Integrated transcriptomic and proteomic analyses reveal the effects of chronic benzene exposure on the central nervous system in mice.

Benzene exposure is known to cause serious damage to the human hematopoietic system. However, recent studies have found that chronic benzene exposure may also cause neurological damage, but there were few studies in this issue. The aim of this study was to investigate the mechanism of damage to the central nervous system (CNS) by chronic benzene exposure with a multi-omics analysis. We established a chronic benzene exposure model in C57BL/6J mice by gavage of benzene-corn oil suspension, identified the differentially expressed proteins (DEPs) and differentially expressed genes (DEGs) in mice brain using 4D Label-free proteomic and RNA-seq transcriptomic. We observed that the benzene exposure mice had a significant loss of body weight, reduction in complete blood counts, abnormally high MRI signals in brain white matter, as well as extensive brain edema and neural demyelination. 162 DEPs were identified by the proteome, including 98 up-regulated and 64 down-regulated proteins. KEGG pathway analysis of DEPs showed that they were mainly involved in the neuro-related signaling pathways such as metabolic pathways, pathways of neurodegeneration, chemical carcinogenesis, Alzheimer disease, and autophagy. EPHX1, GSTM1, and LIMK1 were identified as important candidate DEGs/DEPs by integrated proteomic and transcriptomic analyses. We further performed multiple validation of the above DEGs/DEPs using fluorescence quantitative PCR (qPCR), parallel reaction monitoring (PRM), immunohistochemistry, and immunoblotting to confirm the reliability of the multi-omics study. The functions of these DEGs/DEPs were further explored and analyzed, providing a theoretical basis for the mechanism of nerve damage caused by benzene exposure.

Comparing ChatGPT's and surgeon's responses to thyroid-related questions from patients.

BACKGROUND: For some common thyroid-related conditions with high prevalence and long follow-up times, ChatGPT can be used to respond to common thyroid-related questions. In this cross-sectional study, we assessed the ability of ChatGPT (version GPT-4.0) to provide accurate, comprehensive, compassionate, and satisfactory responses to common thyroid-related questions. STUDY DESIGN: First, we obtained 28 thyroid-related questions from the Huayitong app, which together with the two interfering questions eventually formed 30 questions. Then, these questions were responded to by ChatGPT (on July 19, 2023), junior specialist and senior specialist (on July 20, 2023) separately. Finally, 26 patients and 11 thyroid surgeons evaluated those responses on four dimensions: accuracy, comprehensiveness, compassion, and satisfaction. RESULTS: Among the 30 questions and responses, ChatGPT's speed of response was faster than that of the junior specialist (8.69 [7.53-9.48] vs. 4.33 [4.05-4.60], P <.001) and senior specialist (8.69 [7.53-9.48] vs. 4.22 [3.36-4.76], P <.001). The word count of the ChatGPT's responses was greater than that of both junior specialist (341.50 [301.00-384.25] vs. 74.50 [51.75-84.75], P <0.001) and senior specialist (341.50 [301.00-384.25] vs. 104.00 [63.75-177.75], P <0.001). ChatGPT received higher scores than junior specialist and senior specialist in terms of accuracy, comprehensiveness, compassion and satisfaction in responding to common thyroid-related questions. CONCLUSIONS: ChatGPT performed better than junior specialist and senior specialist in answering common thyroid-related questions, but further research is needed to validate the logical ability of the ChatGPT for complex thyroid questions.

Effects of miR-330-3p on Invasion, Migration and EMT of Gastric Cancer Cells by Targeting PRRX1-Mediated Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: miRNA, as a biological marker, had more and more attention in recent years due to the important role it plays in cancer. Currently, there are extensive studies on miRNAs, among which miR-330-3p is reported to be implicated in the pathophysiological processes of various cancers. However, little progress has been made in the mechanism of miR-330-3p in gastric cancer. OBJECTIVE: To explore the expression and relevant mechanism of miR-330-3p and PRRX1 in gastric cancer (GC). METHODS: Forty-five GC patients (study group), from whom paired GC and paracancerous tissues were collected, and another 45 healthy subjects (control group) who underwent physical examination during the same period were enrolled. In addition, GC cells and human gastric mucosa cells were purchased, and miR-330-3p-mimics, miR-330-3p-inhibitor, miR-NC, si-PRRX1, and sh-PRRX1 were transfected into MKN45, SGC7901 cell. QRT-PCR was employed to assess the miR-330-3p and PRRX1 expressions in the samples, and the cell expressions of PRRX1, GSK-3ß, p-GSK-3ß, ß-catenin, p-ß-catenin, cyclin D1, N-cadherin, E-cadherin and vimentin were evaluated by Western blot (WB). MTT, Transwell and wound-healing experiments were adopted to detect cell proliferation, invasion and migration. RESULTS: MiR-330-3p was under-expressed, while PRRX1 was highly expressed in the serum of patients, both of which had an area under the curve (AUC) of more than 0.9. MiR-330-3p and PRRX1 were associated with tumor diameter, TNM staging, lymph node metastasis and differentiation of GC patients. Overexpression of miR-330-3p and inhibition of PRRX1 expression could suppress epithelial-mesenchymal transition (EMT), proliferation, invasion and apoptosis of cells. What is more, WB assay showed that overexpressed miR-330-3p and inhibited PRRX1 could inhibit the expression levels of p-GSK-3ß, ß-catenin, cyclin D1, N-cadherin and vimentin proteins, while elevating GSK-3ß, p-ß-catenin and E-cadherin protein expressions. Dual-luciferase reporter assay confirmed that there was a targeting relation between miR-330-3p and PRRX1. Furthermore, rescue experiments revealed that the cell proliferation, invasion, migration did not differ significantly between co-transfected miR-330-3p-mimics+sh-PRRX1, miR-330-3p-inhibitor+si-PRRX1 groups of MKN45 and SGC7901 and the miR-NC group (without transfected sequences). CONCLUSION: Overexpressed miR-330-3p can promote cell EMT, proliferation, invasion and apoptosis through inhibiting PRRX1-mediated Wnt/ß-catenin signaling pathway, which is expected to be a potential therapeutic target for GC.

[Expression of PTEN in Myocardial Tissue in Coronary Heart Disease].

OBJECTIVE: To observe the expression of phosphatase and tensin homology deleted on chromosome ten (PTEN) in myocardial tissue in patients with coronary heart disease, and explore the relevance between the expression of PTEN and the occurrence and development of coronary heart disease. METHODS: A total of 16 death cases with pathological diagnosis of coronary heart disease were collected as experimental group, and 19 cases without myocardial lesions were selected as control group. The expression of PTEN protein and its mRNA were detected by immunohistochemistry and real-time fluorescence quantitative PCR respectively. The correlation between the expression of PTEN and the pathogenesis of coronary heart disease was analyzed. RESULTS: The expression of PTEN protein in myocardium in cases with coronary heart disease was significantly lower compared with the control group (P < 0.05). There was no statistical difference of the expression of PTEN mRNA between experimental and control group (P > 0.05). CONCLUSION: PTEN may be involved in the occurrence and development of coronary heart disease.

Pri-miR-34b/c rs4938723 polymorphism is associated with a decreased risk of gastric cancer.

Previous studies have demonstrated that miR-34 family members are abnormally expressed in gastric cancer. Overexpression of the miR-34 family suppresses gastric carcinogenesis, whereas downregulation of the miR-34 family promotes tumorigenesis. p53 can bind to the promoter region of miR-34b/c, leading to an increase of miR-34b/c expression. Recently, a variant in the promoter region of pri-miR-34b/c (rs4938723) has been discovered, with the function of altering the binding efficiency of transcription factor GATA. The purpose of this study was to examine the role of the miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms in the susceptibility of gastric cancer. We analyzed the distribution of the two polymorphisms in 197 patients with gastric cancer and 289 age-, gender-, ethnicity-, and living area-matched controls using polymerase chain reaction-restriction fragment length polymorphism and DNA direct sequencing. We found that the CT and CT/CC genotypes of the miR-34b/c rs4938723 were associated with a significantly decreased risk of gastric cancer compared with the TT genotype (CT vs. TT: odds ratio [OR]=0.66; 95% confidence interval [95% CI], 0.45-0.97; and CT/CC vs. TT: OR=0.67; 95% CI, 0.47-0.97, respectively). Combined analysis showed that subjects carrying the miR-34b/c rs4938723 CT/CC and TP53 CG/CC genotypes had a 0.62-fold decreased risk to develop gastric cancer compared with subjects carrying the miR-34b/c rs4938723 TT and TP53 CG/CC genotypes (OR=0.62; 95% CI, 0.40-0.96). These findings suggest that the miR-34b/c rs4938723 may individually and jointly have a protective effect on the risk of gastric risk.

Lack of association between let-7 binding site polymorphism rs712 and risk of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is characterized by its highly invasive and metastatic features. Therefore, screening genetic biomarkers of NPC to achieve early diagnose would be of great value for NPC therapy. Single nucleotide polymorphisms in let-7 miRNA binding site in 3' untranslated region of KRAS mRNA have been found to be associated with various cancer risks. In this study, we genotyped the frequency of KRAS rs712 to test its effect on NPC risk in a hospital-based case-control study in a Chinese population, with 188 histologically confirmed NPC patients and 356 cancer-free controls, using polymerase chain reaction-restriction fragment length polymorphism assay. There was no significant difference in the genotype and allele frequencies of the rs712 polymorphism between the NPC patients and the control group (GT vs. GG, OR 0.83, 95% CI 0.57-1.21; TT vs. GG, OR 1.27, 95% CI 0.58-2.75). Our data suggest that the KRAS rs712 polymorphism in let-7 miRNA binding site has no association with NPC risk. Further experiments with larger sample size or other polymorphism sites are needed to verify the result, especially in different ethnic groups.

A let-7 KRAS rs712 polymorphism increases colorectal cancer risk.

Growing evidence has indicated that polymorphism present in the miRNA binding site of target gene can alter the ability of miRNAs to bind its target gene and modulate the development and progression of cancer. We aimed to investigate the association between let-7 KRAS rs712 polymorphism and the risk of colorectal cancer (CRC). The let-7 KRAS rs712 was analyzed in a case-control study, including 339 CRC patients and 313 age- and sex-matched controls; the relationship between the polymorphism and the clinicopathological features of CRC was also examined. Individuals carrying the let-7 KRAS rs712 TT genotype and T allele had an increased risk of developing CRC (TT vs. GG, adjusted OR = 2.18; 95% CI, 1.00-4.77; T vs. G, adjusted OR = 1.50; 95% CI, 1.15-1.96). Stratified analyses revealed that CRC patients with the let-7 KRAS rs712 TT genotype were more likely to have clinical stage III or IV disease (OR = 3.29, 95% CI, 1.32-8.20) and distant metastasis (OR = 4.70, 95% CI, 1.81-12.25). These findings provide evidence that the let-7 KRAS rs712 polymorphism may play crucial roles in the etiology of CRC.

Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk of colorectal cancer.

BACKGROUND: Genome-wide association studies have identified that genetic variants in 8q24 confer susceptibility to colorectal cancer (CRC). Recently, a novel lncRNA (PRNCR1) that located in the 8q24 was discovered. Single nucleotide polymorphisms (SNPs) in the lncRNAs may influence the process of splicing and stability of mRNA conformation, resulting in the modification of its interacting partners. We hypothesized that SNPs in the lncRNA PRNCR1 may be related to the risk of CRC. METHODS: We conducted a case-control study and genotyped five tag SNPs in the lncRNA PRNCR1 in 908 subjects including 313 cases with CRC and 595 control subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: In overall analyses, we found that the rs13252298 and rs1456315 were associated with significantly decreased risks of CRC. In stratification analyses, we found that CRC patients carrying the rs1456315G were likely to have a tumor size of greater than 5 cm (G vs. A: adjusted OR = 1.56, 95% CI: 1.10-2.23). Additionally, patients with the rs7007694C and rs16901946G had decreased risks to develop poorly differentiated CRC, whereas patients with the rs1456315G had an increased risk to develop poorly differentiated CRC. CONCLUSION: These findings suggest that SNPs in the lncRNA PRNCR1 may contribute to susceptibility to CRC.

A let-7 binding site polymorphism rs712 in the KRAS 3' UTR is associated with an increased risk of gastric cancer.

Recently, single nucleotide polymorphisms in let-7 miRNA binding site in 3' untranslated region (UTR) of KRAS mRNA have been found to be associated with the cancer risk. In this study, we genotyped the frequency of KRAS rs712 to test its effect on gastric cancer (GC) risk in a hospital-based case-control study in a Chinese population, with 181 histologically confirmed GC patients and 674 cancer-free controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The TT genotype of rs712 was associated with an increased risk of GC when taking GG genotype as a reference (adjusted odds ratio (OR) = 3.05, 95 % confidence interval (CI), 1.53-6.08). Similarly, the T allele of rs712 was associated with a statistically significant increase in susceptibility compared with G allele (adjusted OR = 1.44, 95 % CI, 1.10-1.90). Our data demonstrated that the T allele of the let-7 binding site polymorphism rs712 in KRAS 3' UTR was associated with a significantly increased risk of GC, suggesting that the KRAS rs712 polymorphism may be a genetic marker for the development of GC.

Association between polymorphisms in the promoter region of miR-143/145 and risk of colorectal cancer.

Emerging evidence suggests that down-regulated miRNAs play an important role in the carcinogenesis of colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) in the promoter region of miRNAs may disturb miRNAs processing, alter their expression, and ultimately affect an individual's susceptibility to CRC. We conducted a case-control study and analyzed twelve SNPs in the promoter region of miR-143/145 of 525 subjects including 242 cases with CRC and 283 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The mutant genotypes or alleles of rs41291957, rs353292, rs353293, and rs4705341 were significantly associated with an increased risk of CRC compared with the wild genotypes or alleles, while rs4705343, rs17796757, rs3733845, and rs3733846 were significantly associated with a decreased risk of CRC. When stratification analysis was done by different variables, such as tumor size, tumor site, differentiated status, clinical stage, and metastasis status, we found that patients with the mutant allele of rs41291957 had an increased risk to develop a tumor size larger than 5 cm. These findings suggest that SNPs in the promoter region of miR-143/145 may be related to the etiology of CRC. However, further larger studies with different ethnic origins are needed to confirm our results due to limited sample sizes in the study.

Association of angiotensin-converting enzyme insertion/deletion polymorphism (rs4646994) with the risk of primary intracerebral hemorrhage.

BACKGROUND: Evidence has suggested that angiotensin-converting enzyme (ACE) may be involved in the etiology of primary intracerebral hemorrhage (PICH), but the underlying association between ACE I/D (rs4646994) polymorphism and PICH risk is still ambiguous. This meta-analysis was performed to quantitatively summarize the evidence for such a relationship. METHODS: Eligible studies were identified by searching PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBM (Chinese biomedical literature database), and WANFANG databases within a range of published years from 1990 to August 2012. The odds ratio (OR) corresponding to the 95% confidence interval (CI) was used to assess the different associations. RESULTS: A total of 28 studies with 2806 cases and 3612 controls were included in this meta-analysis. The pooled examination displayed an overall increased PICH risk associated with ACE I/D polymorphism in a recessive model (OR = 1.80, 95% CI = 1.39-2.33, P < 0.001 for DD versus ID/II), however, this association was only present in Asians (OR = 1.91, 95% CI = 1.45-2.51, P < 0.001) and not in Caucasians (OR = 1.16, 95% CI = 0.55-2.44, P = 0.69). Hypertensive intracerebral hemorrhage (HICH) had a much greater risk (OR = 4.26, 95% CI = 2.87-6.32, P < 0.001) than general PICH (OR = 1.65, 95% CI = 1.25-2.18, P < 0.001) in Asians, and subgroup with controls excluding hypertension had a greater risk (OR = 2.65, 95% CI = 1.78-3.95, P < 0.001) than that including hypertension (OR = 1.50, 95% CI = 1.12-2.02, P = 0.01). CONCLUSIONS: This meta-analysis suggests that DD homozygote of ACE I/D polymorphism has an increased PICH risk in Asians, and may have a synergistic effect with hypertension.

Lack of association between TNFα rs1800629 polymorphism and schizophrenia risk: a meta-analysis.

Evidence has suggested that tumour necrosis factor α (TNFα) may be involved in the aetiology of schizophrenia, but the underlying association between TNFα-308G/A polymorphism (rs1800629) and schizophrenia risk is still ambiguous. This meta-analysis was performed to quantitatively summarise the evidence for such a relationship. Eligible studies were identified by searching PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBM (Chinese Biomedical Literature Database) and WANFANG databases within a range of published years from 1990 to July 2012. The odds ratio (OR) corresponding to the 95% confidence interval (CI) was used to assess the different associations. Twenty-one studies with 4340 cases and 5745 controls were included in this meta-analysis. The pooled examination displayed that there was no significant association between TNFα-308G/A polymorphism and susceptibility to schizophrenia overall (OR=1.047, 95% CI=0.876-1.253, P=0.614 for A vs. G), and no difference in Caucasian subgroup (OR=1.041, 95% CI=0.815-1.331, P=0.747) and Asian subgroup (OR=1.057, 95% CI=0.807-1.386, P=0.686). Lack of association was also found in males (OR=0.862, 95% CI=0.413-1.797, P=0.692) and females (OR=0.797, 95% CI=0.579-1.097, P=0.163) with a dominant model. Taken together, this meta-analysis suggests that TNFα-308G/A polymorphism may not be associated with schizophrenia susceptibility.

A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer.

The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs TP53-mediated cell death, while overexpression of miR-34 induces apoptosis. A potentially functional polymorphism (i.e., rs4938723T/C) in the promoter region of pri-miR-34b/c was predicted to influence the GATA-X binding sites. We aimed to investigate the association between miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of CRC. We genotyped the two polymorphisms in 347 CRC patients and 488 healthy controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assay. We found that the CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of CRC compared with the TT genotype and T allele (CC vs. TT: adjusted OR=0.56; 95% CI, 0.34-0.91; C vs. T: adjusted OR=0.78; 95% CI, 0.64-0.97). In combined analysis, a borderline significance was also observed in subjects carrying the rs4938723 CT/CC and TP53 GG genotypes (adjusted OR=0.66; 95% CI, 0.43-0.99). These findings indicate that the rs4938723 in the promoter region of pri-miR-34b/c was a protective factor for the development of CRC. As the significance is marginal, further replication studies are warranted to confirm these results.

Interactions of interleukin-12A and interleukin-12B polymorphisms on the risk of intracranial aneurysm.

Several lines of evidence indicate that inflammatory processes play pivotal role in the development of intracranial aneurysm (IA). Recently, polymorphisms in the interleukin-12 (IL-12) gene were shown to be associated with immune-mediated inflammatory disease. The aim of this study was to investigate the interactions of IL-12A and IL-12B polymorphisms on the risk of IA in a Chinese population. A total of 422 individuals (including 164 patients with IA and 258 controls) were involved in the study. The polymorphisms (i.e., rs2243115 and rs568408 in IL-12A and rs3212227 in IL-12B) were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay and DNA sequencing. We found an association of the AC/CC genotypes and C allele of IL-12B rs3212227 with an increased risk of IA, compared with the AA genotype and A allele (AC/CC vs. AA: OR = 2.09, 95 % CI: 1.29-3.38; C vs. A: OR = 1.45, 95 % CI: 1.10-1.91). Moreover, a significant gene interaction of IL-12A and IL-12B was evident on the risk of IA, and subjects carrying variant genotypes of IL-12B rs3212227 had an increased risk of IA. In the stratified analysis by gender, the IL-12B rs3212227 AC/CC genotypes had an increased risk of IA compared with the AA genotype in male patients (AC/CC vs. AA: OR = 4.63, 95 % CI: 1.92-11.16). These findings suggest that the IL-12A and IL-12B independently and jointly be involved in the susceptibility to IA.

No association between ACE polymorphism and risk of nasopharyngeal carcinoma.

Emerging evidence has shown that angiotensin I-converting enzyme (ACE) plays pivotal roles not only in the regulation of cardiovascular homeostasis but also in the process of tumorigenesis. A common ACE I/D polymorphism has been found to be functional, with the D allele displaying a higher plasma ACE level and ACE activity. The purpose of this study was to investigate whether the ACE I/D polymorphism was related to the risk of nasopharyngeal carcinoma (NPC). The study included 175 patients with NPC and 279 age- and sex-matched control subjects. The ACE I/D polymorphism was identified by a polymerase chain reaction analysis. No association was found between the ACE I/D polymorphism and risk of NPC (ID vs. II: odds ratio [OR] = 0.77, 95% confidence interval [CI] 0.51-1.17; DD vs. II: OR = 0.98, 95%CI 0.56-1.72, respectively). This finding indicates that the ACE I/D polymorphism may not play a role in susceptibility to NPC. Further studies are warranted to confirm this finding, especially in ethnically disparate populations.

The association between MLH1 -93 G>A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysis.

DNA mismatch repair, known as a fundamentally biological pathway, plays key roles in maintaining genomic stability, eliminating mismatch bases and preventing both mutagenesis in the short term and cancerogenesis in the long term. Polymorphisms of MLH1 in individuals may have an effect on the DNA repair capacity and therefore on cancer risk. Recently, emerging studies have been done to evaluate the association between MLH1 -93 G/A polymorphism and cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. In this meta-analysis, we assessed reported studies of association between the MLH1 -93 G/A polymorphism and cancer risk including 13 691 cancer cases and 14 068 controls from 17 published studies. A borderline significant association between the MLH1 -93 G/A polymorphism and cancer risk was observed in overall analysis [heterozygote: odds ratio (OR) = 1.15; 95% confidence interval (CI) 1.05-1.26; homozygote: OR = 1.21; 95% CI, 1.04-1.40; dominant model: OR = 1.13; 95% CI 1.01-1.26; recessive model: OR = 1.21; 95% CI 1.07-1.35, respectively]. In subgroup analysis by ethnicity, significantly increased risks were found in Asian population and mixed population but not in Caucasian population. After stratified analysis according to the quality of literature, increased cancer risks were observed in the studies of lower quality but not in the studies of higher quality. Similarly, elevated cancer risks were observed in hospital-based studies but not in population-based studies. These findings showed no persuasive evidence that MLH1 -93 G/A polymorphism was associated with an increased risk of cancer. On the conservative standpoint, well-designed population-based studies with larger sample size in different ethnic groups should be performed to further confirm these results.

Null genotypes of GSTM1 and GSTT1 contribute to risk of cervical neoplasia: an evidence-based meta-analysis.

BACKGROUND AND OBJECTIVES: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens. METHODS: In this meta-analysis, twenty-five studies were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases: 23 evaluated GSTM1 and 19 evaluated GSTT1. Crude odds ratios with corresponding 95% confidence intervals were used to estimate the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Subgroup analyses were conducted by pathological history, ethnicity, source of DNA for genotyping, quality score, and matching variable. RESULTS: The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia (for GSTM1: OR = 1.40; 95%CI, 1.19-1.65; for GSTT1: OR = 1.30; 95%CI, 1.05-1.62, respectively). Subgroup analyses showed that the null genotype of GSTM1 increased the risk of cervical neoplasia in Asians, studies with DNA isolation from white blood cells and tissue samples, both high and low quality studies, and matched studies. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia (OR = 1.72; 95%CI, 1.18-2.51). CONCLUSION: These findings indicate that GSTM1 and GSTT1 polymorphisms, particularly GSTM1-GSTT1 interaction, may play critical roles in the development of cervical neoplasia. A conservative manner should be adopted to interpret these results because of obvious heterogeneity between-study, unadjusted data, and relatively small sample size in this meta-analysis. Well designed studies with larger sample size are of great value to confirm these results.

The association between two polymorphisms in pre-miRNAs and breast cancer risk: a meta-analysis.

Emerging evidence has shown that miRNAs participate in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphism (SNP) which located in the pre-miRNA may affect the processing and then influence the expression of mature miRNA. Previous studies yielded conflicting results as to the association of two common polymorphisms in pre-miRNAs (i.e. hsa-miR-146 rs2910164 and hsa-miR-196a2 rs11614913) with breast cancer. To derive a more precise effect on the association between these polymorphisms and breast cancer risk, we conducted a meta-analysis. Through retrieving PubMed for the period up to May 2010, a total of four studies were identified with 3,007 cases and 3,718 controls for has-miR-146a rs2910164 polymorphism and with 3,287 cases and 4,298 controls for hsa-miR-196a2 rs11614913 polymorphism. We found that individuals carrying CC genotype of has-miR-196a2 rs11614913 polymorphism was associated with an increased breast cancer risk in homozygote comparison (OR = 1.30; 95% CI, 1.01-1.68), and dominant model (OR = 1.11; 95% CI, 1.01-1.23). However, no significant association between has-miR-146a rs2910164 polymorphism and breast cancer risk was observed in all comparison models tested. These findings suggest that has-miR-196a2 rs11614913 polymorphism may play crucial roles in breast cancer development.

RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies.

Growing evidence suggests that RAD51 plays a pivotal role in the repair of DNA double-strand breaks and the maintenance of genomic stability. A single nucleotide polymorphism, 135G/C, has been identified in the 5' untranslated region of the RAD51 gene and has been shown to influence gene transcription activity. Previous studies yielded conflicting results as to the association of 135G/C polymorphism with breast cancer. We aimed to assess the effect of 135G/C of RAD51 on breast cancer susceptibility with the use of a meta-analysis. We performed a meta-analysis of 21 published case-control studies up to April 2010. We found that the CC genotype was associated with a significantly increased risk of breast cancer when compared with the GG, CG, and CG/GG genotypes. Subgroup analyses showed that individuals carrying the CC genotype were associated with an elevated tumor risk in European populations and in sporadic breast cancer. After stratified analyses according to manuscript quality, the CC genotype was associated with a significantly increased risk of breast cancer compared with the CG genotype in studies of both higher and lower quality. However, significantly elevated risk was found in studies of higher quality, but not in studies of lower quality when homozygote and a recessive comparison model were tested. This meta-analysis indicates that RAD51 135G/C polymorphism may be identified as a susceptibility locus for breast cancer.

The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis.

BACKGROUND: Emerging evidence suggests that ataxia telangiectasia-mutated (ATM) is involved in numerous damage repair signaling pathways and cell-cycle checkpoints. Heterozygous carriers of ATM-mutations have an increased risk for the development of breast cancer. The purpose of this study is to evaluate the association between ATM exon39 5557G > A (D1853N, rs1801516) polymorphism and breast cancer susceptibility with the use of a meta-analysis. METHODS: By searching PubMed and Embase databases, a total of 9 epidemiological studies with 4,191 cases and 3,780 controls were identified. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for ATM D1853N polymorphism and breast cancer risk were calculated using fixed- or random-effects model based on the degree of heterogeneity among studies. RESULTS: No significant association between the ATM D1853N polymorphism and breast cancer risk was observed in overall analysis (GA versus GG: OR = 1.18; 95% CI, 0.90-1.53; AA versus GG: OR = 0.77; 95% CI, 0.58-1.03; dominant model: OR = 1.16; 95% CI, 0.89-1.51; and recessive model: OR = 0.78; 95% CI, 0.59-1.04, respectively). CONCLUSION: Our results indicate that ATM D1853N polymorphism is not a risk factor for developing breast cancer.