Sex hormone-binding globulin (SHBG) is a plasma glycoprotein that plays an important role in breast cancer pathophysiology and risk definition, since it regulates the bioavailable fraction of circulating estradiol. Epidemiological studies have evaluated the association between SHBG Asp327Asn polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 10 studies were identified for the meta-analysis, including 10,454 cases and 13,111 controls for SHBG Asp327Asn polymorphism. When all studies were pooled into the meta-analysis, there was no evidence for significant association between SHBG Asp327Asn polymorphism and breast cancer risk (for Asn/Asn vs. Asp/Asp: OR = 1.20, 95 % CI = 0.94-1.55; for Asp/Asn vs. Asp/Asp: OR = 0.94, 95 % CI = 0.87-1.01; for dominant model: OR = 0.95, 95 % CI = 0.90-1.02; for recessive model: OR = 1.22, 95 % CI = 0.95-1.57). In the subgroup analyses by ethnicity, menopausal status, and source of controls, no significant associations were found in all genetic models. Interestingly, further analyses stratified by menopausal status in different ethnicities revealed that this polymorphism might provide protective effects against breast cancer risk in postmenopausal Asian women (for dominant model: OR = 0.83, 95 % CI = 0.70-0.97). Sensitivity analyses were performed by sequential removal of individual studies and cumulative statistics have showed combined ORs were not materially altered by any individual study under all comparisons. In summary, this meta-analysis suggests that SHBG Asp327Asn polymorphism is not associated with breast cancer risk overall, while it might be an important genetic susceptibility factor in postmenopausal Asian women for developing breast cancer. Larger and well-designed studies are warranted to confirm our findings in the future.

Recently, genome-wide association studies (GWAS) have identified over 12 single-nucleotide polymorphisms (SNPs) associated with bladder cancer risk in populations of European descent. However, effects of these SNPs in bladder cancer have not been systemically evaluated in the Chinese population. We conducted association studies of 12 SNPs in a Chinese population of 184 cases and 962 controls. These SNPs were previously identified in European GWAS and a fine mapping study. The reported risk alleles of rs798766 on TACC3 at 4p16 and rs9624880 on MYC at 8q24 were significantly associated with increased bladder cancer risk with P-values of 0.003 and 0.03, respectively. Next, we performed a meta-analysis, by combining our study with previous association studies performed in Chinese. In the meta-analysis, the reported risk allele for four SNPs were significantly associated with increased bladder cancer risk, including rs798766 on TACC3 at 4p16, rs9624880 on MYC at 8q24, rs2294008 on PSCA at 8q24, and rs2736100 on TERT at 5p15. The meta-analysis P-values for the four SNPs ranged from 0.017 to 5.52E-05. The results from our study suggest that a sub-set of bladder cancer risk-associated SNPs identified from the European population are also associated with bladder cancer risk in the Chinese population. Additional studies with larger sample sizes are needed to further confirm our results.

The association of two cytochrome P4501A1 (CYP1A1) polymorphisms, m1 (T6235C transition) and m2 (A4889G transition), with gastric cancer risk is inconclusive. We conducted a meta-analysis of all available studies to evaluate the potential role of the polymorphisms and their interactions with tobacco smoking in gastric cancer susceptibility. Published literature from PubMed was retrieved by two investigators independently. Fourteen case-control studies with 2,032 gastric cancer cases and 5,099 controls were selected. A fixed effects model or a random-effects model was used to estimate the odds ratio (OR) for the CYP1A1 polymorphisms and the occurrence of gastric cancer. Significant associations between CYP1A1 m1 and m2 polymorphisms and gastric cancer susceptibility were not observed in all genetic models in the overall analyses. Subgroup analyses by ethnicity and source of controls did not reveal significant associations with gastric cancer risk. Stratification analysis by smoking status found that carriers of the heterozygous and homozygous m1 genotypes decreased the susceptibility of gastric cancer among ever-smokers (pooled OR = 0.56, 95 % CI 0.36-0.89, fixed effects). In contrast, the m2 genotypes (G/G and A/G) did not show any relevance to gastric cancer risk among the smoking population (pooled OR = 1.30, 95 % CI 0.84-2.00, fixed effects). Overall, we found that the CYP1A1 polymorphism itself, either m1 or m2, did not represent an independent genetic risk factor influencing gastric cancer. However, subgroup analyses suggest that carriers of the heterozygous and homozygous m1 genotype who are exposed to tobacco smoke have a significantly lower risk of developing gastric cancer. To explain the observed reduction of gastric cancer risk, we proposed a novel hypothesis of "observation bias". This hypothesis is also applicable to explain the combined effects of other genetic polymorphisms and environmental factors on the risk of developing cancers, and the rationality of the hypothesis needs to be further investigated.

To investigate the association between p53 codon 72 polymorphisms and gastric cancer risk, a meta-analysis published in 2007 was updated with new data. Relevant literature was retrieved by searching PubMed and statistical analysis conducted using Review Manager software. Twenty-eight case-control studies were included in this meta-analysis, with 6,859 cases and 9,277 controls. The pooled results for all included studies showed that patients with gastric cancer had a borderline lower frequency of the Arg/Arg phenotype (odds ratio (OR) = 0.91, 95 % CI = 0.83-1.00, p = 0.04). When stratified for race, the difference in Arg/Arg frequency was significant among Asians (OR = 0.87, 95 % CI = 0.78-0.97, p = 0.01). On stratifying the various studies we found that, among Asians: (i) patients with cardial gastric cancer had a significantly higher frequency of the Pro/Pro genotype (OR = 1.35, 95 % CI = 1.03-1.77, p = 0.04) than those with non-cardial gastric cancer; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/Arg (OR = 1.30, 95 % CI = 1.06-1.61, p = 0.01) than those with early (stage I/II) cancer; and (iii) patients with metastasis had a significantly higher frequency of Pro/Pro (OR = 3.31, 95 % CI = 1.31-8.41) than those without metastasis. Our study suggests that, among Asians, the p53 codon 72 Arg/Arg genotype is associated with a modestly decreased risk of gastric cancer, and that this difference in genotype distribution may be associated with cancer stage, location, differentiation and metastasis.

Published data have shown conflicting results about the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms (Arg399Gln and Arg194Trp) and clinical outcome of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis is needed to provide a systematic review of the published findings.

The association between polymorphisms on 15q25.1 and lung cancer has been widely evaluated; however, the studies have yielded contradictory results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on two polymorphisms (CHRNA3 gene: rs1051730 and AGPHD1 gene: rs8034191) on 15q25.1.

To examine the association between glutathione peroxidase 1 (GPx1) gene Pro198Leu polymorphism with the development and progression of prostate cancer. A comprehensive search was conducted to identify all case-control studies of GPx1 polymorphisms and prostate cancer. Statistical analysis was performed with the software program Stata, version 11.0, and Review Manage, version 4.2. A total of 7 eligible studies relating the GPx1 polymorphism to the risk of prostate cancer were identified. The results indicated no significant association between GPx1 polymorphisms and prostate cancer susceptibility in the dominant model (random effects OR 0.75, 95 % CI 0.48-1.18), recessive model (random effects OR 0.47, 95 % CI 0.22-1.01) and co-dominant genetic model (random effects OR 0.72, 95 % CI 0.43-1.21). For the analysis of GPx1 polymorphism and progression of prostate cancer, no significant association were found in the dominant model (fixed effects OR 1.20, 95 % CI 0.95-1.52), recessive model (fixed effects OR 0.69, 95 % CI 0.48-1.00) and co-dominant genetic model (fixed effects OR 0.95, 95 % CI 0.79-1.15). Egger's test showed that publication bias was not present in all the comparisons.

Cetuximab, a monoclonal antibody against the epidermal growth factor receptor, inconsistently improves response rates (RR), progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced colorectal cancer patients with K-ras wild-type (WT) tumors.

Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements, the molecular mechanisms driving medulloblastoma are not fully understood and further elucidation could provide cues to improve outcome prediction and therapeutic approaches.

A number of studies focusing on the association between the exon 1 CAG repeat polymorphism of the androgen receptor (AR) gene and polycystic ovary syndrome (PCOS) have revealed conflicting results. The current systematic review and meta-analysis was conducted to quantify the strength of the association and to explore potential sources of heterogeneity that may have influenced the results. Studies matched to search terms from PubMed, EMBASE and HuGE Navigator published through to 31 January 2012 were retrieved. Data extraction from the included studies was carried out by two authors independently. Weighted mean differences (WMDs) of biallelic mean and odds ratios (ORs) of alleles and genotypes were pooled for meta-analysis. Sixteen articles reporting on 17 studies were included. In continuous data analysis, the summary WMD was -0.06 (95% confidence interval -0.29 to 0.16). In dichotomous data analysis, we divided the alleles into short and long alleles and calculated the summary ORs. No statistically significant results were identified by different comparison models or different cut-off point definitions. No publication bias was observed in continuous and dichotomous data analysis. In summary, the current systematic review and meta-analysis found that the AR CAG microsatellite repeat polymorphism is unlikely to be a major determining factor in the development of PCOS.

Greater height has been associated with increased risk of several cancers, but epidemiological data on height and pancreatic cancer are inconclusive. We conducted a systematic review and meta-analysis of prospective studies to clarify these results.

The association between transforming growth factor β1 (TGF-β1)-509 C>T and risk of digestive tract cancer (DTC) remained uncertain as previous studies reported conflicting results. The aim of this study was to assess the association by using a meta-analysis. The databases of MEDLINE, EMBASE and WANGFANG (Chinese database) were retrieved, and latest update was on 2nd February, 2012. Pooled odds ratio and 95% confidence interval (OR and 95% CI) were calculated by using a fixed- or random-effect model. Ultimately, twenty nine case-control studies with 8664 cases and 12,532 controls were included in this meta-analysis. Overall, there was no association between TGF-β1-509 C>T and risk of DTC in all genetic comparison models (OR and 95% CI: 0.96 and 0.81-1.15 for TT vs. CC, 0.98 and 0.91-1.05 for T carriers vs. C carriers). When subgroup analyses were conducted according to ethnicity, types of cancer and sample size, T allele was significantly associated with decreased risk of DTC for Caucasians and for large sample-sized studies, and was associated with decreased risk of colorectal cancer (OR and 95% CI for TT vs. CC: 0.82 and 0.70-0.97 for Caucasians, 0.80 and 0.68-0.98 for large sample-sized studies, 0.78 and 0.62-0.97 for colorectal cancer). This study indicated that TGF-β1-509 C>T polymorphism was probably associated with risk of DTC, especially for Caucasians. Because of modest limitation, our findings should be confirmed by future studies.

Pre-emptive irinotecan dose reduction for UGT1A1*28 homozygotes may result in reduced risk of severe neutropenia and diarrhea. However, clinical utility and cost-effectiveness are dependent upon such a dose reduction not impacting irinotecan efficacy. Whether UGT1A1*28 genotype is associated with irinotecan response therefore is an important gap in existing knowledge to inform clinical utility.

Studies focused on the correlation of mutations in the genome of Hepatitis B Virus (HBV) like Pre-S mutation, Basal Core promoter (BCP), Enhancer II (EnhII), especially Precore mutation, with the risk of hepatocellular carcinoma (HCC) have triggered stiff controversies. With an increasing number of studies in this field recently, we conducted this meta-analysis to appraise the correlations.

Alcohol dehydrogenase 1C (ADH1C) is the key enzyme catalyze oxidation of alcohol to acetaldehyde, which plays vital roles in the etiology of various cancer. To date, studies investigated the association between a functional polymorphism in ADH1C, Ile350Val (rs698), and risk of cancer have shown inclusive results.

Lung cancer is the major cause of cancer death globally, it is often diagnosed at an advanced stage and has one of the lowest survival rates of any type of cancer. The common interest in the field of lung cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. There is increasing evidence to suggest that microRNAs play important and complex roles in lung cancer.

Published data regarding the association between alcohol dehydrogenase (ADH) 1C genotypes and breast cancer risk show conflicting results. The authors performed this meta-analysis on 1969 patients and 2244 controls from 4 (including 7 study populations) related case-control studies to estimate the association between ADH1C(rs698) genotyping information and breast cancer risk. According to the 6 eligible populations, the odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk for ADH1C (1-2) versus ADH1C (2-2) , ADH1C (1-1) versus ADH1C (2-2) genotype, and ADH1C (1) versus ADH1C (2) were 1.16 (0.95-1.42), 1.17 (0.95-1.44), and 1.05 (0.96-1.16), respectively. The OR (95% CI) for ADH1C (1-1) + ADH1C (1-2) versus ADH1C (2-2) from the 7 study populations was 1.14 (0.96-1.36). Meanwhile, genotypes of ADH1C (1-1) + ADH1C (1-2) increased the risk of breast cancer in drinkers (OR = 1.35; 95% CI = 1.03-1.76). This meta-analysis suggested that the ADH1C (1) allele might modestly influence the effect of alcohol on breast cancer but is not an independent risk factor for breast cancer. However, more restricted prospective studies are needed.

The association between Asp312Asn and Lys751Gln polymorphisms of Xeroderma pigmentosum Group D (XPD) and prostate cancer risk are still inconclusive. For better understanding of the effects of these two polymorphisms on prostate cancer risk, a meta-analysis was performed.

Interleukin-10 (IL-10) plays a key role in immunosuppressive and anti-angiogenic process, suggesting its possible involvement in carcinogenesis. A haplotype formed by polymorphisms at positions -1082 G/A (rs1800896), -819 T/C (rs1800871), and -592 A/C (rs1800872) from the transcriptional start site in the promoter region of the IL-10 gene is a strong determinant for IL-10 production. We systematically reviewed the evidence of association between IL-10 promoter haplotype and cancer risk. Up to November 2011, databases including PubMed, and CNKI (China National Knowledge Infrastructure) were searched to access the relevant genetic association studies. Summary odds ratios and corresponding 95% confidence intervals (CIs) for this haplotype and cancer risk were estimated by using fixed or random-effect models when appropriate. Finally, 12 case-control studies with 2,090 cases and 4,224 controls were available for this study. The summary OR for cancer risk associated with the GCC haplotype was 1.47 (95 % CIs = 1.25-1.72) when compared with ATA haplotype by random effects model. Similarly, significantly increased risks were observed both in Caucasian and in Non Caucasian. Our results suggested that haplotype in IL-10 promoter was involved in the development of cancer.

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.