The TP53 Arg72Pro polymorphism has been investigated as a potential genetic hallmark of esophageal cancer, but studies investigating the association between the TP53 Arg72Pro polymorphism and esophageal cancer risk have reported conflicting results. A meta-analysis was conducted to reach a conclusion on such a possible association. Computer searches of the literature were conducted in Pubmed and Embase databases and 11 published case-control studies were finally included, involving a total of 2294 esophageal cancer cases and 4034 controls. When all 11 studies were pooled into the analysis, an increased esophageal cancer risk was significantly associated with the Pro variant of TP53 Arg72Pro in three genetic comparison models [odds ratio (OR)Pro vs. Arg=1.21, 95% confidence interval (CI): 1.05-1.39, POR=0.009; ORDominant genetic model=1.22, 95% CI: 1.09-1.37, POR=0.001; ORHomozygote model=1.40, 95% CI: 1.05-1.87, POR=0.024]. In subgroup analyses based on pathological type, the Pro variant was significantly associated with an increased esophageal squamous cell carcinoma (ESCC) risk in all four genetic comparison models (ORPro vs. Arg=1.26, 95% CI: 1.08-1.47, POR=0.003; OR Recessive genetic model=1.42, 95% CI: 1.07-1.88, POR=0.015; ORDominant genetic model=1.25, 95% CI: 1.10-1.42, POR=0.001; ORHomozygote model=1.55, 95% CI: 1.14-2.10, POR=0.005), whereas the association between TP53 Arg72Pro polymorphism and esophageal adenocarcinoma risk was still uncertain owing to the limited studies included in this meta-analysis. In addition, the association between TP53 Arg72Pro polymorphism and ESCC risk was also significant in Asians. These results suggest that the Pro variant of TP53 Arg72Pro is an important genetic hallmark contributing to ESCC risk.

A number of different human leukocyte antigen (HLA) allele associations with chronic myelogenous leukemia (CML) have been previously reported. The specific associations reported in one population, however, are rarely replicated in other populations. We attempted to explore these associations by performing a meta-analysis of published studies. Following a Medline search, we identified four studies which presented raw data on all allele associations with CML (significant and non-significant). Meta-analysis of these revealed a significant risk association with the HLA-A*02 (pooled odds ratio 1.33, 95% confidence interval 1.10-1.61) allele and a significant protective effect with the HLA-B*35 allele (pooled odds ratio 0.64, 95% confidence interval 0.48-0.86). To our knowledge this is the first study to demonstrate the epidemiologic association between HLA-A*02 and the risk of CML, and we discuss this in the context of recent immunological studies reporting data on BCR-ABL fusion peptide presentation and subsequent immune response. Our findings suggest that individual epidemiological studies may lack statistical power, or may have other interfering factors which prevent the unmasking of overall associations. Meta-analyses of published studies may overcome these limitations and may prove useful in uncovering allele-disease associations.

Breast cancer as a heterogeneous disease demands reliable tools in order to identify those patients who most likely will benefit from receiving adjuvant treatment, such as chemotherapy.

The excision repair cross-complementing group 2 gene (ERCC2) plays a key role in DNA repair. Several polymorphisms in the ERCC2 gene have been described, including the commonly occurring Lys751Gln and Asp312Asn polymorphisms. Studies investigating the association of these polymorphisms with breast cancer risk produced controversial results. To evaluate these associations presented in diverse populations, we have conducted a meta-analysis based on 40 studies from 33 publications in PubMed which included analyses of Lys751Gln (14,545 cases, 15,352 controls) and Asp312Asn polymorphisms (16,254 cases, 14,006 controls). Overall findings of both polymorphisms have implicated null effects (OR = 1.01-1.03) when the analyses were limited to the statistically powerful (≥80%) studies. Although modestly increased statistically significant breast cancer risk was detected in the underpowered studies (≤80%), removal of outliers resulted in null associations. Ethnic stratification showed non-significant and relatively null associations for both polymorphisms with breast cancer risk for the overall Caucasians as well as North American and the European sub-populations. Although statistically increased and decreased risks were observed for the homogenous populations of African-Americans (Lys751Gln, OR 1.25, 95% CI 1.03-1.53, P = 0.03) and Asians (Asp312Asn, ORs: 0.53-0.55, P values: 0.02-0.03), respectively, this may be the result of small sample size. Analyses of the homogeneous adduct studies, with relatively large sample size, exhibited increased risk for Lys751Gln (OR 1.20, 95% CI (1.02-1.41), P = 0.03) and Asp312Asn (OR 1.17 95% CI 1.02-1.34, P = 0.03) under the dominant genetic model. In conclusion, our results suggest null associations of both polymorphisms in the overall and the Caucasian subgroups, although some effects can be suggested for relatively smaller minority studies. Increased risk effect was more visible when the adduct studies are considered, suggesting the role of these polymorphisms in the presence of exposure to DNA damaging agents.

Reports of BRCA genetic mutations and risk of death or recurrence are inconsistent. This study aimed to compare overall and disease-free breast cancer survival rates between BRCA1/2 mutation carriers and non-carriers for short-term and long-term outcomes separately. We searched the PUBMED and EMBASE databases and retrieved 452 articles using keywords that included breast cancer, BRCA mutation, and survival. Seventeen articles were selected for systematic review and among them 11 were included in our meta-analysis. We used the random-effects model to calculate the summary hazard ratio and corresponding 95% confidence interval. BRCA1 mutation carriers had significantly lower short-term and long-term overall survival rates (OSR) relative to non-carriers (HR = 1.92 [95% CI = 1.45-2.53]; 1.33 [1.12-1.58], respectively), while both short-term and long-term OSR of BRCA2 carriers did not differ from non-carriers (HR = 1.30 [95% CI = 0.95-1.76]; 1.12 [95% CI = 0.86-1.45], respectively). For short-term progression-free survival rate (PFSR), BRCA1 mutation carriers had a significantly lower rate than non-carriers (HR = 1.54 [95% CI = 1.12-2.12]), while BRCA2 mutation carriers had a similar PFSR (HR = 1.23 [95% CI = 0.96-1.58]). For long-term PFSRs, we found no significant results. Our results suggest that BRCA1 mutation decreases short-term and long-term OSRs and short-term PFSR, however, BRCA2 mutation does not affect either short-term or long-term survival rate, which is attributed to the different carcinogenic pathways for BRCA1 and BRCA2.

Fibroblast growth factor receptor 2 is a tyrosine kinase receptor that is a member of the family of individually distinct fibroblast growth factor receptors involved in cell proliferation, invasiveness, motility, and angiogenesis. Genome-wide association studies have identified FGFR2 as a breast cancer (BC) susceptibility gene in populations of European and Asian descent. After that, a number of studies reported that the rs2981582, rs1219648, and rs2420946 polymorphism in FGFR2 has been implicated in BC risk. However, studies on the association between these polymorphism and BC remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 46,747 cases and 87,342 controls from 16 published case-control studies was performed. Overall, significantly elevated BC risk was associated with rs2981582, rs1219648, and rs2420946 risk allele when all studies were pooled into the meta-analysis. Significant results were also observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the subgroup analysis by ethnicity, source of controls, significantly increased risks were found for these polymorphisms in all genetic model. In conclusion, this meta-analysis suggests that rs2981582, rs1219648, and rs2420946 polymorphisms in FGFR2 are associated with elevated BC risk.

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 (Lauren's 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.

A number of studies has evaluated the association between P53 codon 72 polymorphism and colorectal cancer. However, results were inconsistent. To clarify the role of this polymorphism in colorectal cancer, we conducted a meta-analysis on this topic.

Transforming growth factor-β1 (TGF-β1) is negative regulator of cell proliferation and the cell cycle, and plasma levels of TGF-β1 are twice as high in TGF-β1 -509 T homozygotes as in -509 C homozygotes. Published studies on the association between the TGF-β1 gene -509 C/T polymorphism and breast cancer risk are inconclusive, and a meta-analysis is required to verify the association. We performed a meta-analysis of four studies, including a total of 5,986 cases and 6,829 controls. Our pooled results indicate that the TGF-β1 gene -509 C/T polymorphism is not associated with breast cancer risk in a TT versus CC codominant (OR = 1.08; 95% CI = 0.87-1.34; P = 0.494), in a CT versus CC codominant (OR = 1.02; 95% CI = 0.94-1.10; P = 0.686), recessive (OR = 0.92; 95% CI = 0.83-1.03; P = 0.157), and dominant (OR = 1.03; 95% CI = 0.96-1.11; P = 0.439) models. Conclusively, this meta-analysis suggests that the TGF-β1 gene -509 T allele polymorphism does not decrease breast cancer risk.

Matrix metalloproteinase (MMP) 2, MMP7 and MMP9 are important members of the MMP family. Four polymorphisms in the promoter region of these MMPs, which are MMP2 -1306 C>T, MMP2 -735 C>T, MMP7 -181 A>G and MMP9 -1562 C>T, have been reported to be functional and may contribute to genetic susceptibility to cancers. However, the associations between these polymorphisms and cancer risk remain inconclusive due to conflicting results from different case-control studies. To better evaluate the role of these polymorphisms in cancer development, we conducted a meta-analysis that included 51 studies, with more than 40,000 subjects. The results showed that under dominant genetic model, MMP2 -1306 T was associated with lower susceptibility to lung cancer [odds ratio (OR) = 0.50, 95% confidence interval (CI) 0.43-0.59, P(heterogeneity) = 0.147, I(2) = 44.1%], head and neck cancer (OR = 0.53, 95% CI 0.41-0.69, P(heterogeneity) = 0.974, I(2) = 0.0%) and oesophageal cancer (OR = 0.67, 95% CI 0.55-0.80, P(heterogeneity) = 0.593, I(2) = 0.0%); MMP2-735T was associated with lower risk in lung cancer (OR = 0.65, 95%CI 0.53-0.79, P(heterogeneity) = 0.42, I(2) = 0.0%) and oesophageal cancer (OR = 0.84, 95% CI 0.70-0.99, P(heterogeneity) = 0.206, I(2) = 37.4%); MMP7 -181 AG and GG genotype carriers had an increased gastric cancer risk (OR = 1.90, 95% CI 1.43-2.51, P(heterogeneity) = 0.992, I(2) = 0.0%) and MMP9 -1562 C>T was not associated with cancer risk in the whole group analysis (OR = 0.99, 95% CI 0.91-1.08, P(heterogeneity) = 0.419, I(2) = 3.0%) and subgroup analyses. In all, our meta-analysis suggests that MMP2 -1306 C>T, MMP2 -735 C>T and MMP7 -181 A>G may play allele-specific roles in cancer development, while MMP9 -1562 C>T may not be a major risk factor for most cancer types. Large case-control studies should be performed to clarify the possible roles of these four polymorphisms in different kinds of cancer in more detail.

To derive a more precise estimation of the relationship between the xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism and lung cancer risk, a meta-analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the XPD Asp312Asn polymorphism and lung cancer risk. The pooled ORs were performed with co-dominant model (Asp/Asn vs. Asp/Asp, Asn/Asn vs. Asp/Asp), dominant model (Asp/Asn + Asn/Asn vs. Asp/Asp), and recessive model (Asn/Asn vs. Asp/Asp+Asp/Asn), respectively. A total of 18 studies including 7,552 cases and 9,397 controls were involved in this meta-analysis. Overall, significantly elevated lung cancer risk was associated with XPD Asn allele when all studies were pooled into the meta-analysis (Asn/Asn vs. Asp/Asp: OR=1.158, 95% CI=1.018-1.317; recessive model: OR=1.161, 95% CI=1.029-1.311). In the subgroup analysis by ethnicity, significantly increased risks were found for both Caucasians (Asn/Asn vs. Asp/Asp: OR=1.164, 95% CI=1.003-1.351; recessive model: OR=1.169, 95% CI=1.016-1.345) and Asians (Asn/Asn vs. Asp/Asp: OR=8.056, 95% CI=2.420-26.817; recessive model: OR=7.956, 95% CI=2.391-26.477). When stratified by study design, statistically significantly elevated risk was noted in hospital-based studies (Asn/Asn vs. Asp/Asp: OR=1.315, 95% CI=1.110-1.558; recessive model: OR=1.290, 95% CI=1.099-1.513). In conclusion, this meta-analysis suggests that the XPD Asn allele is a low-penetrant risk factor for developing lung cancer.

To determine whether the clinical and molecular biologic characteristics of the alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) subtypes have relevance independent of the presence or absence of the PAX/FOXO1 fusion gene.

Transforming growth factor β1 (TGF-β1) is a cytokine that plays an important role in the control of cell proliferation and differentiation in breast cancer. The -509C/T polymorphism in the TGF-β1 gene has been implicated in breast cancer risk. However, studies on the association between this polymorphism and breast cancer risk have produced conflicting results. To derive a more precise estimation of the relationship, a meta-analysis of the -509C/T polymorphism (5,825 cases and 7,953 controls) from seven published case-control studies was performed. Our analysis suggests that -509C/T has no association with breast cancer risk when using either dominant [odds ratio (OR) = 1.01, 95% confidence intervals (CI): 0.82-1.24], or recessive models (OR = 0.91, 95% CI: 0.66-1.27), or other genetic models to analyze the data. In ethnic subgroups analysis, -509C/T also did not appear to be a risk factor for breast cancer. However, larger scale primary studies are still required to further evaluate the interaction of TGF-β1 -509C/T polymorphism and breast cancer risk in specific populations.

In view of the essential role of transforming growth factorβ1 (TGFB1) on both inhibiting the development of early benign breast tumors as well as promoting tumor invasion, the association of TGFB1 L10P polymorphism and breast cancer risk has been widely reported, but results of previous studies were somewhat contradictory and underpowered. To overcome the limitations of individual study and to understand the real situation, we conducted a systematic review and meta-analysis towards the association between TGFB1 L10P polymorphism and breast cancer. Through retrieving MEDLINE, PubMed, Embase, and Web of Science, a total of 16 studies with 10,392 cases and 11,697 controls were identified. The results showed that significant association was found in the recessive genetic model for Caucasian (OR = 1.152, 95% CI = 1.020-1.301). However, we did not find any associations in additive genetic model (PP vs. LL for total: OR = 1.026, 95% CI = 0.940-1.121), allele contrast (L vs. P for total: OR = 1.004, 95% CI = 0.966-1.044), and dominant genetic model (PP + LP vs. LL for total: OR = 1.001, 95% CI = 0.946-1.061). Conclusively, this meta-analysis strongly suggests that TGFB1 L10P polymorphism may play a low penetrance role in breast cancer susceptibility in Caucasian. Large well-designed epidemiological studies will be necessary to validate the risk identified in the current meta-analysis.

Published data on the association between p21 Ser31Arg polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between the p21 Ser31Arg polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (Ser/Arg vs. Ser/Ser, Arg/Arg vs. Ser/Ser), dominant model (Arg/Arg + Ser/Arg vs. Ser/Ser), and recessive model (Arg/Arg vs. Ser/Arg + Ser/Ser). A total of 21 studies including 22,109 cases and 29,127 controls were involved in this meta-analysis. Overall, no significant associations were found between p21 Ser31Arg polymorphism and breast cancer risk when all studies pooled into the meta-analysis. In the subgroup analysis by ethnicity, significantly increased risk was found for Caucasians (Arg/Arg vs. Ser/Ser: OR 1.496, 95% CI 1.164-1.924; and recessive model: OR 1.492, 95% CI 1.161-1.919). When stratified by study design, statistically significantly elevated risk was found for population-based studies (Ser/Arg vs. Ser/Ser: OR 1.085, 95% CI 1.019-1.156). In conclusion, this meta-analysis suggests that the p21 Ser31Arg polymorphism may be associated with breast cancer development in Caucasian. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

Survivin has gradually become an important target in diagnosis, prognosis prediction and treatment of tumor. There are many studies on urine-based survivin mRNA test using reverse transcription-polymerase chain reaction (RT-PCR) as a noninvasive examination for bladder cancer. However, its clinical value remains controversial. This study was to evaluate the diagnostic value of urine survivin mRNA detection with RT-PCR for bladder cancer by a systematic review of related studies.

Life-threatening diarrhoea is observed in up to 25% of cancer patients receiving irinotecan. The associations between the UGT1A1*28 polymorphism and irinotecan-induced diarrhoea remains controversial because of conflicting data in the literature. Meta-analyses were performed on published data in terms of relationships between UGT1A1*28 and severe diarrhoea. We searched databases for relevant studies that were published in English or Chinese. Two reviewers extracted data and assessed methodological quality. UGT1A1*28 related odds ratios (ORs) were pooled by use of a fixed-effects model. The studies included were stratified into subgroups representing different races and irinotecan doses, and meta-regression analyses were performed to investigate the effect of study characteristics on the association between UGT1A1*28 and diarrhoea. Twenty trials including a total of 1760 cancer patients were included. The risk of severe diarrhoea at medium and high irinotecan doses was higher among patients with a UGT1A1*28/*28 genotype than among those with a UGT1A1*1/*1 genotype (OR=3.69, 95% confidence interval [CI]=2.00-6.83; P<0.001). Considering the patients with a UGT1A1*1/*28 genotype, the risk of toxicity was also higher than among those with a wild-type genotype at medium and high doses (OR=1.92, 95% CI=1.31-2.82; P=0.001). No association was observed between UGT1A1*28 and severe diarrhoea at low doses (<125 mg/m(2)). In conclusion, patients carrying UGT1A1*28 allele(s) are at an increased risk of irinotecan-induced severe diarrhoea. This increased risk is only apparent in those who are administrated with medium or high irinotecan doses.

In lung cancer, integrating translational data from various histologies obtained in different patients under different conditions can increase their robustness. This is a meta-analysis of cDNA array data obtained in 688 tumor patients (541 non-small cell lung cancer, 33 small cell lung cancer and 114 others) and 205 controls. 1,206 genes were found to be dysregulated in one of the 12 transcriptomics studies available. 748 results (62%) were obtained only once and might be questioned. 38% of observations could be reproduced twice or more. 346 genes were reported twice, 80 three times, 27 four and 5 five times. A common set of genes dysregulated in lung cancer was obtained, including BPA1, DUSP6, ASCL1, RNAS1 and S100P. p63 and CK 5/6 p63 are useful for differentiating adenocarcinoma and small cell lung cancer from squamous cell carcinoma. TFF-3 and MUC1 are over-expressed in adenocarcinoma. INSM1, SGNE1 and H2AFZ are typical for small cell lung cancer. Using a meta-analysis approach, it was possible to detect a robust set of genes differentially expressed in lung cancer and to determine a limited number of key genes linked to subtypes in lung cancer molecular pathology.

The association between transforming growth factor-beta1 (TGF-beta1) gene polymorphisms and breast cancer risk has been widely reported, but results were somewhat controversial and underpowered. To derive a more precise estimation of the relationship between TGF-beta1 polymorphisms and breast cancer risk, we conducted a meta-analysis of all available case-control studies relating the T869C and/or C-509T polymorphisms of the TGF-beta1 gene to the risk of developing breast cancer. Eligible articles were identified by search of databases including MEDLINE, PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database (CBM) for the period up to March 2010. Finally, a total of 17 articles involving 27 case-control studies were identified, 25 with 20,022 cases and 24,423 controls for T869C polymorphism and eight with 10,633 cases and 13,648 controls for C-509T polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. Subgroup analysis was also performed by ethnicity for T869C polymorphism. With respect to T869C polymorphism, no association was found in overall analysis (C vs. T: OR = 1.033, 95% CI = 0.996-1.072). In the subgroup analysis by ethnicity, significantly increased risk was found in Caucasian population (C vs. T: OR = 1.051, 95% CI = 1.018-1.085; CC vs. TT + TC: OR = 1.083, 95% CI = 1.019-1.151), but not in Asian population (C vs. T: OR = 1.054, 95% CI = 0.983-1.130). With respect to C-509T polymorphism, no significant association with breast cancer risk was demonstrated in overall analysis (T vs. C: OR = 0.986, 95% CI = 0.936-1.039). It can be concluded that potentially functional TGF-Beta1 T869C polymorphism may play a low penetrance role in breast cancer susceptibility in an ethnicity-specific manner.

Cetuximab has a favorable effect on patients with metastatic colorectal cancer harboring wild K-ras gene. This meta-analysis was planned to quantify the benefit.