Variant TP53BP1 rs560191 G>C is associated with risk of gastric cardia adenocarcinoma in a Chinese Han population

Objective:To investigate the association between gastric cardia adenocarcinoma（GCA） and ten functional single nucleotide polymorphisms（SNPs）,including TP53BP1 rs560191 G>C,CASP8 rsl035142 G>T,CASP7 rs3127075 G>C,CASP7 rs7907S19 C>A,and six C1orf10/CRNN variants.We performed a hospitalbased case-control study to evaluate the genetic effects of these SNPs.Methods:Two hundred and forty-three GCA cases and 476 controls were enrolled in this study.A customby-design 48-Plex SNPscan^TM Kit was used to determine their genotypes.Results:When the TP53BP1 rs560191 GG homozygote genotype was used as the reference group,the GC genotype was associated with a significantly increased risk of GCA.The CC genotype was not associated with the risk of GCA compared with the GG genotype.None of the CASP8 rs1035142 G>T,CASP7rs3127075 G>C,CASP7 rs7907519 C>A or the six C1orf10/CRNN polymorphisms showed a significant difference in genotype distributions between the cases and the controls.Conclusions:The results demonstrated that the functional polymorphism TP53BP1 rs560191 G>C might contribute to GCA susceptibility.However,the statistical power of our study was limited.Large,welldesigned stuthes and further functional investigations are needed to confirm our findings.     

Interleukin 15 receptor alpha rs2228059 A > 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.     

E-selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population

Host immune responses are critical steps for carcinogenesis. Single nucleotide polymorphisms (SNPs) in immunoregulatory genes may influence gastric cancer risk. We performed a genotyping analysis for immunoregulatory genes in 311 gastric cancer cases and 425 controls from a Chinese population. We found that there were significant differences of E‐selectin variant rs5361 (A>C) and FCGR2A variant rs1801274 (T>C) between cases and controls (P = 0.022 and P = 0.0001, respectively). Logistic regression analysis indicated that genotype of E‐selectin rs5361AC increased the risk of gastric cancer significantly (P = 0.026, adjusted Odds ratio (OR) = 2.84, 95% confidence interval (CI) = 1.13–7.12). C allele of E‐selectin rs5361 showed a significant increased frequency in cases (P = 0.023). However, the E‐selectin variant did not affect the protein expression. E‐selectin protein was observed not only in tumor interstitial vascular endothelial cells, but also in gastric cancer cells at primary and metastatic sites. The protein was associated with clinicopathological characteristics of gastric cancer, such as age (P = 0.008), tumor size (P = 0.027), differentiation (P = 0.000), and tumor‐node‐metastasis (TNM) stage (P = 0.006). CT and CC + CT genotypes of FCGR2A variant rs1801274 increased gastric cancer risk (P = 0.000, adjusted OR = 1.92, 95%CI = 1.36–2.72; P = 0.003, adjusted OR = 1.68, 95%CI = 1.20–2.35, respectively). Interleukin‐4 receptor (IL‐4R) variant rs2107356 presented negative correlations to E‐selectin variant rs5361 and FCGR2A variant rs1801274 (P = 0.035 and P = 0.023) in conferring susceptibility to gastric cancer. We concluded E‐selectin variant rs5361 and FCGR2A variant rs1801274 were significantly associated with gastric cancer risk. Expression of E‐selectin protein would promote progression of gastric cancer. © 2011 Wiley Periodicals, Inc.     

Variant alleles of TGFB1 and TGFBR2 are associated with a decreased risk of gastric cancer in a Chinese population

Growing evidence suggests that the transforming growth factor beta (TGF-beta) signaling pathway occupies a central position in the signaling networks that control cell growth and differentiation. TGF-beta1 and its receptor TGF-betaRII have been correlated with the development of certain forms of cancer, including gastric cancer. We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we genotyped C-509T and Leu10Pro polymorphisms in TGFB1 and G-875A variant in TGFBR2, using the primer-introduced restriction analysis (PIRA)-PCR assay, in a case-control study of 675 gastric cancer cases and 704 healthy controls in a Chinese population. We found that the variant alleles of the promoter polymorphisms, TGFB1 C-509T and TGFBR2 G-875A, were associated with a significantly decreased risk of gastriccancer [adjusted odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52-0.82 for -509CT/TT and adjusted OR = 0.67, 95% CI = 0.53-0.85 for -875GA/AA]. Furthermore, subjects with both variant genotypes of the TGFB1 C-509T and TGFBR2 G-875A were associated with a significantly (56%) decreased risk of gastric cancer (adjusted OR = 0.44, 95% CI = 0.32-0.62). These findings indicate, for the first-time, that the functional variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer susceptibility.     

Uracil-DNA glycosylase (UNG) rs246079 G/A polymorphism is associated with decreased risk of esophageal cancer in a Chinese population

The prognosis of relapsed or refractory aggressive non-Hodgkin’s lymphoma (NHL) after front-line therapy remains poor. The development of more effective and less toxic salvage regimens remains a major challenge. Survivin is a member of the family of inhibitors of apoptosis, and survivin was associated with short survival and bad prognosis. This study was to evaluate the efficacy of GDP regimen (gemcitabine, dexamethasone and cisplatin) on relapsed or refractory aggressive NHL and various prognostic factors with special emphasis on survivin and observe the . Forty-six patients with relapsed and refractory NHL, intermediate or high-grade NHL (Revised European American Lymphoma Classification), who at least one regimen were enrolled into this study, which was carried out at Department, , Tanta University from July 2012 to July 2014. The patients were treated with GDP regimen (gemcitabine 1,000 mg/m² on days one and eight, dexamethasone 40 mg on days 1–3, and cisplatin 25 mg/m² on days 1–3) every 3 weeks. The efficacy and adverse events were evaluated according to the WHO criteria. All patients were assessed for efficacy and toxicity. The overall response rate was 58.7 %. Fourteen patients showed a complete response, thirteen partial responses, twelve stable diseases, and seven progressive disease. The 24-month overall survival was 50.8 %. Survivin is associated with low overall response and shorter overall survival. Grade 3 anemia was observed in four patients, grade 3 leucopenia in six patients, grade 3 neutropenia in six patients, and grade 3 thrombocytopenia in four patients. Non-hematologic toxicity included grade 3 infection in four patients. The present schedule of GDP showed modest efficacy and mild toxicity in patients with relapsed or refractory aggressive NHL.     

Rs1884444 variant in IL23R gene is associated with a decreased risk in esophageal cancer in Chinese population

Single nucleotide polymorphisms (SNPs) in interleukin‐23 receptor (IL23R) are involved in the pathogenesis of many cancers and autoimmune diseases. IL23R gene is still controversial in the study of esophageal cancer. The aim of this research is to investigate the influence of IL23R SNPs on the risk of esophageal cancer. Five hundred six esophageal cancer and 507 controls frequency matched by age and gender were conducted, and the genotypes were determined by the Agena MassARRAY. Logistic regression analysis was used to evaluate the odd ratios (ORs) and 95% confidence intervals (CIs) of rs1884444 and rs6682925 with susceptibility of esophageal cancer. A total of 30 articles are eligible. Pooled ORs and the 95% CI were calculated using the random‐effect model. Database predicts the expression of IL23R gene in esophageal cancer. IL23R rs1884444 allele G decreased the risk of esophageal cancer under allele, genotype, and additive models (allele model: OR = 0.82, 95% CI: 0.68‐0.98, P = .032; genotype model: OR = 0.65, 95% CI: 0.44‐0.97, P = .035; additive model: OR = 0.82, 95% CI: 0.68‐0.98, P = .031). Meta‐analysis shown that IL23R rs1884444 increased the risk of overall disease in allele model (OR = 1.16, 95% CI: 1.08‐1.25, P < .001), and also increased the risk of gastrointestinal tumor (OR = 1.18, 95% CI: 1.05‐1.31, P = .005). The database analysis showed that the expression of IL23R gene was upregulated in esophageal cancer tissues. IL23R rs1884444 may play an important role in the susceptibility of esophageal cancer.     

The association of c.1471G>A genetic polymorphism in XRCC1 gene with lung cancer susceptibility in Chinese Han population

Lung cancer is one of the most spread cancers in the world. The X-ray repair cross-complementing group 1 (XRCC1) gene plays an important role in the development of lung cancer. The objective of this study is to investigate the potential association of XRCC1 genetic polymorphisms with the susceptibility to lung cancer. In totally, 361 lung cancer patients (male, 276; female, 85; mean age, 62.55) and 361 cancer-free controls (male, 253; female, 108; mean age, 61.33) were enrolled in this case–control study. The genotypes of XRCC1 c.1471G>A genetic polymorphism were determined by the created restriction site–polymerase chain reaction (CRS-PCR) and DNA sequencing methods. The influence of XRCC1 gene on the susceptibility to lung cancer was analyzed by the analyses association. Our data indicated that significant differences were found in the frequencies of allelic and genotypic between lung cancer patients and cancer-free controls. The c.1471G>A genetic polymorphism was statistically associated with increased susceptibility to lung cancer [AA vs. GG: odds ratio (OR)?=?2.75, 95 % confidence interval (CI)?=?1.55–4.88, P?<?0.001; AA vs. GA/GG: OR?=?2.69, 95 % CI?=?1.55–4.69, P?<?0.001; A vs. G: OR?=?1.37, 95 % CI?=?1.09–1.71, P?=?0.007]. The allele A and genotype AA may contribute to the susceptibility to lung cancer. Taken together, these results showed that the functional c.1471G>A genetic polymorphism of XRCC1 was associated with lung cancer susceptibility in the studied population.     

Genetic variant of PRKAA1 and gastric cancer risk in an eastern Chinese population

Published data on the association between PRKAA1 rs13361707 T > C polymorphism and gastric cancer (GCa) susceptibility were inconclusive. To derive a more precise estimation of the association, we conducted a large-scale GCa study of 1,124 cases and 1,194 controls to confirm this association in an Eastern Chinese population. Our results showed that the C allele of PRKAA1 rs13361707 increased the GC risk in the study population [CT vs. TT, odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.40–2.12; CC vs. TT, OR = 2.15, 95%CI = 1.70–2.71; CT/CC vs. TT, OR = 1.86, 95%CI = 1.53–2.26; CC vs.TT/CT, OR = 1.49, 95%CI = 1.24–1.79]. In addition, the association of C allele with an increased GCa risk was still significant in subgroups, when stratified by age, sex, tumor site, drinking and smoking status. Moreover, the findings in the present study were validated by our further meta-analysis. In summary, these results indicated that the C allele of PRKAA1 rs13361707 was a low-penetrate risk factor for GCa.     

Int7G24A variant of transforming growth factor-beta receptor 1 is associated with osteosarcoma susceptibility in a Chinese population

The TGF-beta signaling pathway is important in the development and invasion of cancers. Int7G24A is an intronic variant of TGF-beta receptor type 1 and has been shown to be associated with the occurrence of some kinds of cancers. Nevertheless, the association of this polymorphism with osteosarcoma is unknown. In this study, we evaluated Int7G24A variant frequencies in osteosarcoma cases. The case–control study involved 168 osteosarcoma patients and 168 age- and gender-matched controls. The blood samples were obtained, and Int7G24A variant was determined by PCR amplification and DNA sequencing. The odds ratio (OR) and 95% confidence interval (95% CI) for the Int7G24A polymorphism were calculated using unconditional logistic regression adjusted for age and gender. Three analysis models, which are the dominant model, additive model and recessive model, were used to analyze the contribution of Int7G24A variant to osteosarcoma susceptibility. Heterozygotic and homozygotic Int7G24A variants were 33.93 and 6.55% in total 168 cases, while they were 28.57 and 2.98%, respectively, in total 168 controls. The ORs for homozygosity and heterozygosity of Int7G24A allele were 1.56 [95% CI, 0.98–1.83] and 2.89 [95% CI, 1.46–4.92] in additive model. The ORs of Int7G24A genotypes in dominant model and in recessive model were 1.75 [95% CI, 1.21–2.68] and 2.21 [95% CI, 1.34–4.72], respectively. There were significant increases in Int7G24A variants in osteosarcoma cases when compared to control in every three models. Further analysis showed that Int7G24A genotypes were not associated with gender and osteosarcoma location of the cases. However, Int7G24A was significantly increased in the cases less than 20 years old. Moreover, Int7G24A was significantly associated with increased distant metastasis of osteosarcoma. It is concluded that Int7G24A is a polymorphism of TGFBR1 that is associated with the susceptibility and distant metastasis of osteosarcoma.     

A RAD52 genetic variant located in a miRNA binding site is associated with glioma risk in Han Chinese

As a crucial homologous recombination repair gene, RAD52 participates in maintenance of genomic stability and prevention of tumorigenesis. Although several cancer susceptibility RAD52 single nucleotide polymorphisms (SNPs) have been identified previously, little was known on how the RAD52 SNPs are involved in glioma development in Han Chinese. Therefore, we examined the association between five RAD52 SNPs (rs1051669, rs10774474, rs11571378, rs7963551 and rs6489769) and glioma risk using a case–control design. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by logistic regression. We found that only the RAD52 rs7963551 SNP was significantly associated with glioma risk, with the odds of having the rs7963551 AC or CC genotype in patients was 0.49 (95 % CI 0.37–0.65, P = 9.2 × 10^?6) or 0.39 (95 % CI 0.18–0.81, P = 0.012) compared with the AA genotype. These data are consistent with functional relevance of allelic regulation of RAD52 expression by the rs7963551 SNP and miRNA let-7 in cancer cells. Stratified analyses elucidated that statistically significant association between glioma and rs7963551 SNP only existed in either astrocytic tumors (P = 6.3 × 10^?6) or oligoastrocytic tumors (P = 0.002). In conclusion, our results support the hypothesis that genetic variants influencing miRNA-mediated regulation of tumor suppressor genes or oncogenes may contribute glioma susceptibility.     

Association between glutathione S-transferase M1 null variant and risk of bladder cancer in Chinese Han population

Glutathione S-transferase M1 (GSTM1) is one of the most important families of phase II isoenzymes known to detoxify a variety of electrophilic compounds and carcinogens. The GSTM1 null variant is associated with decreased enzyme activity, and it has been assumed to be associated with bladder cancer. The association between the GSTM1 null variant and bladder cancer in the Chinese Han population was unclear owing to the obvious inconsistency from published studies. To quantify the association between the GSTM1 null variant and bladder cancer in the Chinese Han population, we carried out the meta-analysis. We estimated the pooled odds ratio (OR) with its 95 % confidence interval (95 % CI) to assess the association. Eight studies with a total of 3,887 individuals were finally included into the meta-analysis. Overall, there was an obvious association between the GSTM1 null variant and risk of bladder cancer in the Chinese Han population (OR?=?1.61, 95 % CI 1.41–1.84, P?<?0.001). There was no heterogeneity across those eight studies (I ²?=?0 %). The cumulative meta-analyses showed a trend of more obvious association between the GSTM1 null variant and risk of bladder cancer in the Chinese Han population as data accumulated by year. There was no obvious evidence of publication bias in the meta-analysis. In conclusion, the GSTM1 null variant is significantly associated with risk of bladder cancer in the Chinese Han population.     

A genetic variation in APE1 is associated with gastric cancer survival in a Chinese population

Altered DNA repair can be associated with aggressive tumor biology and impact on survival of cancer patients. We investigated whether genetic variation of human apurinic/apyrimidinic (AP) endonuclease, a key multifunctional gene involved in the base excision repair pathway, would play a role in gastric cancer survival outcomes. We genotyped APE1 rs1760944 by the TaqMan method in 925 gastric cancer patients. Analyses of association between the polymorphism and survival outcomes were carried out using the Kaplan-Meier method, Cox proportional hazards models, and the log-rank test. Survival analyses for all patients showed that the differences in median survival time between gastric cancer carriers with APE1 rs1760944 TT (55 months) and those with GT/GG (78 months), were statistically significant (P = 0.025, log-rank test). Kaplan-Meier survival estimates revealed that gastric cancer patients carrying the GT/GG genotypes had a higher survival than TT, and this protective effect was also more pronounced among subgroups with tumor size >5 cm (hazard ratio = 0.66, 95% confidence interval = 0.49-0.88), diffuse-type gastric cancer (0.76, 0.60-0.97), T3 depth of invasion (0.73, 0.57-0.93), lymph node metastasis (0.73, 0.58-0.92), no distant metastasis (0.81, 0.66-0.99), and TNM stage III and IV (0.75, 0.58-0.99 for stage III; 0.50, 0.29-0.88 for stage IV). Our results showed that the genetic variant rs1760944 in APE1 was associated with gastric cancer survival in a Chinese population. Larger studies are needed to verify our findings in different populations.     

Interleukin-1B gene promoter variants are associated with an increased risk of gastric cancer in a Chinese population

Studies suggest that IL-1beta (encoded by IL-1B gene) is a pro-inflammatory cytokine and potent inhibitor of gastric acid secretion, which is proposed as a key determinant in gastric carcinogenesis. Two potentially functional polymorphisms (C-31T and T-511C) in the IL-1B promoter were suggested to be correlated with alteration of Helicobacter pylori infection and IL-1beta expression and therefore may be associated with risk of gastric cancer. To test the hypothesis that these two polymorphisms are associated with gastric cancer risk, we performed a case-control study of 280 histologically confirmed gastric cancer patients and 258 age, sex frequency-matched cancer-free controls in a Chinese population. Multivariate logistic regression analyses revealed that the risks (adjusted odds ratio [OR] and 95% confidence interval [CI]) associated with the IL-1B variant genotypes were 1.64 (95% CI, 1.01-2.66) for -31TT and 1.52 (95% CI, 0.91-2.54) for -511CC, respectively, compared with their wild-type homozygotes. The risks were significantly more evident in individuals with H. pylori infection (adjusted OR, 2.14; 95% CI, 1.13-4.06 for -31TT; adjusted OR, 2.00; 95% CI, 1.02-3.89 for -511CC), which was consistent with the biological effects of IL-1beta. When we used the haplotype analyses and assumed the IL-1B -31T and -511C as risk alleles, no synergistic effect was found between these two loci. These findings indicate that these two IL-1B promoter variants may contribute to the risk of developing gastric cancer in the Chinese population, especially in individuals with H. pylori infection.     

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.