To evaluate the association between xeroderma pigmentosum group D (XPD), genetic polymorphism Lys751Gln and esophageal cancer risk.

To evaluate the association of human leukocyte antigen (HLA)-DQB1 alleles with hepatocellular carcinoma (HCC) through meta-analysis of published data.

Pancreatic cancer was the fourth leading cause of cancer death in the United States in 2010. Recurrence of disease after resection occurs because of neoplastic cell survival. To better understand these highly aggressive cells, gene expression microarrays were performed.

The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer.

Glutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens.

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. Common genetic variants (single nucleotide polymorphisms, SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences. Until now, several studies had evaluated the association between the polymorphisms in the hsa-miR-196a2 rs11614913 and cancer risk in diverse populations and in multiple types of cancer, with contradictory outcomes. Therefore, here we performed a meta-analysis to address the association between this polymorphism and cancer risk. A total of nine studies involving 6,540 cases and 7,562 controls were retrieved based on PubMed. Our analysis demonstrated that hsa-miR-196a2 rs11614913 CC genotype significantly increased the cancer risk in homozygote comparison model compared to TT genotype (OR=1.18; 95% CI, 1.01-1.68). Moreover, significant association of this polymorphism with breast cancer was found based on homozygote comparison model (OR=1.30; 95% CI, 1.01-1.26) and dominant model (OR=1.11; 95% CI, 1.01-1.23). In addition, hsa-miR-196a2 rs11614913 CC genotype was significantly associated with cancer risk in Chinese and Indian (OR=1.21; 95% CI, 1.05-1.40), but not in Caucasians (OR=1.03; 95% CI, 0.89-1.19). Taken together, our results indicate that the polymorphism of hsa-miR-196a2 rs11614913 is associated with cancer susceptibility, especially with breast cancer and in Chinese and Indian populations.

The relationship of stomach cancer susceptibility and the presence of E-cadherin (CDH1) promoter -160 C/A polymorphism had been reported with conflicting results. To further explore the association of this polymorphism with stomach cancer susceptibility, we performed an extensive search of relevant studies and carried out a meta-analysis to obtain a more precise estimate. A total of 16 studies including 2,611 cases and 3,788 controls were involved in this meta-analysis. When all studies involved, the meta-analysis results suggest no statistically significant association between CDH1 -160 C/A polymorphism and stomach cancer risk (CA vs. CC: OR = 1.01, 95% CI: 0.85-1.19; AA vs. CC: OR = 1.05, 95% CI: 0.75-1.46; dominant model: OR = 1.02, 95% CI: 0.86-1.20; recessive model: OR = 1.04, 95% CI: 0.76-1.41). When subgroup analyses were performed by ethnicity, the A-allele carriers conferred a decreased stomach cancer risk in Asians (AA vs. CC: OR = 0.67, 95% CI: 0.47-0.96; dominant model: OR = 0.85, 95% CI: 0.72-0.99), but no statistically significant association was found in Caucasians. In conclusion, this meta-analysis suggests that CDH1 -160 A-allele may play a protective role of stomach cancer development in Asians but not in Caucasians.

To examine the association between fibroblast growth factor receptor-4 (FGFR-4) genetic polymorphisms (Gly-388Arg) and prostate cancer susceptibility.

The latest data show that breast, prostate, lung and colorectal cancer are the four most frequent cancers in both sexes worldwide. A number of molecular epidemiological studies have been conducted to examine the association between TNF alpha -308G/A and the risk of those cancers. However the results have been inconclusive or inconsistent. We then performed a meta-analysis to derive a precise estimation of this association. We carried out a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database for studies using related keywords. The inclusion criteria were (i) in English or Chinese; (ii) case-control study on this association; (iii) provide usable genotype frequencies; and (iv) sufficient published data for estimating an odds ratio (OR) with 95% confidence interval (CI). ORs and 95% CIs were calculated to assess the strength of this association under homozygote comparison (AA vs GG), heterozygote comparison (GA vs GG), dominant (AA/GA vs GG) and recessive (AA vs GA/GG) genetic model comparison. Thirty case-control studies with a total number of 16,507 cases and 19,749 controls were selected for analysis. Overall, no significant association was found between this polymorphism and the risk of total four cancers (GA vs GG: OR=1.02, 95% CI=0.91-1.14, P=0.78). However, there was a significant association between this polymorphism and breast cancer risk in western populations (GA vs GG: OR=0.91, 95% CI=0.85-0.96, P=0.002). This meta-analysis also revealed that this polymorphism was not associated with susceptibility to the other three cancers.

The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP) at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory.

P73 is a structural and functional homologue of p53, and plays an important role in regulating cell cycle and apoptosis. A potentially functional polymorphism (designated as p73 G4C14-to-A4T14) has been identified in a region in exon 2 of the p73 gene, which may theoretically form a stem-loop structure and thereby affect p73 expression. Several investigations have reported the correlation between p73 G4C14-to-A4T14 polymorphism and cancer risk. However, the results are inconclusive. To further assess the association between p73 polymorphism and cancer risk, we performed meta-analysis of the data sets obtained from 26 individual studies involving 8,148 cancer patients and 8,150 controls. The association between p73 G4C14-to-A4T14 polymorphism and cancer risk was determined by crude odd ratios (OR) with 95% CI (confidential interval). AT-allele carriers were found to have a significantly increased risk of cervical cancer (AT/GC vs. GC/GC, OR = 1.63, 95% CI = 1.14-2.33; AT/AT + AT/GC vs. GC/GC, OR = 1.49, 95% CI = 1.05-2.10), colorectal cancer (AT/AT vs. AT/GC + GC/GC, OR = 1.98, 95% CI = 1.25-3.12), head and neck cancer (AT/AT + AT/GC vs. GC/GC, OR = 1.44, 95% CI = 1.06-1.96) and other cancers (AT/AT vs. GC/GC, OR = 1.78, 95% CI = 1.24-2.57; AT/AT vs. AT/GC + GC/GC, OR = 1.80, 95% CI = 1.26-2.56). In the stratified analysis of ethnicity, a significantly elevated cancer risk was found in Caucasians (AT/AT + AT/GC vs. GC/GC, OR = 1.18, 95% CI = 1.08-1.30; allele AT vs. allele GC, OR = 1.15, 95% CI = 1.06-1.24). No significant association of p73 polymorphism with the cancer risk of smoking was detected by stratified analysis by smoking status. Together, our data suggest that the p73 G4C14-to-A4T14 may be a risk factor of cancer especially in Caucasians.

The association of the two ERCC polymorphisms, Asp312Asn and Lys751Gln, with lung cancer risk remains controversial and inconclusive. To better evaluate the potential role of the two polymorphisms and interaction with tobacco smoking in lung cancer susceptibility presented in diverse populations, we have conducted a meta-analysis based on 26 studies from 24 publications which included analyses of Asp312Asn (7121 cases, 8962 controls) and Lys751Gln (8396 cases, 10510 controls) polymorphisms. Overall, significantly elevated lung cancer risk was associated with ERCC2 312Asn allele(homozygous model: OR=1.20[1.05-1.36], P=0.006; recessive model: OR=1.20[1.06-1.35], P=0.004) and 751Gln allele(homozygous model: OR=1.31[1.17-1.46], P<0.00001; heterozygous model: OR=1.11[1.04-1.19], P=0.003; recessive model: OR=1.23[1.11-1.37], P<0.0001; dominant model: OR=1.15[1.08-1.23], P<0.0001). In ethnic subgroup analyses, significantly increased risk was associated with ERCC2 312Asn allele for both Caucasians and Asians, and 751Gln allele for both Caucasians and Latino-Americans. When stratified by smoking status, significantly elevated risk of both polymorphisms for never-smokers was detected (dominant model, OR=1.46[1.09-1.95] and 1.57[1.19-2.08], P=0.01 and 0.002, respectively). In conclusion, this meta-analysis suggests that the two ERCC2 polymorphisms may contribute to lung cancer susceptibility serving as low-penetrance risk factors. Extremely large-scale evidence would be necessary to confirm the effects on ethnically specific populations and gene-environment interactions.

We explored the role of the C-160A single-nucleotide polymorphism (SNP) of CDH1 in susceptibility to gastric cancer through a systematic review and meta-analysis. Fourteen studies were included, the original groups collapsed, and re-grouped in accordance with the most appropriate genetic model. Potential sources of heterogeneity were sought out via subgroup analyses and sensitivity analyses, and publication biases were estimated. No significant association of C-160A was found with the overall risk of developing gastric cancer, but the apparently opposite tendency was noted between Caucasians and Asians, and a statistically significant association was found among Asians. The seemingly opposite tendency of associations was also seen between noncardia and cardia types or between sporadic diffuse and intestinal types of gastric cancer, but no statistically significant findings were noted. Genotyping techniques, sample size, quality appraisal scores, or article publication time did not constitute the source of heterogeneity across studies; and no publication biases were found in our meta-analysis.

Case-control studies on the association between XPA A23G and lung cancer have provided either controversial or inconclusive results. To clarify the effect of XPA A23G on the risk of lung cancer, a meta-analysis of all case-control observational studies was performed. Pooled odds ratios (ORs) for various polymorphisms were estimated using random and fixed effects models. The Q-statistic was used to evaluate the homogeneity, and Egger and Begg tests were used to assess publication bias. For the homozygote GG and G allele carriers (GA + GG), the pooled ORs were 1.24 (95% CI 1.05-1.46; P = 0.27 for heterogeneity) and 1.30 (95% CI 1.13-1.51; P = 0.45 for heterogeneity) compared to the homozygous genotype (AA). In the stratified analysis by ethnicity, the ORs of the G allele carriers and the homozygote GG were 1.28 (95% CI 1.10-1.49; P = 0.07 for heterogeneity) and 1.42 (95% CI 1.04-1.93; P = 0.39 for heterogeneity) among non-Caucasians. No significant associations were found in the Caucasian population in any of the genetic models. When studies that were not in Hardy-Weinberg equilibrium (HWE) were corrected, the pattern of the results remained the same. Our results indicated a significantly decreased risk of lung cancer in non-Caucasians with the G allele.

This study aimed to perform a meta-analysis to assess the association of survivin -31 G/C promoter polymorphism and cancer risk. Thirteen case-control studies identified through PubMed and published between 2007 and 2011 with a total of 3329 cancer cases and 3979 controls were included in this meta-analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Overall, the pooled analysis showed that survivin -31C allele was associated with 1.27 fold increased risk of cancer compared with the -31G allele (95% CI = 1.091-1.479; random model). Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that survivin -31G/C polymorphism was not associated with risk of gastric cancer [OR = 2.879; 95% CI = 0.553-15.004) for CC vs.GG] and esophageal cancer [OR = 1.352; 95% CI = 0.494-3.699) for CC vs.GG]. Stratification on the basis of ethnicity showed that the risk due to -31C allele was significant only in Asian population [OR = 1.894; 95% CI = 1.206-2.974 for CC vs.GG]. The present meta-analysis suggests an important role of survivin -31 G/C polymorphism with cancer risk especially in Asian population. However, further studies with larger sample size are required to draw more comprehensive conclusions and provide more precise evidence in individual cancers.

Emerging data suggest that somatic KRAS mutation in advanced colorectal cancer is a strong predictor of non-response to anti-epidermal growth factor receptor antibody (anti-EGFR) therapy.

Published data on the association between Cyclin D1 (CCND1) G870A gene polymorphism and digestive tract cancers (DTC) are inconclusive. We carried out a meta-analysis of published case-control studies to derive a more precise estimation of the association. Relevant studies were identified from PubMed, EMBASE, and China National Knowledge Infrastructure up to February 1st, 2011. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to investigate the strength of the association. Data were available from a total of 33 case-control studies with 8534 cases and 11,737 controls. The combined results based on all studies showed that there was a statistically significant link between CCND1 G870A polymorphism and DTC risk (GG vs. AA: OR=0.83, 95%CI=0.71-0.96). In the analysis of ethnic groups, we found the A allele carriers had a significantly increased DTC susceptibility among Caucasians, but not among Asians. When stratified for tumor location, the results based on all studies only showed the variant allele 870A might have a significantly increased risk of colorectal cancer (CRC), especially of rectal cancer (GG vs. AA: OR=0.71, 95%CI=0.58-0.89). When stratifying by the stage and histological differentiation of CRC, we only observed that patients had a significantly higher frequency of CCND1 870 AA than non-cancer patients among Caucasians. The A allele carriers (hetero- or homozygotes) were significantly more common in cases with a family history of CRC than in controls. There was no evidence of publication bias for CCND1 G870A polymorphism with DTC risk. In summary, this meta-analysis demonstrates that the CCND1 G870A polymorphism may be an ethnicity-dependent risk factor for DTC. And this genetic variant may increase the risk of rectal cancer, but not colon cancer.

Increased iron overload, whether or not owing to the presence of the haemochromatosis genotype C282Y/C282Y, may be associated with an increased risk of cancer. The aim of this study was to test the hypothesis that elevated transferrin saturation levels (as a proxy for iron overload) and haemochromatosis genotype C282Y/C282Y are associated with an increased risk of cancer.

Studies investigating the association between X-ray repair cross-complementing gene 1 (XRCC1) polymorphisms and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case-control and cohort studies to better compare results between studies. Published literature from PubMed, EMBASE, and China National Knowledge Infrastructure were retrieved. 18 studies with 3,915 GC cases and 6,759 controls were selected. For XRCC1 Arg194Trp polymorphism, we only found the Trp/Trp genotype carriers might be at high risk of GC (TT vs. CC+CT: OR = 1.31, 95%CI = 1.04-1.65). When stratifying for ethnicity, the results showed there was a significant difference in genotype distribution between GC cases and controls among Asians (especially, in Chinese population), but not among Caucasians. When stratifying for control sources, significant association between Arg194Trp polymorphism and GC risk was only observed in the hospital-based controls' subgroup (TT vs. CC+CT: OR = 1.45, 95%CI = 1.13-1.87). Additionally, no significant association was detected in the gastric cardia cancer's subgroup. The results of the overall meta-analysis did not suggest any association between Arg280His/Arg399Gln polymorphisms and GC susceptibility for all genetic models. There was no evidence for the association between these two gene polymorphisms and GC risk in subgroup analyses based on study design, ethnicity, country, tumor location, Helicobacter pylori infection and the Lauren's classification of GC. In conclusion, XRCC1 Arg194Trp homozygous mutant genotype (Trp/Trp) was found to be associated with increased risk of GC.

p53 is a tumor suppressor gene and plays an important role in the etiology of breast cancer. However, studies on the association between p53 polymorphisms and breast cancer risk have yielded conflicting results. We performed a meta-analysis to investigate the association between breast cancer and the p53 polymorphisms codon 72 (27,046 cases and 30,998 controls), IVS3 16 bp (3,332 cases and 3,700 controls) and IVS6+62A>G (8,787 cases and 9,869 controls) in different inheritance models. When all the eligible studies of codon 72 polymorphism were pooled into this meta-analysis, there was no evidence of significant association between breast cancer risk and p53 codon 72 polymorphism in any genetic model. However, in the stratified analysis for Indian population, significantly association was observed in additive model (OR = 0.62, 95% CI = 0.46-0.82, P value of heterogeneity test [P (h)] = 0.153) and recessive model (OR = 0.70, 95% CI = 0.50-0.92, P (h) = 0.463). IVS3 16 bp was significantly associated with breast cancer risk in a pooled 15 studies dataset (dominant model: OR = 1.14, 95% CI = 1.02-1.27, P (h) = 0.30; recessive model: OR = 1.61, 95% CI = 1.21-2.25, P(h) = 0.25; additive model: OR = 1.66, 95% CI = 1.24-2.21, P (h) = 0.28). No significant association was found between IVS6+62A>G polymorphism and breast cancer risk in a total of 14 studies. In summary, these results indicate that IVS3 16 bp is likely an important genetic marker contributing to susceptibility of breast cancer, and codon 72 homozygous mutants may be associated with decreased breast cancer risk in Indian population.