The -251T/A (rs4073), a single nucleotide polymorphism, has been identified in the promoter region of the interleukin-8 (IL-8) gene. It's presence could influence the production of IL-8 protein by regulating the transcriptional activity of the gene. A large number of studies have been performed to evaluate the role of -251T/A polymorphism on various cancers, with inconsistent results being reported. In this paper, we summarized 13,189 cases and 16,828 controls from 42 case-control studies and attempted to assess the susceptibility of -251T/A polymorphism to cancers by a comprehensive meta-analysis. Pooled odds ratios and 95% confidence intervals were calculated by using the random-effects model. Publication bias, subgroup, and sensitivity analysis were also performed. Results showed that the carriers of the -251A allele had about a 12-21% increased risk for the reviewed cancer, in total. The carriers of -251A had an elevated risk to breast cancer, gastric cancer and nasopharyngeal cancer and a reduced risk to prostate cancer, but no evidence was found to indicate that the -251A allele predisposed its carriers to colorectal and lung cancers. When stratified separately by 'racial descent' and 'study design', it was found that the carriers of the -251A allele among the African group, Asian group and hospital-based case-control study group were at a higher risk for cancer, but not in European group and population-based case-control study. These results show that -251A allele is susceptible in the development of low-penetrance cancers.

The association between single-nucleotide polymorphisms (SNPs) of the CYP1B1 gene and lung cancer risk is still ambiguous. In this meta analysis, we assessed 10 case-control studies included 7,067 cases and 9,374 controls of the association between CYP1B1 SNPs of Leu432Val (rs1056836, 432C>G), Asn453Ser (rs1800440, 453A>G), Ala119Ser (rs1056827, 119G>T), Arg48Gly (rs10012, 48C>G) and the risk of lung cancer. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between the polymorphism and lung cancer risk under codominant model, dominant model and additive model respectively. Although there were limitations, this meta analysis indicated that individuals with 432GG genotype had a 39.7% higher risk of having lung cancer than those with the 432CC genotype, and individuals with the 432G allele had a 26.3% increased risk as well. An increased risk of lung cancer of 2.13 fold was observed in individuals with 119TT genotype. For Arg48Gly, individuals with 48GG genotype had a significantly increased risk of lung cancer compared with individuals with 48CC (OR 3.859; 95% CI 2.536-5.87). Elevated risk of lung cancer were observed in dominant model (OR 2.115; 95% CI 1.653-2.705) as well. The risk of lung cancer was elevated as the frequency of G allele increased in additive model (P = 0.000). For individuals with the polymorphism at codon 453, no evidence of such association was observed. Furthermore, a possible association between the CYP1B1 polymorphism at codon 432 and the lung cancer could be detected in individuals of Caucasian origin, while a negative association was suggested in Asians and African-Americans. An increased lung cancer risk was also found in women with polymorphism at codon 453. These results are supportive for the hypothesis that the CYP1B1 432GG, 119TT and 48GG genotypes are low-penetrance risk factors for developing lung cancer, and further studies are needed to validate these associations.

The tumor protein p73 (TP73) gene belongs to the TP53 gene family and functions in the induction of apoptosis or cell-cycle arrest. The TP73 polymorphism (G4C14-A4T14) has been reported and many studies have focused on the role of this polymorphism in various cancers. However, the data reported for most individual cancer types were limited and not able to support a convincible conclusion. Hence, in this study, we explored the relationship between TP73 polymorphism (G4C14-A4T14) and cancer risk by carrying out a comprehensive meta-analysis. Performing both the overall and subgroup meta-analyses with a total of 23 eligible studies (6635 cases and 7378 controls in all), we detected significant cancer risk variations in the overall analysis, as well as the subgroup analysis based on ethnicity for both Asians and Caucasians. In the subgroup analysis based on source of controls, significant associations were also observed in the hospital-based controls' subgroup yet not in the population-based controls' subgroup. Furthermore, in the subgroup analysis based on cancer types, significant associations were found in colorectal cancer's subgroup but not in other cancer types' subgroups. In summary, according to the results of our meta-analysis, the TP73 polymorphism (G4C14-A4T14) probably associates with cancer risk.

Chronic myeloid leukaemia (CML) is a genetically associated malignancy of haematopoietic stem cells, characterized by a t(9;22) translocation that forms the Philadelphia chromosome and creates a novel fusion gene, BCR-ABL. Treatment with molecular-targeted therapy is usually initiated with imatinib, an inhibitor of BCR-ABL tyrosine kinase. Imatinib resistance is, however, observed in some CML patients, especially in those with advanced disease. Through computerized literature searches, a systematic analysis was conducted to examine the efficacy and benefits of dasatinib therapy for imatinib resistant or intolerant CML patients in the chronic phase (CP), accelerated phase (AP) and fatal blast crisis phase (BC). In terms of major haematological and cytogenetic responses, this meta-analysis showed no significant differences in dasatinib treatment between myeloid BC-CML and lymphoid BC-CML patients with imatinib resistance or intolerance. Dasatinib therapy was, however, significantly more effective in improving major haematological and cytogenetic responses for CP-CML patients than for AP-CML patients with imatinib resistance or intolerance.

Colorectal cancer (CRC) is a major cause of cancer mortality worldwide. There is an urgent need to search for specific and sensitive biomarkers for early diagnosis of CRC. We carried out a comprehensive systematic review of published studies that compared the miRNA expression profiles between CRC tissue and paired neighboring noncancerous colorectal tissue to determine candidate miRNA biomarkers for CRC. A miRNA ranking system that takes the number of comparisons in agreement, total study sizes and direction of differential expression into the consideration was devised and used. One of the most up-regulated miRNAs, miRNA-106a, was consistently reported to be differentially expressed in six studies and the five most down-regulated miRNAs, miR-30a-3p, miR-139, miR-145, miR-125a and miR-133a, were consistently reported to be differentially expressed in four studies. Moreover, we further validated five miRNAs in a clinical setting using qRT-PCR, which demonstrated that miR-106a expression was increased, whereas the expression of miR-30a-3p, miR-145, miR-125a and miR-133a was decreased in the CRC tissues. Therefore, these miRNAs may be the candidates to develop a panel of biomarkers with sufficient sensitivity and specificity for the diagnosis of CRC in a clinical setting.

The common genetic polymorphism for SULT1A1 is Arg213His polymorphism, which may affect the sulfation process of various environmental carcinogens and thus is suggested to be related to susceptibility of several cancers. However, studies on the association between SULT1A1 Arg213His polymorphism and cancer susceptibility are inconsistent. To assess the relationship between Arg213His polymorphism and environmental-related cancers systematically, we performed a meta analysis from 20 case-control studies including 5,915 cases and 7,900 controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of risk, we found a significant association between SULT1A1 Arg213His polymorphism and environment-related cancers (for dominant model: OR 1.22, 95% CI 1.07-1.39, P = 0.003). When stratified by ethnicity, a significant risk was observed in Asian cases, compared with controls (for dominant model: OR 1.69, 95% CI 1.17-2.43, P = 0.005). When we chose only smokers in our analysis, we also found a significantly increased risk between Arg213His polymorphism and susceptibility of environment-related cancers for participants exposed to a smoking environment. In conclusion, SULT1A1 Arg213His polymorphism, ethnicity, smoking may modulate environment-related cancer risk. Studies on gene-gene interactions in the sequential or concurrent metabolic pathway and gene-environment interactions need to be further conducted to explore the susceptibility of cancer occurrence.

Tumor necrosis factor alpha (TNF-α) is a vital cytokine involved in inflammation, immunity, and cellular organization. The TNFA-308G/A (rs1800629) and -238G/A (rs361525) polymorphisms are two widely investigated variants for their associations with risk of cervical cancer, but the results are conflicting. Here, we performed a meta-analysis to pool the data and evaluate the between-studies heterogeneity. All the case-control studies published from January 1989 to October 2010 on the association between the two polymorphisms of TNFA and cervical cancer risk were identified by searching the electronic literature Medline. The cervical cancer risk associated with the two polymorphisms of TNFA gene was estimated for each study by OR together with its 95% CI, respectively, by using the Review Manager 4.2 software. It was showed that the variant homozygote -308AA was associated with a significantly increased risk of cervical cancer (AA vs. GG: OR = 1.41, 95% CI = 1.03-1.92, P = 0.033; AA vs.

The association between the polymorphic CAG repeat in androgen receptor gene (AR) and prostate cancer susceptibility has been studied extensively. However, the results are contradictory. The purpose of our meta-analysis was to investigate whether CAG repeat related to prostate cancer risk and had genetic heterogeneity across different geographic regions and study designs. Random-effects model was performed irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. Publication bias was assessed by the fail-safe number and Egger's test. There were 16 (patients/controls: 2972/3792), 19 (3835/4908) and 12 (3372/2631) study groups for comparisons of ≥ 20, 22 and 23 repeats of CAG sequence, respectively. Compared with CAG repeat <20, 22 or 23, carriers of ≥ 20, 22 or 23 repeats had 21% (95% CI: 0.61-1.02; P = 0.076), 5% (95% CI: 0.81-1.11; P = 0.508) and 5% (95% CI: 0.76-1.20; P = 0.681) decreased risk of prostate cancer. After classifying studies by geographic areas, carriers of ≥ 20 repeats had 11% decreased risk in populations from USA, 53% from Europe, and 20% from Asia (P > 0.05), whereas comparison of ≥ 23 repeats with others generated a significant prediction in European populations (OR = 1.17; P = 0.039). Stratification by study designs revealed no material changes in risk estimation. Meta-regression analysis found no significant sources of between-study heterogeneity for age, study design and geographic region for all comparisons. There was no identified publication bias. Taken together, our results demonstrated that AR CAG repeat polymorphism with ≥ 20 repeats might confer a protective effect among the prostate cancer patients with 45 years older but not all the prostate cancer patients.

The published data on the association between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism and esophageal cancer (EC) remained controversial. The present meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A comprehensive literature search was conducted to identify all case-control studies of Lys751Gln polymorphism and risk for two main types of EC: esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma (ESCC). A total of 12 studies were identified to the meta-analysis, including 2,575 cases (1,294 ESCC and 1,281 EADC) and 4,951 controls (1,891 ESCC and 3,060 EADC). Random-effects or fix-effects model was used according to between-study heterogeneity. The odds ratio (OR) for the variant homozygous genotype Gln/Gln of the Lys751Gln polymorphism, compared with the wild type homozygote Lys/Lys, was 1.26, with 95% confidence interval (95% CI) 1.02-1.56, for EADC risk without between-study heterogeneity. When stratified by ethnicity, statistically significantly elevated risk was found among Chinese (Gln/Gln vs. Lys/Lys: OR 2.45, 95% CI = 1.10-5.44). However, no significant associations were found between XPD Lys751Gln polymorphism and EC risk when all studies pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR 1.07, 95% CI = 0.88-1.28; Gln/Gln vs.us Lys/Lys: OR 1.25, 95% CI = 0.92-1.71; dominant model: OR 1.09, 95% CI = 0.90-1.33). In conclusion, this meta-analysis suggests that the Lys751Gln genetic polymorphism may be a potential biomarker of EC susceptibility in Chinese populations. And a study with the larger sample size is needed to further evaluate gene-environment interaction on XPD Lys751Gln polymorphism and EC risk.

The results of recent published studies focusing on CYP17 polymorphisms in prostate cancer (PCa) susceptibility are often conflicting. We performed a meta-analysis based on 38 independent studies to evaluate the association.

Epidemiological studies have evaluated the association between RNASEL Asp541Glu and Arg462Gln polymorphisms and prostate cancer (PCa) risk. However, the results remain inconclusive. To derive a more precise estimation of the association between RNASEL polymorphisms and PCa risk, we performed a meta-analysis based on nineteen case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both Asp541Glu and Arg462Gln polymorphisms were not associated with PCa risk (for Asp541Glu polymorphism: Glu/Glu vs. Asp/Asp: OR 1.17, 95% CI: 0.95-1.45, P = 0.13; Glu/Asp vs. Asp/Asp: OR 1.02, 95% CI: 0.92-1.14, P = 0.70; for Arg462Gln polymorphism: Gln/Gln vs. Arg/Arg: OR 0.98, 95% CI: 0.88-1.08, P = 0.62; Gln/Arg vs. Arg/Arg: OR 0.97, 95% CI: 0.91-1.04, P = 0.53). The insignificant association was maintained in the dominant and the recessive genetic models. In subgroup analyses, the significant association was not detected in Caucasian populations. However, we found the significant association of RNASEL Asp541Glu polymorphism with sporadic PCa (Glu/Glu vs. Asp/Asp: OR 1.29, 95% CI: 1.04-1.59, P = 0.02; Glu/Asp vs. Asp/Asp: OR 1.24, 95% CI: 1.03-1.50, P = 0.03). In conclusion, we found that these RNASEL polymorphisms were not related to overall PCa risk, especially in Caucasians. However, in subgroup analyses we found a suggestion that RNASEL 541Gln allele might be a low-penetrent risk factor for sporadic PCa.

Prostate-specific antigen (PSA) screening has low specificity. Assessment of methylation status in body fluids may complement PSA screening if the test has high specificity.

Interleukin 1β (IL-1B) is a pro-inflammatory cytokine against infection, playing an important role in the pathogenesis of cancers. The -31T/C polymorphism of the interleukin 1β gene (IL1B) has been implicated in cancer risk through its influence on the IL1B transcription. However, results from studies are conflicting. To clarify the association, a meta-analysis was performed for 11 125 cases and 14 415 controls from 47 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. No significant associations were observed for total cancer from all the comparisons. Through the stratified analyses, there was a statistically significant decreased risk of hepatocellular cancer in carriers of the C allele than non-carriers (CC versus TT: OR = 0.87, 95% CI: 0.77-0.98, P(heterogeneity) = 0.103; TC versus TT: OR = 0.77, 95% CI: 0.62-0.95, P(heterogeneity) = 0.734; TC + CC versus TT: OR = 0.74, 95% CI: 0.61-0.91, P(heterogeneity) = 0.472). Similarly, decreased risk was observed for gastric cancer of the C/C genotype compared with the T/T genotype (OR = 0.87, 95% CI: 0.77-0.98, P(heterogeneity) = 0.103). Using the recessive model, a significantly decreased risk was observed for gastric cancer (OR = 0.88, 95% CI: 0.80-0.97, P(heterogeneity) = 0.158), European population (OR = 0.84, 95% CI: 0.73-0.97, P(heterogeneity) = 0.070) and positive infection-matched studies (OR = 0.75, 95% CI: 0.60-0.94, P(heterogeneity) = 0.220); however, an increased risk was found for breast cancer (OR = 1.34, 95% CI: 1.18-1.61, P(heterogeneity) = 0.116). Although some modest bias could not be eliminated, this meta-analysis suggests that the IL1B -31C allele is a low-penetrance protective factor for the development of cancer, in particular for that associated with infection.

Epidemiological studies have evaluated the association between X-ray repair cross-complementing group 1 gene (XRCC1) Arg399Gln and Arg194Trp polymorphisms and risk of prostate cancer (PCa). However, the results from the published studies on the association between these two XRCC1 polymorphisms and PCa risk are conflicting. To derive a more precise estimation of association between the XRCC1 polymorphisms and risk of PCa, we performed a meta-analysis. A comprehensive search was conducted to identify all case-control studies of XRCC1 polymorphisms and PCa risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both Arg399Gln and Arg194Trp polymorphisms were not significantly associated with PCa risk. However, in stratified analysis by ethnicity, we found that the Arg399Gln polymorphism was significantly associated with PCa risk in Asian population (Gln/Gln vs Arg/Arg: OR=1.46, 95% CI: 1.05-2.03, P=0.03; Gln/Gln vs Arg/Gln+Arg/Arg: OR=1.48, 95% CI: 1.12-1.95, P=0.01). In this meta-analysis, we found that both Arg399Gln and Arg194Trp polymorphisms were not related to overall PCa risk. However, in subgroup analysis we found a suggestion that XRCC1 399Gln allele might be a low-penetrent risk factor for PCa only in Asian men.

Studies investigating the association between X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphism Arg399Gln and hepatocellular carcinoma (HCC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship.

The G801A polymorphism in the CXCL12 gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Five published case-control studies, including 1,058 breast cancer cases and 1,023 controls were identified. No study had a deviation from the Hardy-Weinberg equilibrium (HWE) in controls. We found that the CXCL12 G801A (rs1801157) polymorphism was associated with a significantly increased risk of breast cancer risk when all studies were pooled into the meta-analysis (codomiant model: AA versus GG, OR = 1.64, 95% CI = 1.16-2.33; GA versus GG, OR = 1.42, 95% CI = 1.18-1.71; dominant model: AA/GA versus GG, OR = 1.44, 95% CI = 1.21-1.72). Furthermore, Egger's test did not show any evidence of publication bias (P > 0.05 for the dominant model). In conclusion, the results suggest that the CXCL12 G801A polymorphism may be a low-penetrant risk factor for developing breast cancer.

A number of molecular epidemiological studies have been conducted the screening for BRCA1 and BRCA2 mutations in breast cancer patients with a positive family history of breast and/or ovarian cancer and reported many common mutations in BRCA1 and BRCA2 associated in breast cancer in different population and different ethnicity. However, it's still lack of a systematic analysis on these mutations. To comprehensively evaluate the frequency and distribution of common BRCA1 and BRCA2 mutations which associated with breast cancer risk, we address this issue through system review and meta-analysis on 29 relevant published studies by conducting a literature search on PubMed and CNKI. 20 common founder germline mutations were identified from all 29 studies and 4 of BRCA1 (5382insC, 185delAG, 3819del5 and 4153delA) and 2 of BRCA2 (4075delGT, 5802del4) mutations were repeatedly reported twice or more in different articles, respectively. For the BRCA1, after conducting meta-analysis, we found that the overall frequency of 5382insC was 0.09 (95% CI 0.06-0.12), the frequency of 185delAG was 0.07 (95% CI 0.01-0.13), the frequency of 3819del5 was 0.02 (95% CI 0.01-0.04) and the frequency of 4153delA was 0.06 (95% CI 0.03-0.09). For the BRCA2, the overall frequency of 4075delGT was 0.02 (95% CI 0.00-0.03) and the frequency of 5802del4 was 0.07 (95% CI 0.04-0.11). This article provides a set of common mutations for BRCA1 and BRCA2 mutation carriers and the results may help to explore frequencies of BRCA1 and BRCA2 mutations in a given population and will be of significance both for diagnostic testing and for epidemiological studies.

The renin-angiotensin system (RAS) has been considered to be implicated in the development of breast cancer. However, the results are inconsistent. In this study, we conducted a meta-analysis to assess the association between four polymorphisms, including angiotensin I-converting enzyme (ACE) I/D and A240T, angiotensin II type 1 receptor (AGTR1) A1166C and angiotensinogen (AGT) M235T polymorphisms, and breast cancer risk. Published literature from PubMed, ISI web of science, and Embase databases were retrieved. All studies evaluating the association between ACE I/D, ACE A240T, AGTR1 A1166C, or AGT M235T polymorphism and breast cancer risk were included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Ten studies (1,650 cases and 9,283 controls) on ACE I/D polymorphism, six studies (1,316 cases and 2,632 controls) on ACE A240T polymorphism, three studies (235 cases and 601 controls) on AGTR1 A1166C polymorphism, and two studies (273 cases and 3,547 controls) on AGT M235T polymorphism were included. Overall, the meta-analysis showed no significant association between I/D or A240T polymorphism and breast cancer risk in either genetic model. Further subgroup analysis by ethnicity also revealed non-significant association in Caucasian or Asian populations except for Africans (the statistically significant association for ACE I/D or A240T polymorphism in Africans derived from only one study). A marginally significant association was observed for AGTR1 A1166C polymorphism in Caucasians (CC vs. AA: OR = 0.31, 95% CI 0.10-0.99). In addition, there was a significant association between AGT M235T polymorphism and breast cancer risk in Caucasians (OR = 1.45, 95% CI 1.12-1.88). The present meta-analysis suggested that ACE I/D and A240T polymorphisms might not be a good predictor of breast cancer risk, while AGTR1 A1166C and AGT M235T polymorphisms might be implicated in the pathogenesis of breast cancer. Given the limited sample size, the findings warrant further investigation.

MicroRNAs regulate gene expression at the post-transcriptional level and involved in diverse biological and pathological processes, including tumorigenesis. Rs11614913 in miR-196a2 and rs2910164 in miR-146a are shown to associate with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association.

Every year, 60,000 women in Germany are found to have breast cancer, and 9000 to have ovarian cancer. Familial clustering of carcinoma is seen in about 20% of cases.