Wen Zhuang

P53 codon 72 polymorphism and gastric cancer: A meta-analysis of the literature

Studies investigating the association between p53 codon 72 polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta‐analysis included 12 case‐control studies, which included 1,665 gastric cancer cases and 2,358 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [Arg/Arg odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.79, 1.16; Pro/Pro (OR = 1.21, 95% CI = 0.92, 1.58); Pro/Arg (OR = 0.95, 95% CI = 0.79, 1.14)] between gastric cancer and noncancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly lower frequency of Arg/Arg (OR = 0.84, 95% CI = 0.72, 0.99) than noncancer patients among Asians. Stratified the various studies by the location, stage, Laurens classification, and histological differentiation of gastric cancer, we found that (i) patients with cardia gastric cancer had a significantly higher frequency of Pro/Pro (OR = 3.20, 95% CI = 1.46,7.01) than those with noncardia gastric cancer among Asians; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/Arg (OR = 1.48, 95% CI = 1.01, 2.16) than those with early (stage I/II) gastric cancer among Asians; (iii) patients with poor differentiation had a significantly lower frequency of Pro/Pro (OR = 0.13, 95% CI = 0.03, 0.64) than those with well differentiation among Caucasians. This meta‐analysis suggests that the p53 codon 72 polymorphism may be associated with gastric cancer among Asians, and that difference in genotype distribution may be associated with the location, stage, and histological differentiation of gastric cancer.

Consumption of Large Amounts of Allium Vegetables Reduces Risk for Gastric Cancer in a Meta-analysis

BACKGROUND & AIMS The chemopreventive effects of Allium vegetables (onions, garlic, shallots, leeks, chives, and so forth) have been studied extensively, although their effect on gastric cancer risk is controversial. We performed a meta-analysis of cohort and case-control studies to analyze this association. METHODS We searched MEDLINE for studies of Allium vegetable consumption and gastric cancer that were published in any language, from January 1, 1966, to September 1, 2010. We analyzed 19 case-control and 2 cohort studies, of 543,220 subjects. We pooled the relative risks from individual studies using a random-effects model and performed dose-response, heterogeneity, and publication bias analyses. RESULTS In a pooled analysis of all studies, consumption of large amounts of Allium vegetables (in a comparison of the highest and lowest consumption groups) reduced the risk for gastric cancer (odds ratio, 0.54; 95% confidence interval, 0.43-0.65). Specific analyses for onion, garlic, leek, Chinese chive, scallion, garlic stalk, and Welsh onion yielded similar results, except for onion leaf. The estimated summary odds ratio for an increment of 20 g/day of Allium vegetables consumed (approximately the average weight of 1 garlic bulb) was 0.91 (95% confidence interval, 0.88-0.94), based on case-control studies from the dose-response meta-analysis. CONCLUSIONS In a meta-analysis, consumption of high levels of Allium vegetables reduced the risk for gastric cancer risk. Because of potential confounding factors and exposure misclassification, further studies are required to establish this association.

Interleukin-10 -1082 promoter polymorphism associated with gastric cancer among Asians

Studies investigating the association between interleukin-10 (IL-10) -1082 promoter polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarise the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 13 case-control studies, which included 2227 gastric cancer cases and 3538 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [AA odds ratio (OR)=0.92, 95% confidence interval (CI)=0.73, 1.14; AG (OR=1.09, 95% CI=0.87, 1.36); GG (OR=1.03, 95% CI=0.85, 1.25)] between gastric cancer and noncancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly lower frequency of AA (OR=0.71, 95% CI=0.52, 0.97) and higher frequency AG (OR=1.53, 95% CI=1.15, 2.03) than noncancer patients among Asians. When stratifying by the location of gastric cancer, we found that patients with cardia gastric cancer had a significantly lower frequency of AA (OR=0.53, 95% CI=0.34, 0.83) and higher frequency AG (OR=1.50, 95% CI=1.06, 2.11) than those with noncardia gastric cancer among Caucasians. When stratifying by the Laurens classification of gastric cancer, we observed no statistically significant differences in genotype distribution. This meta-analysis suggests that the IL-10 -1082 promoter polymorphism may be associated with gastric cancer among Asians, and that differences in genotype distribution may be associated with the location of gastric cancer.

Interleukin-8 -251 A/T gene polymorphism and gastric cancer susceptibility: a meta-analysis of epidemiological studies.

Previous studies suggested the relationship between interleukin (IL)-8 -251 A/T gene polymorphism and risk of gastric cancer (GC). However, the currently available results were not consistent. The present study aimed to quantitatively analyse this association using a meta-analysis. Published literature from PubMed, EMBASE and CNKI (China Knowledge Resource Integrated Database) were retrieved. Twelve case-control studies with 3012 cases of GC and 3893 controls were included. Overall, IL-8 -251 A/T polymorphism was not associated with the risk of GC. However, when stratified for ethnicity/country, the results showed that A allele carriers had an increased risk of GC while T allele carriers had a decreased risk of GC in Korean people. When stratified for Helicobacter pylori infection, the results showed that A allele carriers with H. pylori infection had an increased risk of GC while T allele carriers with or without H. pylori infection had a decreased risk of GC. When stratified for tumor location and histological type (Laurens classification), A allele carriers had an increased risk of intestinal- and diffuse-type of GC and non-cardia cancer, while T allele carriers had a decreased risk of intestinal- and diffuse-type of GC and non-cardia cancer. These results suggest that overall IL-8 -251 A/T gene polymorphism is not associated with the risk of GC and the association may be varied according to histological type, tumor location, H. pylori infection and ethnicity/country. More well-designed studies based on larger population are needed to confirm our results and further evaluate the association between IL-8 -251 A/T gene polymorphism and gastric cancer.

Is dietary fat associated with the risk of colorectal cancer? A meta-analysis of 13 prospective cohort studies

BackgroundThe results of animal studies suggest there is a significant role for dietary fat in the development of colorectal cancer (CRC). However, inconsistent results have been reported by epidemiological studies.Aim of studyTo evaluate the association between total dietary fat and risk of colorectal cancer development using a meta-analysis based on prospective cohort studies.MethodsPublished literature was retrieved from Medline, Embase and CNKI (China Knowledge Resource Integrated Database) databases updated to 1st May, 2009. Overall, thirteen prospective cohort studies with 3,635 cases and 459,910 participants were included.ResultsThe combined relative risk (RR) [95% confidence interval (95%CI)] for the risk of CRC was 0.99 (0.89,1.09) when the highest level of total dietary fat was versus (vs.) the lowest level. Stratified analyses according to gender, ethnicity, country and age showed that the highest level of total dietary fat did not increase the risk of CRC [RR (95%CI): 0.89 (0.77,1.03) for males; 1.09 (0.94,1.26) for females; 1.08 (0.94,1.25) for Caucasians; 0.90 (0.77,1.04) for Asians; 1.13 (0.94,1.36) for Americans; 0.92 (0.81,1.04) for individuals older than 40]. Besides those, the highest level of total fat diet also did not increase the risk of neither colon cancer [RR (95%CI): 0.96 (0.82,1.13)] nor rectal cancer [RR (95%CI):1.07 (0.63,1.82)]. Furthermore, neither animal fat nor plant fat were associated with the risk of CRC [RR (95%CI): 1.05 (0.91–1.22) for animal fat and 0.96 (0.82–1.11) for plant fat].ConclusionsThis meta-analysis suggests that dietary fat may not be associated with the increased risk of CRC. More well-designed studies with larger population performed among Asians are needed to further evaluate the associations. In addition, probable bias caused by measurement error should be noticed in this meta-analysis, and measurement error needs to be adjusted in the future studies.

Vascular endothelial growth factor (VEGF) gene polymorphisms and gastric cancer risk in a Chinese Han population

The association between vascular endothelial growth factor (VEGF) gene polymorphisms and gastric cancer risk is still controversial and ambiguous. The objective of this study was to investigate the association between VEGF gene polymorphisms and gastric cancer risk in Chinese Han patients. We extracted the peripheral blood samples in 150 patients with gastric cancer and 150 controls. Polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) analysis was performed to detect three VEGF gene polymorphisms (−634 G/C, +936 C/T, and +1612 G/A) in these patients. Patients with gastric cancer had a significantly higher frequency of 1612 AA genotype (OR = 6.26, 95% CI = 1.80, 21.85; P = 0.004) than controls. Patients with cardia gastric cancer had a significantly lower frequency of AA (OR = 0.11, 95% CI = 0.01, 0.89; P = 0.04) than those with noncardia gastric cancer. Patients with Laurens diffuse‐type gastric cancer had a significantly higher frequency of AA (OR = 3.41, 95% CI = 1.22, 9.55; P = 0.02) than those with Laurens intestinal‐type gastric cancer. The −634 G/C and +936 C/T gene polymorphisms were not associated with a risk of GC and its progression. This study suggests that the VEGF +1612 G/A gene polymorphisms may be associated with gastric cancer in Chinese Han patients, and that difference in genotype distribution may be associated with the location and Laurens classification of gastric cancer. Mol. Carcinog.

Glutathione S-transferase P1 gene polymorphism associated with gastric cancer among Caucasians

Studies investigating the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarise the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 10 case-control studies, which included 1161 gastric cancer cases and 2847 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [AA odds ratio (OR)=1.14, 95% confidence interval (CI)=0.91, 1.44; AG (OR=0.82, 95% CI=0.66, 1.03); GG (OR=1.11, 95% CI=0.55, 2.24)] between gastric cancer and non-cancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly higher frequency of AA (OR=1.53, 95% CI=1.14, 2.06) and lower frequency of AG (OR=0.70, 95% CI=0.55, 0.89) than non-cancer patients among Caucasians. When stratifying by the location and Laurens classification of gastric cancer, we observed no statistically significant differences in genotype distribution. This meta-analysis suggests that the GSTP1 codon 105 polymorphism may be associated with gastric cancer among Caucasians.

Vascular endothelial growth factor (VEGF) +936 C/T gene polymorphisms and gastric cancer risk: a meta-analysis involving 4,138 subjects.

The association between vascular endothelial growth factor (VEGF) +936 C/T gene polymorphisms and gastric cancer risk is still controversial and ambiguous. The objective of our study was to investigate this association. The Medline and Embase databases were searched by two investigators. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to test the association between VEGF +936 C/T polymorphisms and gastric cancer risk. Our meta-analysis comprised seven case-control studies, which included 1,893 gastric cancer cases and 2,245 controls. The combined results showed that there was no relationship between VEGF +936 C/T gene polymorphisms and gastric cancer risk (cc: OR 0.97, 95% CI 0.85, 1.11; CT: OR 1.01, 95% CI 0.88, 1.16; TT: OR 1.10, 95% CI 0.79, 1.55). Subgroup analysis by ethnicity and stage, location, and Lauren classification of gastric cancer did not change the results. This meta-analysis suggests that there is no association between VEGF +936 C/T polymorphisms and gastric cancer risk. Further studies should pay attention to other potentially functional SNPs.

Polymorphisms of Thymidylate Synthase in the 5′- and 3′-Untranslated Regions and Gastric Cancer

Studies investigating the association of polymorphisms in the 5′-untranslated regions (5′UTR) and 3′-untranslated regions (3′UTR) of thymidylate synthase with gastric cancer susceptibility and sensitivity to fluoropyrimidine-based chemotherapy report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. This meta-analysis included ten studies, which included 1,730 gastric cancer cases and 1,843 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution of 5′UTR or 3′UTR between gastric cancer and noncancer patients. When stratifying for race, we found that: (1) among Asians, patients with gastric cancer had significantly higher frequency of 2R/2R of 5′UTR than did noncancer patients, and (2) among Caucasians, patients with gastric cancer had significantly lower frequency of ins6/ins6 and higher frequency of ins6/del6 of 3′UTR than did noncancer patients. No significantly different response rate or survival of gastric cancer with fluoropyrimidine-based chemotherapy were observed with genotype distribution of 5′UTR or 3′UTR among Caucasians or Asians. This meta-analysis suggests that polymorphisms in the 5′UTR and 3′UTR of thymidylate synthase may be associated with gastric cancer susceptibility, but are not correlated with sensitivity of gastric cancer to fluoropyrimidine-based chemotherapy.

Adjuvant imatinib for patients with high-risk gastrointestinal stromal tumors: a retrospective cohort study

The duration of adjuvant imatinib for high-risk patients with gastrointestinal stromal tumors (GISTs) is still controversial. Therefore, we retrospectively analyzed the data of high-risk patients with GISTs to investigate the appropriate duration. All 185 patients were divided into 4 groups: <1 year (Group A), 1–2 years (Group B), 2–3 years (Group C) and >3 years (Group D). The mean recurrence-free survival (RFS) in Groups A, B, and C were 44.3, 62.1, and 86.8 months, respectively (P < 0.001); the mean overall survival (OS) in Groups A, B and C was 75.2, 88.1, and 94.7 months, respectively (P = 0.009). The 5-year RFS in Groups A, B, C, and D was 15%, 26%, 83%, and 100%, respectively (P < 0.001); and the 5-year OS was 64%, 88%, 88%, and 100%, respectively (P < 0.001). The greatest impact on unfavorable outcomes was the tumor mitotic rate (HR, 2.01, 95% CI, 1.38–2.94; P < 0.001). Duration of adjuvant imatinib was the only favorable factor (HR, −0.95, 95% CI, 0.93–0.97; P < 0.001). For high-risk patients with high tumor size or mitotic rate, or non-gastric GISTs, we recommend that more than 3 years of adjuvant imatinib is feasible.