There is conflicting data regarding the clinicopathological significance of the risk factors associated with Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC). To address this controversy, we performed a meta-analysis for the clinicopathological and molecular characteristics of EBVaGC. The relevant published studies were reviewed according to the defined selection criteria. The effect sizes of the outcome parameters were estimated by an odds ratio or a weighted mean difference. This meta-analysis included 48 studies that encompassed a total of 9738 patients. The frequency of EBVaGC was 8.8%, and EBVaGC was significantly associated with ethnicity. It was more predominant in men and in younger individuals. Interestingly, EBVaGC was more prevalent in Caucasian and Hispanic patients than in Asian ones. EBVaGC developed most often in the cardia and body, and it generally showed the diffuse histological type. EBV was highly prevalent in the patients with lymphoepithelial carcinoma. EBVaGC was closely associated with remnant cancer and a CpG island methylator-high status, but not with Helicobacter pylori infection, a TP53 expression, and p53 mutation. In addition, EBVaGC was not significantly associated with the depth of invasion, lymph node metastasis, or the clinical stage. The clinicopathological and molecular characteristics of EBVaGC are quite different from those of conventional gastric adenocarcinoma. However, further study is needed to determine the effect of EBV on the survival of EBVaGC patients.

To evaluate the association of germ-line polymorphisms of genes that may impact treatment outcome of platinum and fluorouracil combination chemotherapy in advanced gastric cancer (AGC).

X-ray repair cross-complementing group 1 (XRCC1), one of the >20 genes that participate in the base excision repair (BER) pathway, is thought to account for differences in lung cancer susceptibility. Our meta-analysis on 2861 cases (lung cancer patients) and 2783 controls from eight eligible studies in Chinese populations showed that for the XRCC1 Arg194Trp polymorphism, compared with the Arg/Arg homozygous genotype, the variant Arg/Trp and Trp/Trp genotypes combined was not associated with lung cancer risk (OR=1.06, 95% confidence interval [CI]=0.89-1.27) (Z=0.70, P=0.48), nor was Arg280His (OR=0.63, 95% CI=0.28-1.41) (Z=1.12, P=0.26); however, for the XRCC1 Arg399Gln polymorphism, the combination of variant Arg/Gln and Gln/Gln genotypes was borderline significantly associated with lung cancer risk (OR=1.16, 95% CI=1.00-1.36) (Z=1.90, P=0.06), compared with the Arg/Arg homozygous genotype. Therefore, in the eight published studies in Chinese populations, we found little evidence of an association between the combined variant genotypes of the XRCC1Arg399Gln polymorphism and the increased risk of lung cancer.

A meta-analysis was conducted to obtain a 'quantitative' estimate of the extent of genetic damage in mammalian somatic cells exposed to non-ionizing radiation emitted from extremely low frequency electro-magnetic fields (ELF-EMF) and to compare with that in unexposed control cells.

Recent studies suggested that JAK2V617F mutation is frequent in patients with splanchnic vein thrombosis (SVT) but not in patients with other venous thromboembolic events (VTE). However, whether screening for the JAK2V617F mutation in VTE patients is justified remains unclear. Therefore, we performed a systematic review to assess the frequency of JAK2 mutation in VTE patients and the role of JAK2V617F mutation in the diagnosis of myeloproliferative neoplasms. MEDLINE and EMBASE databases were searched. Two reviewers independently performed study selection and extracted study characteristics. Pooled odds ratios of case-control studies and weighted mean proportion of the prevalence of JAK2V617F mutation of uncontrolled series were calculated. Twenty-four studies involving 3123 patients were included. Mean prevalence of JAK2 mutation was 32.7% (95% confidence interval, 25.5%-35.9%) in SVT patients. JAK2 mutation was associated with increased risk of SVT (odds ratio, 53.98; 95% confidence interval, 13.10-222.45). Mean prevalence of JAK2 mutation in other VTE patients was low (range, 0.88%-2.57%). Presence of JAK2V617F mutation in SVT patients was associated with a subsequent diagnosis of myeloproliferative neoplasm in many patients. JAK2 mutation is strongly associated with SVT, and routine screening of JAK2 mutation appears to be indicated in these patients.

Breast cancers lacking the estrogen receptor (ER) can be distinguished from other breast cancers on the basis of poor prognosis, high grade, distinctive histopathology and unique molecular signatures. These features further distinguish estrogen receptor negative (ER-) tumor subtypes, but targeted therapy is currently limited to tumors over-expressing the ErbB2 receptor.

Published data on the association between MDM2 309 T/G polymorphism and lung cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of eight studies including 6063 cases and 6678 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with GG variant genotype in recessive model when all the eligible studies were pooled into the meta-analysis (OR=1.17; 95% CI=1.02-1.34; P(heterogeneity)=0.06). In the subgroup analysis by ethnicity, significantly increased risks were found among Asians for TG versus TT (OR=1.20; 95% CI=1.05-1.37; P(heterogeneity)=0.30), GG versus TT (OR = 1.34; 95% CI=1.01-1.79; P(heterogeneity)=0.03) and dominant model (OR=1.26; 95% CI=1.11-1.43; P(heterogeneity)=0.14). However, no significant associations were found in both Europeans and Africans for all genetic models. This meta-analysis suggests that the MDM2 309G allele is a low-penetrant risk factor for developing lung cancer in Asians.

Previous evidence implicates CYP1A1 and GSTM1 polymorphisms as risk factors for various cancers. A number of studies have been devoted to the association of CYP1A1 or GSTM1 polymorphism with susceptibility to laryngeal carcinoma, with the results inconsistent and inconclusive. The aim of the present study was to assess the possible associations of laryngeal cancer risk with CYP1A1 genetic variation and GSTM1 null genotype respectively.

We conducted a case-control analysis, a family-based population analysis, and a meta-analysis to assess the role of family history of cancer and kidney cancer in association with the risk of renal cell carcinoma (RCC). A total of 325 cases and 329 controls were identified from an ongoing case-control study of RCC. Study variables were assessed through 45-minute structured face-to-face interviews. In the case-control analysis, a family history of any cancer (in first-degree relatives) was associated with a nonsignificant 1.2-fold increase in RCC risk [95% confidence interval (95% CI), 0.8-1.6]. The risk increased to 1.7 and became significant when the relative was a sibling (95% CI, 1.1-2.5). A family history of kidney cancer (kidney cancer in first-degree relatives) was associated with a 4.3-fold significantly increased risk of RCC (95% CI, 1.6-11.9). The cases reported a total of 2,536 first-degree relatives of which 21 (0.8%) had kidney cancer, and the controls reported a total of 2,333 first-degree relatives of which 5 (0.2%) had kidney cancer (P=0.003). In the family-based population analysis, a family history of kidney cancer was associated with a 2.8-fold increased risk of RCC (95% CI, 1.0-7.8). The meta-analysis further confirmed this significant association with a 2.2-fold increased risk of RCC (95% CI, 1.6-2.9). To our knowledge, this is the first study to use three analytic strategies to investigate the association between a family history of kidney cancer and risk of RCC, and the first systematic evaluation of the relative risk for developing RCC associated with family history.

Lung cancer is the most common cancer worldwide. Polymorphisms in genes associated with carcinogen metabolism may modulate risk of disease. Glutathione S-transferase pi (GSTP1) detoxifies polycyclic aromatic hydrocarbons found in cigarette smoke and is the most highly expressed glutathione S-transferase in lung tissue. A polymorphism in the GSTP1 gene, an A-to-G transition in exon 5 (Ile105Val, 313A --> 313G), results in lower activity among individuals who carry the valine allele. The authors present a meta- and a pooled analysis of case-control studies that examined the association between this polymorphism in GSTP1 and lung cancer risk (27 studies, 8,322 cases and 8,844 controls and 15 studies, 4,282 cases and 5,032 controls, respectively). Overall, the meta-analysis found no significant association between lung cancer risk and the GSTP1 exon 5 polymorphism. In the pooled analysis, there was an overall association (odds ratio = 1.11, 95% confidence interval: 1.03, 1.21) between lung cancer and carriage of the GSTP1 Val/Val or Ile/Val genotype compared with those carrying the Ile/Ile genotype. Increased risk varied by histologic type in Asians. There appears to be evidence for interaction between amount of smoking, the GSTP1 exon 5 polymorphism, and risk of lung cancer in whites.

Although a number of studies have been conducted to address the relation between a gene deletion polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer, no definite conclusion has been reached and no clear risk pattern has yet to emerge for GSTM1. We first conducted case-control studies that included 1920 subjects using a genotyping method allowing the definition of GSTM1-null (-/-), homozygous wild-type (+/+), and heterozygous (+/-) genotypes. The results show that GSTM1(-/-) confers an increased risk for breast cancer development compared with that in GSTM1-present individuals (+/+ and +/-), which was subsequently confirmed by a meta-analysis of all of the 41 relevant studies (odds ratio: 1.10, P<0.001). Unexpectedly, we found that GSTM1(+/+) is also a risk genotype compared with GSTM1(+/-). Furthermore, we identified a functional polymorphism in the GSTM1 promoter region associated with breast cancer. The variant allele modifies DNA binding to the AP-2alpha transcription factor, resulting in reduced promoter activity and mRNA expression. However, this low-activity allele is associated with reduced breast cancer risk. It seems that approximately 60-70% expression from one allele of GSTM1 could suffice for protection against breast cancer; null activity and overactivity of GSTM1 are both disadvantageous. These results indicate a U-shaped association of GSTM1 with breast cancer, which challenges the linear gene-dosage effect of GSTM1 that was previously proposed. We recommend that a more complicated role for GSTM1 should be considered in breast cancer risk prediction.

Published data on the association between FAS -1,377 G/A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 studies including 10,564 cases and 12,075 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with AA variant genotype when all the eligible studies were pooled into the meta-analysis (for AA vs GG: OR = 1.19; 95% CI = 1.01-1.40; P (heterogeneity) = 0.05; for recessive model: OR = 1.21; 95% CI = 1.04-1.41; P (heterogeneity) = 0.05). In the subgroup analysis by ethnicity, borderline statistically significantly increased risks were found among Asians for recessive model (OR = 1.20; 95% CI = 1.00-1.45; P (heterogeneity) = 0.01). In the subgroup analysis by population-based controls or hospital-based controls, statistically significantly increased risks were found among groups with population-based controls for AA versus GG (OR = 1.27; 95% CI = 1.02-1.58; P (heterogeneity) = 0.05) and recessive model (OR = 1.25; 95% CI = 1.00-1.59; P (heterogeneity) = 0.01). For breast cancer, borderline statistically significantly increased risks were found for AA versus GG (OR = 1.29; 95% CI = 1.00-1.67; P (heterogeneity) = 0.41). In summary, this meta-analysis suggests that the FAS -1,377 G/A polymorphism is associated with cancer susceptibility.

Atypical protein kinase Ciota (PKCiota) is an oncogene in non-small cell lung cancer (NSCLC). Here, we identify four functional gene targets of PKCiota in lung adenocarcinoma (LAC), the most prominent form of NSCLC.

Published data regarding the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and prostate cancer risk have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR C677T and A1298C polymorphisms and prostate cancer risk. Six studies including 3511 cases and 2762 controls described C677T genotypes, among which four articles totalling 838 cases and 1121 controls described A1298C genotypes, were involved in this meta-analysis. Overall meta-analysis indicated that the 677T allele was more likely to exert a protective effect on prostate cancer risk (OR=0.81, 95% CI: 0.68-0.98) with a recessive genetic model. No association was found for the 677CT genotype and the 677TT mutant homozygote with prostate cancer risk compared with 677CC, with OR=1.13 (95% CI: 0.88-1.45) and OR=0.85 (95% CI: 0.71-1.03), respectively. No evidence of an association of MTHFR A1298C polymorphism with prostate cancer was found. This meta-analysis supports that the C677T of the MTHFR gene is a low-penetrance susceptibility gene for prostate cancer, and might provide protective effects against prostate cancer risk.

Although several studies have examined the association between phase I/II enzyme polymorphisms and esophageal adenocarcinoma (EAC) and/or Barrett's esophagus (BE), their overall findings remain unclear. We performed a systematic review and meta-analysis to determine whether phase I/II polymorphisms are independent risk factors for either BE or EAC. We employed keyword searches in multiple databases to identify studies published before October 1, 2007. Single-nucleotide polymorphisms (SNPs) examined in > or =3 studies were meta-analyzed to obtain a pooled estimate of effect. Meta-analysis suggested the minor allele for GSTP1 Val(105) conveys modest excess risk (odds ratio [OR](BE)= 1.50, 95% confidence interval [CI] 1.16-1.95; OR(EAC)= 1.20, 95% CI 0.94-1.54). No excess risk was observed with GSTM1 null (OR(BE)= 0.77, 95% CI: 0.56-1.08; OR(EAC)= 1.08, 95% CI: 0.79-1.48), GSTT1 null (OR(BE)= 1.35, 95% CI: 0.91-2.01; OR(EAC)= 0.84, 95% CI: 0.48-1.49), or CYP1A Val(462) (OR(EAC)= 0.89, 95% CI: 0.40-1.97). Insufficient data existed to meta-analyze remaining SNPs. Our review identified GSTP1(Ile105Val) as a possible risk factor for BE and EAC in Caucasian males. No excess risk was observed for other phase I/II polymorphisms with sufficient data to meta-analyze. Additional studies are needed to determine if GSTP1 conveys excess risk in females or non-Caucasians and to evaluate other phase I/II polymorphisms.

The genetic polymorphism of TP53 codon 72 is thought to have significant effect on lung cancer risk, but the results are inconsistent. In this meta-analysis, we assessed 23 published studies involving 15,857 subjects of the association between TP53 codon 72 polymorphism and risk of lung cancer. For the homozygote Pro/Pro and Pro allele carriers (Pro/Pro+Pro/Arg), the ORs for all studies combined (7495 cases and 8362 controls) were 1.221 (95% CI=1.046-1.425; P=0.021 for heterogeneity) and 1.148 (95% CI=1.040-1.266; P=0.008 for heterogeneity). In the stratified analysis by ethnicity, significantly increased risks were found in Asians (3254 cases and 3350 controls) for both the homozygote Pro/Pro (OR=1.395; 95% CI=1.206-1.613; P=0.806 for heterogeneity) and the Pro allele carriers (OR=1.109; 95% CI=1.000-1.228; P=0.458 for heterogeneity). In Caucasians (3359 cases and 3953 controls), significantly elevated risk was associated with Pro allele carriers (OR=1.180; 95% CI=1.029-1.353; P=0.073 for heterogeneity). In the subgroup analyses by pathological type, the ORs for the homozygote Pro/Pro and Pro allele carriers were 1.289 (95% CI=1.027-1.618; P=0.096 for heterogeneity) and 1.168 (95% CI=1.062-1.284; P=0.231 for heterogeneity) for lung adenocarcinoma (2724 cases and 6591 controls). When stratified by smoking status, the pooled OR was 1.440 (95% CI=1.078-1.923; P=0.042 for heterogeneity) for the Pro allele carriers among smokers (1480 cases and 1414 controls). Although some statistical bias could not be eliminated, this meta-analysis suggests that the Pro allele is a low-penetrant risk factor for developing lung cancer. Additionally, we found that this phenomenon was more prominent in subgroups such as in Asians and Caucasians, in lung adenocarcinoma, or in smokers.

FAS is a cell surface receptor involved in apoptotic signal transmission and plays important roles in the etiology of cancer. The -1377G>A and -670A>G polymorphisms of the FAS gene influence the FAS transcription and have been implicated in cancer risk. However, the results from the published studies on the association between these two FAS polymorphisms and cancer risk are conflicting. To derive a more precise estimation of association between the FAS polymorphisms and risk of cancer, we performed a meta-analysis of 11 461 cancer cases and 12 708 controls from 34 published case-control studies for these two polymorphisms. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the -1377AA genotype were associated with higher cancer risk than those with the -1377GG (OR = 1.21, 95% CI: 1.08-1.36, P(heterogeneity) = 0.062) or GA/GG (OR = 1.23, 95% CI: 1.10-1.36, P(heterogeneity) = 0.060) genotypes, whereas the -670GG genotype had no effects on overall cancer risk. In the stratified analyses for the -1377G>A polymorphism, there was a significantly increased risk of breast cancer but a significantly decreased risk of melanoma in a dominant model. Moreover, a significantly increased risk was observed among smokers in a recessive model (OR = 1.96, 95% CI: 1.55-2.49; P(heterogeneity) = 0.528). Although some modest bias could not be eliminated, this meta-analysis suggested that the FAS -1377A allele is a low-penetrant risk factor for cancer development, particularly among smokers.

Previous studies have implicated CYP1A1 and GSTM1 polymorphisms as risk factors for various cancers. A number of studies have been devoted to the association of CYP1A1 or GSTM1 polymorphism with susceptibility to oral carcinoma and have yielded conflicting results. The aim of the present study was to assess the possible associations of oral cancer risk with CYP1A1 genetic variation and GSTM1 null genotype respectively via systematic meta-analyses. The data suggest that variant genotypes of CYP1A1 might not be risk factors for oral cancer, whereas GSTM1 null genotype significantly increases susceptibility to oral cancer in Asians but not 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 Lauren's 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.

Several polymorphisms in the vitamin D receptor (VDR) gene have been reported to influence breast cancer risk. However, the published findings have been conflicting. We conducted a meta-analysis of 21 case-control studies with Fok1 (eight studies with 5,284 cases and 7,500 controls), Bsm1 (14 studies with 5,498 cases and 7,943 controls), Apa1 (four studies with 1,138 cases and 7,943 controls), Taq1 (10 studies with 4,459 cases and 5,485 controls) polymorphisms. The results showed Fok1 polymorphism was associated with an overall significantly increased risk of breast cancer (ff vs. FF: OR = 1.15, 95% CI = 1.03-1.28; the recessive model ff vs. Ff + FF: OR = 1.14, 95% CI = 1.03-1.26). In subgroup analysis, a significant association was evident between Fok1 polymorphism and breast cancer in European population (ff vs. FF: OR = 1.16, 95% CI = 1.04-1.30; the recessive model ff vs. Ff + FF: OR = 1.15, 95% CI = 1.04-1.28). There was no between-study heterogeneity in any of these analyses. No significant associations were observed between the Bsm1, Apa1 and Taq1 variants and breast cancer risk. So, the current meta-analysis shows that Fok1 may be a susceptibility biomarker for breast cancer especially in European population.