress to gastric cancer during the follow-up period were selected. Meanwhile, 285 subjects with superficial gastritis/chronic atrophic gastritis (SG/CAG) were also selected as controls. IGFII median methylation level was significantly higher in gastric cancer cases than those with SG/CAG (61.47% vs. 49.73%; P < 0.001). IGFII and N33 methylation levels were elevated at least 5 years ahead of clinical gastric cancer diagnosis comparing with SG/CAG (63.38% vs. 49.73% for IGFII, 9.12% vs. 5.70% for N33; all P < 0.001). Furthermore, the frequency of hypermethylated IGFII was markedly increased in IM or DYS subjects who progressed to gastric cancer in contrast to those who remained with IM and DYS, and adjusted ORs were 12.52 [95% confidence interval (CI), 3.81-41.15] for IM and 10.12 (95% CI, 2.68-38.22) for DYS. Similar results were also found for N33 in subjects with IM (OR, 3.77; 95% CI, 1.20-11.86). Our findings suggested that hypermethylated IGFII and N33 in blood leukocyte DNA were associated with risk of gastric cancer in a Chinese population. IGFII and N33 methylation status may be related to gastric carcinogenesis.

IFRD1 polymorphisms and gastric cancer risk in a Chinese population.

The association between gene polymorphisms of IFRD1 and gastric cancer is not clear. The aim of this study was to investigate the association between IFRD1 polymorphisms and gastric cancer in Chinese population. Fifty-three consecutive patients with the diagnosis of gastric cancer were defined as the case group, and another 50 healthy donors were denoted as the control group. About 4 ml of peripheral blood was collected from each donor for extracting DNA. Finally, IFRD1 rs7818, rs3807213, and rs6968084 SNPs were detected with polymerase chain reaction. C/C genotype distribution frequencies of rs6968084 and rs7817 in gastric cancer patients were similar with the controls (OR 0.192, 95 % CI 0.513-2.769, P = 0.683 and OR 2.075, 95 % CI 0.744-5.792, P = 0.16, respectively). Patients with gastric cancer had a significantly higher frequency of rs3807213 C allele and rs3807213 C/C genotype than controls. (OR 4.028, 95 % CI 1.513-10.72, P = 0.004) (OR 3.759, 95 % CI 1.521-9.294, P = 0.003). This study suggests that the SNPs of IFRD1 rs7818 and rs6968084 have nothing to do with the gastric cancer susceptibility. The allele gene C and genotype C/C of rs3807213 SNP are involved in susceptibility to gastric cancer, but there were no relations when subgroup stratified all the three SNPs according to pathological stages.

The effect of MUC1 rs4072037 functional polymorphism on cancer susceptibility: evidence from published studies.

Genome-wide association studies have identified a susceptibility variation MUC1 rs4072037 for gastric cancer in Chinese population. Subsequent case-control studies have reported this association in other populations. However, the results remain controversial and ambiguous. The aim of this study is to provide a precise quantification for the association between MUC1 rs4072037 variation and the risk of cancer. We performed pooled analysis of 10 case-control designed studies including 4,220 cases and 6,384 controls. Odds ratios (OR) and 95% confidence interval (95%CI) were calculated to assess strength of association in overall studies and in subgroup analysis stratified by ethnicity and cancer types. All statistical analyses were performed by Manager 5.0 and Stata 12.0 software. Overall, the MUC1 rs4072037 polymorphism was associated with risk of cancer in all genetic models (G vs A: OR = 0.71, 95%CI: 0.63–0.80, p<0.01; GA vs AA: OR = 0.61, 95%CI:0.55–0.67, p<0.01; GG vs AA: OR = 0.58, 95%CI: 0.47–0.71, p<0.01; AG+AA vs GG: OR = 0.60, 95%CI: 0.55–0.60, p<0.01; GG vs AG+AA: OR = 0.70, 95%CI: 0.58–0.85, p<0.01). Further, subgroup analysis based on ethnicity suggested MUC1 rs4072037 polymorphism had a subtly reduced cancer risk among Asian population, and stratified analysis by cancer types showed significantly decreased risk of gastric cancer in all genetic models. In conclusion, MUC1 rs4072037 polymorphism may be used as potential biomarker for cancer susceptibility particularly for gastric cancer and for Asian population.

No association between single nucleotide polymorphisms in pre-mirnas and the risk of gastric cancer in Chinese population.

Accumulating evidence has demonstrated that miRNAs contribute to various genetic and epigenetic modifications in the pathogenesis of gastric cancer (GC). Recent studies focused on the four single nucleotide polymorphisms (SNPs) of pre-miRNAs including rs11614913, rs3746444, rs2910164, and rs2292832. It was suggested that these four SNPs were significantly associated with the risk of GC and were described as candidate susceptibility factors. However, the previous results show conflicting findings. The aim of this study was to investigate whether these four SNPs are associated with GC in Chinese Han population. Genotype frequencies of these four SNPs of pre-miRNAs in 220 GC patients and 530 control subjects were performed using a PCR-RFLP assay. No significant differences in genotype and allelic distribution were found in these four SNPs between GC and control subjects in the Chinese Han population. However, we found that the allelic frequency distributions of control subjects in these four SNPs were significantly different from those of the Japanese and the Koreans (All the P<0.05). The four SNPs did not show any significant correlation with the development of GC in the Chinese Han population, based on the current study.

Polymorphisms of the TLR4 gene and risk of gastric cancer

ObjectiveToll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene–environmental interactions on the risk of GC in Northeastern China. MethodsWe genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models. ResultsIndividuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR=0.33, 95% CI 0.18–0.60, P<0.001 and adjusted OR=0.37, 95% CI 0.21–0.67, P=0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC. ConclusionOur data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC.

Genetic variation rs10484761 on 6p21.1 derived from a genome-wide association study is associated with gastric cancer survival in a Chinese population

A recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan–Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate the association between the SNP rs10484761 and gastric cancer survival. In the dominant model, those who carry TC/CC genotypes had a significant shorter survival time (log-rank P=0.005), especially in the subgroups of aged male patients, cardia intestinal tumor (HR=1.41, 95% CI=1.08–1.84 for cardia cancer and HR=1.64, 95% CI=1.14–2.37 for intestinal-type), tumor size≤5cm (HR=1.41, 95% CI=0.56–0.99), T1 depth invasion (HR=2.34, 95% CI=1.20–4.56), lymph node metastasis (HR=1.51, 95% CI=1.19–1.96), no distant metastasis (HR=1.33, 95% CI=1.05–1.68), TNM stage III+IV (HR=1.50, 95% CI=1.13–1.98), and with chemotherapy (HR=1.53, 95% CI=1.17–1.99). The results indicated that SNP rs10484761 was associated with prognosis of gastric cancer, suggesting that this genetic variant may serve as a potential marker to predict the survival of gastric cancer in Chinese population.