Several studies have investigated the associations between RAD51 G135C polymorphism and the susceptibility to breast cancer, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 case control studies, including 12,153 cases and 10,245 controls, were selected. Overall, significant decreased risk was found for the additive model (OR = 0.995, 95% CI = 0.991-0.998) and dominant model (OR = 0.994, 95% CI = 0.991-0.998). In the subgroup analysis by ethnicity, statistically significantly decreased risk was found in Asians (additive model: OR = 0.977, 95% CI = 0.954-1.000 and dominant model: OR = 0.981, 95% CI = 0.963-1.000). In conclusion, this meta-analysis suggests that the RAD51 G135C polymorphism is a low-penetrant risk factor for developing breast cancer.

To assess the association between tumor necrosis factor-alpha (TNF-alpha) gene promoter region -308 gene polymorphisms and gastric cancer (GC) susceptibility.

CCND1 plays a critical role in cell cycle control and may contribute to head and neck cancer. We performed a meta-analysis of eleven case-control studies that examined the association between CCND1 G870A polymorphism and head and neck cancer risk. Overall, no significant association of this polymorphism with head and neck cancer was found (for AA vs. GG: OR=0.96, 95% CI=0.59-1.58, P<0.01 for heterogeneity; for GA vs. GG: OR=1.00, 95% CI=0.74-1.35, P<0.01 for heterogeneity; for the dominant model GA/AA vs. GG: OR=0.98, 95% CI=0.69-1.39, P<0.01 for heterogeneity; for the recessive model AA vs. GG/GA: OR=0.94, 95% CI=0.66-1.33, P<0.01 for heterogeneity). In subgroup analysis by ethnicity, we also did not find any significant association in European and Asians populations. All the results were not materially altered in any genetic model after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded. In conclusion, our meta-analysis strongly suggested that the CCND1 G870A polymorphism is not associated with head and neck cancer risk.

To investigate the association between peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene polymorphism 34 C>G and colorectal cancer (CRC), a meta-analysis review was performed in this report.

Interleukin-1β (IL-1β), which is involved in inflammatory and immunological responses, plays an important role in the development and progression of breast cancer. Three functional single nucleotide polymorphisms (SNPs) identified in IL-1β gene are thought to influence breast cancer risk. The results of the association between IL-1β polymorphisms and breast cancer remain inconsistent. Therefore, we conducted a meta-analysis of eight case-control studies with rs1143627 (T > C), rs16944 (C > T), and rs1143634 (C > T). We found that the variant CC genotype of rs1143627 was associated with a significantly increased breast cancer risk (CC vs. TT: OR = 1.37, 95% CI = 1.10-1.70, P = 0.22 for heterogeneity; the recessive model CC vs. TT/TC: OR = 1.40, 95% CI = 1.17-1.67, P = 0.49 for heterogeneity). For rs16944 (C > T) and rs1143634 (C > T), no significant associations were found in all genetic models. In conclusion, the present meta-analysis suggests that rs1143627 is associated with breast cancer risk.

Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines.

Androgens have been hypothesized to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol and their binding to the estrogen receptor and/or androgen receptor (AR) in the breast. The CAG repeat polymorphism in AR exon 1 has been implicated in breast cancer risk; however, studies on the association between this polymorphism and breast cancer risk remain conflicting. In order to derive a more precise estimation of the relationship, a large population-based case-control study was performed. We found that a long CAG sequence has a protective effect on breast cancer using an a priori determined cutoff (< 22 or ≥ 22) in a dominant model analysis [SL-LL vs. SS, odds ratio (OR) = 0.86, 95% confidence intervals (CI): 0.67-1.10]. A similar result was obtained by analyzing seven detailed genotyping case-control studies by allele comparison in dominant and recessive models. However, larger scale primary study is required to further evaluate the interaction of AR CAG polymorphism and breast cancer risk.

Polymorphisms in DNA repair genes have been reported contributing factors in head and neck cancer risk but studies have shown conflicting results.

Nitric oxide (NO) is known to be critically involved in breast carcinogenesis. Genetic polymorphisms of the gene encoding for endothelial nitric oxide synthase (eNOS), the enzyme catalyzing the production of the NO, are known to predispose to malignant disease. Increasing evidences showed that eNOS plays a significant role in the development of breast cancer. However, published data on the association between eNOS 894 G>T polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of this relationship, a meta-analysis including 11 studies was performed. Crude odds ratios (ORs) with 95% confidence interval (CIs) were used to estimate the strength of the association. The results showed that there was a significant association with breast cancer risk in TT versus GG (OR = 1.22, 95% CI = 1.02-1.44, P = 0.272) and recessive model TT versus GG/GT (OR = 1.21, 95% CI = 1.02-1.42, P = 0.223). In summary, this meta-analysis primarily suggests that eNOS 894G>T polymorphism is associated with breast cancer.

Myeloperoxidase (MPO) is an endogenous oxidant enzyme that generates reactive oxygen species and plays an important role in the aetiology of cancer. The MPO -463G>A polymorphism influences MPO transcription and has been implicated in cancer risk. However, results from published studies on the association between the MPO -463G>A polymorphism and risk of cancer are conflicting. To derive a more precise estimation of association between the MPO -463G>A polymorphism and risk of cancer, we performed a meta-analysis based on 43 case-control studies, including a total of 14 171 cancer cases and 17 319 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the -463A allele had a 0.93-fold lower cancer risk in a dominant model (OR = 0.93, 95% CI = 0.87-1.00). In the stratified analyses, we observed a similar association in European populations (heterozygote comparison: OR = 0.90, 95% CI = 0.82-0.99) and hospital-based studies (dominant model: OR = 0.88, 95% CI = 0.79-0.99). When stratified by cancer type, however, no significant association was found. The results suggested that the MPO -463A allele does not contribute to the development of cancer. Additional well-designed large studies are required to validate these findings in different populations.

Methionine synthase reductase (MTRR) is one of the important enzymes involved in the folate metabolic pathway and its functional genetic polymorphisms may be associated with breast cancer risk. However, this relationship remains inconclusive. For better understanding the effect of MTRR A66G polymorphism on breast cancer risk, a meta-analysis was performed. By searching PubMed and EMBASE, a total of six case-control studies, containing 6,084 cases and 6,756 controls, were included. The strength of association between MTRR A66G polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The results strongly suggested that there was no significant association between MTRR A66G polymorphism and breast cancer susceptibility in overall comparisons in all genetic models (additive model: OR 1.00, 95% CI 0.89-1.11, P = 0.943; dominant model: OR 1.00, 95% CI 0.91-1.10, P = 0.989; recessive model: OR 1.00, 95% CI 0.91-1.09, P = 0.926). Similarly, in subgroup analyses for ethnicity (Caucasian, Asian and mixed population) and folate intake status (high and low folate intake), the results were negative. Sensitivity analysis demonstrated that omitting any study did not perturb the results. In conclusion, this meta-analysis strongly suggests that MTRR A66G polymorphism is not associated with breast cancer risk, especially in Caucasians and Asians.

To clarify the association between XRCC1 haplotypes and susceptibility to breast cancer, a meta-analysis of case-control studies were conducted. Eligible studies were identified by searching several databases for relevant reports published before March 2010. In total, 10 studies were included in the present meta-analysis. XRCC1 haplotypes for Arg194Trp and Arg399Gln polymorphisms were included in the analysis. The association was measured using random-effect model or fixed-effect model odds ratio (OR) combined with 95% confidence intervals (CIs) according to the between studies' heterogeneity. Large between-study heterogeneity was observed (Q = 25.587, df = 9, P < 0.001). The meta-analysis showed a borderline increased risk of breast cancer associated with the Arg194-Gln399 haplotype versus the Arg194-Arg399 haplotype (OR = 1.07, 95% CI: 1.01-1.14). There was no significant association between XRCC1 haplotypes and risk of breast cancer among Caucasoid subjects. In the next step, studies were classified according to geographical locations. Studies reported form Western populations did not show heterogeneity, and the Arg194-Gln399 haplotype was not associated with risk of breast cancer in comparison with the Arg194-Arg399 haplotype (OR = 1.02, 95% CI: 0.95-1.09). Among studies reported form Asian countries, significant heterogeneity was observed. After excluding of one study which did not show linkage disequilibrium, heterogeneity between studies decreased and haplotype Arg194-Gln399 revealed significant association with increased risk of breast cancer compared with haplotype Arg194-Arg399 (OR = 1.26, 95% CI: 1.04-1.50). There was no significant association between Trp194-Arg399 haplotype and risk of breast cancer, neither in Western nor Asian countries. The present meta-analysis has indicated that the Arg194-Gln399 haplotype of XRCC1 might be a risk factor for breast cancer in Asian countries.

To date, case-control studies on the association between methylenetetrahydrofolate reductase (MTHFR) C677T and childhood acute lymphoblastic leukemia have provided either controversial or inconclusive results. To clarify the effect of MTHFR C677T on the risk of childhood acute lymphoblastic leukemia, a meta-analysis of all case-control observational studies was performed. Heterogeneity (I(2)=65%, P<0.0001) for C677T among the studies was extreme. The random effects (RE) model showed that the 677T allele was not associated with a decreased susceptibility risk of childhood acute lymphoblastic leukemia compared with the C allele [OR=0.96, 95% confidence interval (CI) (0.88-1.04), P=0.34]. The contrast of homozygotes, recessive model and dominant model produced the same pattern of results as the allele contrast. Although MTHFR C677T was associated with increased risks of colorectal cancer, leukemia, and gastric cancer, our pooled data suggest no evidence for a major role of MTHFR C677T in the carcinogenesis of childhood acute lymphoblastic leukemia.

Preclinical cellular response profiling of tumor models has become a cornerstone in the development of novel cancer therapeutics. As efforts to predict clinical efficacy using cohorts of in vitro tumor models have been successful, expansive panels of tumor-derived cell lines can recapitulate an "all comers" efficacy trial, thereby identifying which tumors are most likely to benefit from treatment. The response profile of a therapy is most often studied in isolation; however, drug treatment effect patterns in tumor models across a diverse panel of compounds can help determine the value of unique molecular target classes in specific tumor cohorts. To this end, a panel of 19 compounds was evaluated against a diverse group of cancer cell lines (n = 311). The primary oncogenic targets were a key determinant of concentration-dependent proliferation response, as a total of five of six, four of four, and five of five phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, insulin-like growth factor-I receptor (IGF-IR), and mitotic inhibitors, respectively, clustered with others of that common target class. In addition, molecular target class was correlated with increased responsiveness in certain histologies. A cohort of PI3K/AKT/mTOR inhibitors was more efficacious in breast cancers compared with other tumor types, whereas IGF-IR inhibitors more selectively inhibited growth in colon cancer lines. Finally, specific phenotypes play an important role in cellular response profiles. For example, luminal breast cancer cells (nine of nine; 100%) segregated from basal cells (six of seven; 86%). The convergence of a common cellular response profile for different molecules targeting the same oncogenic pathway substantiates a rational clinical path for patient populations most likely to benefit from treatment. Cancer Res; 70(9); 3677-86. (c)2010 AACR.

Proto-oncogene HER2 (also known as erbB-2 or neu) plays an important role in the carcinogenesis and the prognosis of breast cancer. Many epidemiological studies have been conducted to explore the association between the HER2 Ile655Val polymorphism and breast cancer risk. However, inconsistency existed in the results. Therefore, we performed a meta-analysis of 27 published case-control studies including 11,504 cases and 12,538 controls. We assessed the strength of the association by crude odds ratios (ORs) with 95% confidence intervals (CIs) and reached a result that HER2 Ile655Val polymorphism was associated with an increased breast cancer risk in overall populations (for Ile/Val vs. Ile/Ile: OR = 1.05, 95% CI = 1.00-1.12, P = 0.07 for heterogeneity; for the dominant model Ile/Val + Val/Val vs. Ile/Ile: OR = 1.10, 95% CI = 1.01-1.20, P = 0.01 for heterogeneity). In subgroup analysis by ethnicity, we found a significant association among Africans (for Val/Val vs. Ile/Ile: OR = .78, 95% CI = 1.94-39.72, P = 0.35 for heterogeneity; for the recessive model Val/Val vs. Ile/Val +Ile/Ile: OR = 8.60, 95% CI = 1.92-38.48, P = 0.31 for heterogeneity) and Asians (for Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01-1.39, P = 0.41 for heterogeneity; for the dominant model Val/Val + Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01-1.38, P = 0.27 for heterogeneity). In conclusion, our meta-analysis suggests that HER2 Ile 655Val polymorphism may contribute to breast cancer risk.

Growing evidence suggests that interleukin-8 (IL-8) play pivotal roles in the pathogenesis of cancer through the modulation of tumour immune response or enhanced angiogenesis. A single nucleotide polymorphism, -251A/T, has been identified in the promoter region of the IL-8 gene and has been shown to influence its production. Results from previous studies on the association of -251A/T polymorphism with different cancer types remained contradictory. To assess the effect of -251A/T of IL-8 on cancer susceptibility, we conducted a meta-analysis, up to May 2009, of 14,876 cases with different cancer types and 18,465 controls from 45 published case-control studies. Summary odds ratios and corresponding 95% confidence intervals (CIs) for IL-8 polymorphism and cancer were estimated using fixed- and random-effects models when appropriate. The AA/AT genotypes were associated with a significantly increased risk of nasopharyngeal carcinoma when compared with TT genotype (OR=1.48; 95% CI, 1.16-1.89). Moreover, significantly elevated risks were observed in 'other cancers', and also in African population when population is concerned. Interestingly, when stratified separately by population-based studies and hospital-based studies, significantly elevated risk was found among hospital-based studies (OR=1.21, 95% CI, 1.07-1.37), whereas significantly decreased risk was found among population-based studies (OR=0.90, 95% CI, 0.83-0.97). This meta-analysis shows that IL-8 -251A/T polymorphism may play a complex role in cancer development.

In this study, two polymorphisms of follicle stimulating hormone receptor (FSHR) gene were analysed in the case-control sample using 40 premature ovarian failure (POF) patients, 60 polycystic ovary syndrome (PCOS) patients and 92 healthy controls. All subjects were unrelated Han Chinese from Shanghai. No difference was observed on the allelic or genotypic distribution of FSHR gene polymorphisms between the groups. However, the two-marker haplotypes covering components Thr307Ala (rs6165) G and Asn680Ser (rs6166) A were observed to be significantly associated with PCOS (p=0.007, corrected p=0.042). Meanwhile, a meta-analysis including our study (altogether six POF and eight PCOS studies) showed significant association between rs6166 marker and PCOS (p<0.05). The results suggest that FSH receptor might play a role in genetic susceptibility to PCOS. However, confirmatory studies in independent samples are needed.

RAD51 plays a key role in homologous recombination repair of double-stranded DNA breaks which may cause chromosomal breaks and genomic instability. We performed a meta-analysis of 9 epidemiological studies involving 13,241 cases and 13,203 controls that examined the association between RAD51 135G>C polymorphism and breast cancer. No significant association of RAD51 135G>C polymorphism with breast cancer was found in overall and European populations. However, after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded, we observed an overall significant increased breast cancer risk (for the recessive model CC vs. GG/CG: OR = 1.35, 95% CI = 1.05-1.74, P (heterogeneity) = 0.06). In summary, our meta-analysis suggested the RAD51 135G > C polymorphism may contribute to breast cancer susceptibility.

The polymorphism of cytochrome P4501B1 (CYP1B1) codon 432 (rs1056836, CYP1B1*3, or Leu432Val) is thought to have a significant effect on lung cancer risk, but the results are inconsistent. In this meta-analysis, we assessed 9 published studies involving 6501 subjects that investigated the association between the CYP1B1 codon 432 polymorphism and risk of lung cancer. Overall, the CYP1B1 Leu/Val and Val/Val-variant genotypes were associated with a significantly increased risk of lung cancer in different genetic models (heterozygote comparison: OR=1.22; 95% CI=1.02-1.45, P(heterogeneity)=0.068; homozygote comparison: OR=1.41; 95% CI=1.08-1.85, P(heterogeneity)=0.071; dominant model comparison: OR=1.26; 95% CI=1.04-1.51, P(heterogeneity)=0.019; and recessive model comparison: OR=1.17; 95% CI=1.02-1.34, P(heterogeneity)=0.429). In the stratified analysis by ethnicity, significantly increased risks were found among Caucasians for Leu/Val vs Leu/Leu (OR=1.30; 95% CI=1.03-1.64; P(heterogeneity)=0.092), and dominant model (OR=1.35; 95% CI=1.03-1.77; P(heterogeneity)=0.015). However, no significant associations were found in both Europeans and African-Americans for all genetic models. In the subgroup analyses by smoking status, a significantly increased risk of lung cancer was found among smokers (dominant model: OR=1.46; 95% CI=1.08-1.83; P(heterogeneity)=0.175). However, we did not find any statistically significant association by subgroup analyses of pathological type. This meta-analysis suggests that the CYP1B1 Val allele is a low-penetrant risk factor for developing lung cancer.

The estrogen signal is mediated by the estrogen receptor (ER). The specific role of ER-beta, a second ER, in breast carcinogenesis is not known. A number of association studies have been carried out to investigate the relationship between polymorphic sites in the ESR2 gene and breast cancer risk, however, the results are inconsistent. We searched PubMed, Medline, and Web of Science database (updated to 10 January 2010) and identified 13 relevant case-control studies, and approximately 28 single-nucleotide polymorphisms (SNPs) and one micro-satellite marker were reported in the literature. The median number of study subjects was 776 (range 158-13,550). Three genetic variants [(CA)n, rs2987983, and rs4986938] showed significant overall associations with breast cancer, and rs4986938 was reported twice. Because rs4986938 and rs1256049 were the most extensively studied polymorphisms, we subsequently conducted a meta-analysis to evaluate their relationship with breast cancer risk (9 studies of 10,837 cases and 16,021 controls for rs4986938; 8 studies of 11,652 cases and 15,726 controls for rs1256049). For rs4986938, the women harboring variant allele seemed to be associated with a decreased risk either in the dominant model [pooled OR = 0.944, 95% confidence interval (95% CI) 0.897-0.993, fixed-effects] or in the co-dominant model (AG vs. GG) (OR = 0.944, 95% CI 0.895-0.997, fixed-effects). rs1256049 was not associated with breast cancer risk in any model. Five studies had investigated the effect of haplotypes in the ESR2 gene on breast cancer risk, and four of them had positive outcomes. In summary, the present systematic review suggests that SNP rs4986938 as well as haplotypes in the ESR2 gene might be associated with breast cancer. The need for additional studies examining these issues seems of vital importance.