The objective of this analysis was to examine the relationship between genomic variation and health outcomes in studies performed in non-small cell lung cancer (NSCLC) patients treated with single agent epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) using a systematic review with statistical pooling of data.

To evaluate the association between x-ray cross-complementing gene 1 (XRCC1) genetic polymorphism Arg399Gln and prostate cancer risk using a meta-analysis.

Previous studies have implicated cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (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 esophageal carcinoma and have yielded conflicting results. We undertook this study to assess possible associations of esophageal cancer risk with CYP1A1 genetic variation and GSTM1 null genotype, respectively.

Microsatellite instability (MSI) status in predicting the efficacy of adjuvant chemotherapy in colorectal cancer remains controversial.

It has been suggested that the blood clotting initiator protein, tissue factor (TF), participates in tumor growth, metastasis and angiogenesis. In addition, a family of G protein-coupled-receptors known as protease-activated receptors (PARs) has also been implicated in tumor biology. These receptors might be activated by blood coagulation proteases thus eliciting a number of pro-tumoral responses, including the expression of interleukin-8 (IL-8). Therefore, in this study we analyzed the expression of TF, PAR-1, PAR-2 and IL-8 genes in patients with esophageal cancer, one of the most aggressive neoplastic diseases. Total RNA was extracted from tissue samples (tumor and the corresponding normal mucosa) obtained from patients submitted to esophagectomy or endoscopy and further analyzed by semi-quantitative reverse transcriptase-polymerase (RT-PCR) and/or real-time quantitative PCR (qPCR). Expression of full-length transmembrane TF was significantly higher in tumor samples whereas no differences were observed in alternatively spliced TF transcripts. Tumor tissue showed increased mRNA levels for PAR-1 but not PAR-2. Remarkably, IL-8 expression was not detected in most normal tissues but showed very high expression in tumor samples. As expected, qPCR revealed greater differences in the expression pattern of all transcripts analyzed but the general profile was very similar to that observed by RT-PCR. Altogether our data suggest a possible role for blood clotting proteins in the biology of human esophageal cancer.

It was suggested that vitamin D levels influence cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. Results from previous studies on the association of VDR polymorphisms with different cancer types are somewhat contradictory, and the role of VDR in the etiology of cancer is still equivocal. We therefore performed a meta-analysis on the association between the two most studied VDR polymorphisms (FokI and BsmI) and any cancer site. Up to January 2009, we identified 67 independent studies. We used random-effects models to provide summary odds ratio (SOR) for VDR polymorphisms and cancer. We tested homogeneity of effects across studies and publication bias and explored between-study heterogeneity. When comparing FokI ff with FF carriers, we found a significant increase in skin cancer [SOR; 95% confidence intervals (CIs): 1.30; 1.04-1.61] and breast cancer (SOR; 95%CI: 1.14; 1.03-1.27) risk. For the same genotype comparison, we found a significantly higher risk of cancer when we pooled estimates from cancer sites possibly associated with vitamin D levels (prostate, breast, skin, ovary, non-Hodgkin lymphoma and colorectal). A significant reduction in prostate cancer risk was observed for carriers of BsmI Bb compared with bb genotype (SOR; 95%CI: 0.83; 0.69-0.99). In Caucasian populations, both Bb and BB carriers had a significant reduced risk of cancer at any site. In conclusion, this meta-analysis showed that VDR FokI and BsmI polymorphisms might modulate the risk of cancer of breast, skin and prostate and possibly affect cancer risk at any site in Caucasians.

NBS1 is a key DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint that plays important roles in maintaining genomic stability. The NBS1 8360G>C (Glu185Gln) is one of the most commonly studied polymorphisms of the gene for their association with risk of cancers, but the results are conflicting.

A polymorphic 9-bp deletion in exon 1 of TGFBR1 (TGFBR1*6A) has been identified as a low-penetrance cancer susceptibility allele. The strongest association in the initial studies was with breast cancer; however, these studies included patients with different types of cancer, including colon, cervical and breast carcinomas, with only a small proportion being breast cancer patients. In subsequent case-control studies focussing on breast cancer alone, the results have been equivocal. In order to clarify whether TGFBR1*6A is associated with breast cancer risk, we have genotyped this polymorphism in 988 breast cancer cases and 1,016 controls from the West of Ireland and also performed a meta-analysis of previously published data (5,150 cases and 6,344 controls). In our series from the West of Ireland, we found no association (genotypic odds ratio (OR) under a dominant model = 0.93, 95% confidence interval (CI) 0.73-1.19, P = 0.57; allelic OR = 0.93, 95% CI 0.74-1.15, P = 0.49). Meta-analysis showed evidence of heterogeneity among studies. Using the random effects model, it was found that there was no evidence of an association of the *6A allele with breast cancer (genotypic OR under a dominant model = 1.10, 95% CI = 0.94-1.28, P = 0.24, allelic OR = 1.12, 95% CI 0.97-1.31, P = 0.13). In conclusion, our study shows that there is no association between TGFBR1*6A and breast cancer risk.

To identify risk factors for induction success and overall survival (OS) and relapse-free survival (RFS) and to evaluate the impact of allogeneic stem-cell transplantation (alloSCT) in adult patients up to 60 years old with acute myeloid leukemia (AML) and reciprocal translocations involving chromosome band 11q23 [t(11q23)].

The goal of this study was to consolidate information on genetic risk factors for gastric cancer. An additional aim was to investigate the influence of race on these genetic risk associations. Relevant studies were identified from PubMed and references of retrieved articles. Meta-analysis techniques were used to summarise associations between genetic polymorphisms and gastric cancer. A total of 203 relevant studies were identified, assessing 225 polymorphisms across 95 genes. Subgroup analysis indicated that Chinese, Japanese and Korean data were consistent and could be pooled. However, 6 of 13 polymorphisms (ACE I/D, CCND1 870G>A, CDH1 -160C>A, IL1B -511C>T, IL4 -590C>T, IL10 -592A>C) displayed conflicting effects between Asian and Caucasian populations, three of which (ACE I/D, CCND1 870G>A, IL1B -511C>T) had significantly different odds ratios between the two racial groups. In total, 37 polymorphisms across 27 genes were found to be significantly associated with gastric cancer in Asians, and 12 polymorphisms across 11 genes in Caucasians. Consolidated panels of polymorphisms associated with gastric cancer risk were identified in Asians and Caucasians. The results caution against the assumption that genetic risk factors are consistent between races.

Consortia of investigators currently compile sufficiently large sample sizes to investigate the effects of low-risk susceptibility genetic variants. It is not clear how the results obtained by consortia compare with those derived from meta-analyses of published studies.

Microsatellite instability (MSI) status is a good prognostic factor for colorectal cancer (CRC), but its predictive value for chemosensitivity remains controversial. We recently performed a meta-analysis (MA) in adjuvant setting showing that MSI high (MSI-H) status did not predict the efficacy of chemotherapy. Studies were identified by electronic search through PubMed, Embase and ASCO proceedings online databases, using several keywords (colorectal cancer, chemotherapy, microsatellite instability). For each study, we calculated the ratio of response rate, complete and partial responses divided by stable disease and progression. Our MA dealt with the predictive value of MSI status on the effect of metastatic chemotherapy using various combinations of 5FU, oxaliplatin or CPT11. From 159 articles and 76 abstracts, we selected only seven independent studies. Data were analysed with a random-effect model (due to heterogeneity between studies) using EasyMA software. Statistical calculations were performed on five studies representing 860 patients (mean age 63 years; 87 MSI-H; 733 microsatellite stable [MSS] tumors). A total of 287 patients received 5FU-based chemotherapy, whereas 574 patients received combinations of 5FU or capecitabine with oxaliplatin and/or irinotecan. Our MA found no benefit of metastatic chemotherapy in terms of response rate for MSI-H patients compared with MSS patients. The global hazard ratio for response rate was 0.83 (95% confidence interval: 0.95; 0.65-1.05; p = 0.11). In conclusion, MSI status did not predict the effect of chemotherapy for metastatic CRC. Metastatic chemotherapy had a similar effect on both MSI-H or on MSS tumors.

Previous evidence implicates polymorphisms of GSTM1 and GSTT1, candidates of phase II enzymes, as risk factors for various cancers. A number of studies have conducted on the association of GSTM1 and GSTT1 polymorphism with susceptibility to nasopharyngeal carcinoma (NPC). However, inconsistent and inconclusive results have been obtained. In the present study, we aimed to assess the possible associations of NPC risk with GSTM1 and GSTM1 null genotype, respectively.

The potentially functional polymorphism, rs763110 (-844C>T), in the promoter region of the FAS ligand (FASL) gene, has been implicated in cancer risk, but individually published studies show inconclusive results. To derive a more precise estimation of the association between the FASL rs763110 and risk of cancer, we performed a meta-analysis of 19 published studies that included 11,105 cancer cases and 11,372 controls. We used odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the associations. Overall, the rs763110 CT and TT variant genotypes were associated with a significantly reduced cancer risk of all cancer types in different genetic models (homozygote comparison: OR=0.80, 95% CI: 0.68-0.95, P(heterogeneity)=0.001; heterozygote comparison: OR=0.82, 95% CI: 0.72-0.95, P(heterogeneity)<0.001; dominant model comparison: OR=0.82, 95% CI: 0.71-0.94, P(heterogeneity)<0.001; and recessive model comparison: OR=0.88, 95% CI: 0.81-0.96, P(heterogeneity)=0.074). In the stratified analyses, the risk remained for studies of the smoking-related cancers and Asian populations, or population-based studies in all the genetic models. Although some modest bias could not be eliminated, this meta-analysis suggests that the FASL rs763110 T allele has a possible protective effect on cancer risk.

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.