Interleukin-4 (IL-4) is a typical pleiotropic T helper 2 (Th2) cytokine. This cytokine is a critical mediator of the Th1/Th2 balance and apoptosis potential and involved in the process of inflammation-mediated carcinogenesis in human organs. IL-4 gene polymorphisms influence IL-4 transcription and have been implicated in cancer risks. However, current published data show conflicts among of them. To assess the relationship between IL-4 polymorphisms and cancer risks, we performed a meta-analysis which includes 14 studies involving 3,562 cancer cases for IL-4 rs2243250 polymorphism, 6 studies involving 2,052 subjects for IL-4 rs2070874 polymorphism, and 5 studies involving 791 subjects for IL-4 intron-3 polymorphism. As for rs2243250 polymorphism, no significant association of cancer risk was found in the overall analysis. When stratified by cancer type, we observed that the IL-4 rs2243250 polymorphism was significantly associated with decreased oral cancer risk and increased renal cell cancer risk (for oral cancer, TT vs. CC: odds ratio (OR) = 0.40, 95 % confidence interval (95 % CI) 0.19-0.84, P heterogeneity = 0.662, P = 0.016; TT/CT vs. CC: OR = 0.45, 95 % CI 0.22-0.94, P heterogeneity = 0.407, P = 0.033; and for renal cell cancer, TT vs. CC: OR = 1.98, 95 % CI 1.06-3.69, P heterogeneity = 0.535, P = 0.031; TT vs.

This meta-analysis was conducted to summarize the association between an N-acetyltransferase 1 (NAT1) gene polymorphism and bladder cancer risk.

The past few years have seen flourish new biologic parameters for cancer prognosis that are revolutionizing therapeutic strategies. HER-2 is in this perspective a striking example, as it is now a key element for the care of 15-20% of breast cancer. HER-2 overexpression has first been reported as a prognostic factor before its consideration as a main parameter to predict treatment efficacy. However, although HER-2 status is now also used as a prognostic factor for many cancers, its ability to predict the action of trastuzumab in these new contexts is much lower than in breast cancer. In this literature review, we aimed to discuss HER-2 overexpression as a prognostic factor and as a predictive parameter of treatment response in selected solid tumors with a focus on adenocarcinomas.

In addition to Helicobacter pylori infection, host genetic factors contribute to gastric cancer (GC). Recognition of H. pylori is known to involve Toll-like receptors (TLR), which subsequently leads to activation of NF-κB. Thus, the overall aim of this study was to estimate for the first time the pooled effect size of polymorphisms in TLR2, TLR4 and CD14 on GC development through a meta-analysis.

The onset and progression of breast cancer (BC) is influenced by many factors, including the single nucleotide polymorphism (SNP) rs13281615 at 8q24. However, studies of the potential association between rs13281615 at 8q24 and risk of BC have given inconsistent results. We performed a meta-analysis to address this controversy.

The T241M polymorphism in the X-ray cross-complementing group 3 (XRCC3) had been implicated in cancer susceptibility. The previous published data on the association between XRCC3 T241M polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC3 T241M (61,861 cases and 84,584 controls from 157 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR]=1.07, 95% confidence interval [CI]=1.00-1.13; recessive model: OR=1.15, 95% CI=1.08-1.23; additive model: OR=1.17, 95% CI=1.08-1.28) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of bladder cancer and breast cancer, especially in Caucasians. In addition, significantly decreased lung cancer risk was also observed. In summary, this meta-analysis suggests the participation of XRCC3 T241M in the susceptibility for bladder cancer and breast cancer, especially in Caucasians, and XRCC3 T241M polymorphism is associated with decreased lung cancer risk. Moreover, our work also points out the importance of new studies for T241M association in some cancer types, such as gastric cancer, colorectal cancer, and melanoma skin cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC3 polymorphism in cancer development.

The matrix metalloproteinase (MMP) can degrade various components of the extracellular matrix and its functional genetic polymorphism may be associated with cancer development. The common MMP-7 (-181A>G) genetic polymorphism has been reported to be functional and may contribute to genetic susceptibility to cancers. However, the association between MMP-7 (-181A>G) and cancer risk remains inconclusive.

The association between the deficiency in mismatch repair (MMR) genes and prognosis in women with endometrial cancer is unclear. Here we report a systematic review and meta-analysis exploring this association.

The X-ray repair cross-complementing group 3 (XRCC3) gene has been suggested to play an important role in the pathogenesis of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of XRCC3 Thr241Met variant with HCC. The published literature from PubMed, Chinese National Knowledge Infrastructure, and Wan Fang data was retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed or random effects model. A total of five studies (1,531 HCC cancer cases and 1,952 controls) for XRCC3 Thr241Met variant were included in the meta-analysis. The meta-analysis showed that XRCC3 Thr241Met variant was associated with HCC risk under homogeneous codominant model (OR = 3.99, 95 % CI = 1.74-9.13) and recessive model (OR = 5.22, 95 % CI = 3.65-7.48), but not under heterogeneous codominant model (OR = 1.18, 95 % CI = 0.68-2.05) and dominant model (OR = 1.37, 95 % CI = 0.73-2.57). Subgroup analysis by ethnicity suggested that XRCC3 Thr241Met variant was associated with HCC risk in Chinese population, but not in Pakistani population. The present meta-analysis supported the positive association of XRCC3 Thr241Met variant with HCC in the Chinese. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

The CYP2D6 gene has been suggested to play an important role in the pathogenesis of lung cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of CYP2D6 T188C variant with lung cancer. Published literature from PubMed, Embase, Chinese National Knowledge Infrastructure and Wanfang data were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. A total of nine studies (1,516 lung cancer cases and 1,950 controls) for CYP2D6 T188C variant were included in the meta-analysis. The meta-analysis indicated that compared with CYP2D6 TT genotype, non-TT genotype (CC or CT) was significantly associated with lung cancer in the Chinese (OR = 1.61, 95 % CI = 1.38-1.87, p < 0.001), with no evidence of between-study heterogeneity (I (2) = 0.0 %, p = 0.991). The sensitivity analysis indicated that the association was stable and no publication bias was detected. The present meta-analysis supported the positive association of CYP2D6 T188C variant with lung cancer in the Chinese. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis.

The HFE gene has been suggested to play an important role in the pathogenesis of colorectal cancer. However, the results have been conflicting. In this study, we performed a meta-analysis to clarify the association of HFE gene C282Y variant with colorectal cancer. PubMed and Embase were retrieved to identify the potential literature. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. A total of eight papers including nine studies (7,588 colorectal cancer cases and 81,571 controls) for HFE gene C282Y variant were included in the meta-analysis. The result indicated that HFE gene C282Y variant was significantly associated with colorectal cancer under recessive model (OR = 2.00, 95 % CI = 1.32-3.04), with no evidence of between-study heterogeneity (I (2) = 0.2 %, p = 0.432). Further subgroup analysis by number of cases suggested the effect was significant in studies with more than 500 cases (OR = 2.51, 95 % CI = 1.58-3.98, I (2) = 0.0 %, p = 0.921), but not in studies with less than 500 cases (OR = 0.75, 95 % CI = 0.28-1.97, I (2) = 0.0 %, p = 0.622). The current meta-analysis supported the positive association of HFE gene C282Y variant with colorectal cancer. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) and risk-reducing mastectomy are widely used for BRCA1 and BRCA2 mutation carriers to reduce the risk of ovarian and breast cancer. To our knowledge, no risk-reduction therapy has addressed the BCRA1/2 carrier lifetime risk of intra-abdominal peritoneal carcinoma from an appendix source. We identified a BRCA1 carrier in a hereditary breast and ovarian cancer kindred who developed a low-grade malignant appendiceal mucocele 2 years after risk-reducing salpingo-oophorectomy. Our retrospective meta-analysis assessed the risk of intraperitoneal appendiceal cancer in BRCA1/2 carriers after RRBSO to determine whether elective risk-reduction appendectomy could reduce the incidence of intraperitoneal cancer. Data sources included the case report and 12 reports of BRCA1 and BRCA2 carriers after RRBSO with ovarian, fallopian tube, breast, and peritoneal cancer published from January 1, 1985, through April 30, 2012. Main outcome measures were nonovarian, non-fallopian tube, nonbreast, positive intra-abdominal peritoneal carcinoma in previously cancer-free BRCA1/2 carriers after RRBSO. The source of intraperitoneal cancer in BRCA1/2 carriers after risk-reducing salpingo-oophorectomy is highly likely the appendix. Use of risk-reduction appendectomy with RRBSO in younger BRCA1/2 carriers may reduce lifetime risk of malignant tumor and eliminate intraperitoneal cancer.

A summary of the evidence pertaining to the association between methylenetetrahydrofolate reductase (MTHFR) C677T and overall survival in pediatric acute lymphoblastic leukemia (ALL) is not currently available. We thus reviewed the literature on the association between MTFHR C677T and overall survival in pediatric ALL. We searched PubMed/MEDLINE, Scopus and ISI Web of Knowledge literature databases without language restrictions to identify observational studies among children diagnosed between ages 0 and 19 years that assessed MTHFR 677 polymorphisms in relation to ALL survival. We identified six studies comprising 909 pediatric patients with ALL. The magnitude of relative risk (RR) for pediatric ALL mortality varied by genotype comparison and study population, ranging from RR = 0.84 (95% confidence limits [CL]: 0.24, 3.0) for a TT vs. CT/CC comparison to RR = 7.0 (95% CL: 0.98, 49) for a TT vs. CC comparison. The current evidence suggests that individuals with MTHFR 677 variants (i.e. at least one T allele) may have a higher relative risk of pediatric ALL mortality, with greater statistical support for MTHFR 677TT. With more detailed supporting evidence, MTHFR 677 genotyping at diagnosis could provide an option for individualizing therapy and further reducing pediatric ALL mortality in certain populations.

Prostaglandin endoperoxide synthase 2 (PTGS2) is involved in prostate cancer (PCa) by stimulating cell proliferation, promoting angiogenesis, inhibiting apoptosis, and mediating immune suppression. 8473T>C, located in the 3' UTR of the PTGS2 gene, has been considered to influence PCa risk.

XRCC1-399 allele polymorphisms have been reported to be associated with susceptibility to hepatocellular carcinoma (HCC), but the conclusions of the various studies have been inconsistent. We conducted a meta-analysis of available studies to determine whether XRCC1-399 alleles influence susceptibility to hepatocellular carcinoma. We searched English-language databases, including PubMed, Medline and Embase, using terms such as "hepatocellular carcinoma" (or "HCC"), "X-ray repair cross-complementing group 1" (or "XRCC1") and "genetic polymorphism" (or "SNP"), among others; we also searched Chinese-language databases, including CNKI, VIP, Wanfang Data, and CBM, using terms such as "ganai", "ganxibaoai", "ganzhongliu", "duotaixing", and "X-xian xiufu jiaocha hubu jiyin 1". Eight independent studies, including 1604 HCC cases and 2185 controls, were included. The pooled odds ratio for XRCC1-399 was 0.99 (95% confidence interval = 0.75-1.31). We conclude that XRCC1- 399 gene polymorphisms are unrelated to risk for HCC.

Emerging evidence showed that the most common functional polymorphism (-251A>T, rs4073) in the promoter region of the interleukin-8 (IL-8) gene is involved in the regulation of the activities of interleukin-8, thus increasing an individual's susceptibility to oral cancer; but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between IL-8 -251A>T polymorphism and oral cancer risk.

The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair.

A whole-genome approach was used to investigate the genetic determinants of cytarabine-induced cytotoxicity. We performed a meta-analysis of genome-wide association studies involving 523 lymphoblastoid cell lines (LCLs) from individuals of European, African, Asian, and African American ancestry. Several of the highest-ranked single-nucleotide polymorphisms (SNPs) were within the mutated in colorectal cancers (MCC) gene. MCC expression was induced by cytarabine treatment from 1.7- to 26.6-fold in LCLs. A total of 33 SNPs ranked at the top of the meta-analysis (P < 10(-5)) were successfully tested in a clinical trial of patients randomized to receive low-dose or high-dose cytarabine plus daunorubicin and etoposide; of these, 18 showed association (P < .05) with either cytarabine 50% inhibitory concentration in leukemia cells or clinical response parameters (minimal residual disease, overall survival (OS), and treatment-related mortality). This count (n = 18) was significantly greater than expected by chance (P = .016). For rs1203633, LCLs with AA genotype were more sensitive to cytarabine-induced cytotoxicity (P = 1.31 × 10(-6)) and AA (vs GA or GG) genotype was associated with poorer OS (P = .015), likely as a result of greater treatment-related mortality (P = .0037) in patients with acute myeloid leukemia (AML). This multicenter AML02 study trial was registered at www.clinicaltrials.gov as #NCT00136084.

We conducted an updated meta-analysis to summarize the evidence from published studies regarding the association of coffee and caffeine intake with breast cancer risk.