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RATIONALE AND OBJECTIVES: To investigate the potential of T1-weighted imaging (T1WI)-based hippocampal radiomics as imaging markers for the diagnosis of Alzheimer's disease (AD) and their efficacy in discriminating between mild cognitive impairment (MCI) and dementia in AD. METHODS: A total of 126 AD patients underwent T1WI-based magnetic resonance imaging (MRI) examinations, along with 108 age-sex-matched healthy controls (HC). This was a retrospective, single-center study conducted from November 2021 to February 2023. AD patients were categorized into two groups based on disease progression and cognitive function: AD-MCI and dementia (AD-D). T1WI-based radiomics features of the bilateral hippocampi were extracted. To diagnose AD and differentiate between AD-MCI and AD-D, predictive models were developed using random forest (RF), logistic regression (LR), and support vector machine (SVM). We compared radiomics features between the AD and HC groups, as well as within the subgroups of AD-MCI and AD-D. Area under the curve (AUC), accuracy, sensitivity, and specificity were all used to assess model performance. Furthermore, correlations between radiomics features and Mini-Mental State Examination (MMSE) scores, tau protein phosphorylated at threonine 181 (P-tau-181), and amyloid ß peptide1-42 (Aß1-42) were analyzed. RESULTS: The RF model demonstrated superior performance in distinguishing AD from HC (AUC=0.961, accuracy=90.8%, sensitivity=90.7%, specificity=90.9%) and in identifying AD-MCI and AD-D (AUC=0.875, accuracy=80.7%, sensitivity=87.2%, specificity=73.2%) compared to the other models. Additionally, radiomics features were correlated with MMSE scores, P-tau-181, and Aß1-42 levels in AD. CONCLUSION: T1WI-based hippocampal radiomics features are valuable for diagnosing AD and identifying AD-MCI and AD-D.
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OBJECTIVE: To analyze recurrent factors in patients with clinical early-stage cervical cancer (ESCC) following hysterectomy and adjuvant radiotherapy. METHODS: We collected data from patients with ESCC, staged according to the 2009 Federation International of Gynecology and Obstetrics (FIGO) staging criteria, who underwent hysterectomy followed by adjuvant radiotherapy between 2012 and 2019. These patients were subsequently restaged using the 2018 FIGO criteria. Univariable and multivariable analyses, along with nomogram analyses, were conducted to explore factors associated with recurrence-free survival (RFS). RESULTS: A total of 310 patients met the inclusion criteria, with a median follow-up time of 46 months. Among them, 126 patients with ESCC were restaged to stage III C1 or III C2 after surgery due to lymph node metastasis (LNM) based on the 2018 FIGO staging criteria. Of these, 60 (19.3%) experienced relapse. The 1-, 3-, and 5-year RFS rates were 93.9%, 82.7%, and 79.3%, respectively. Multivariate analysis revealed that the number of positive lymph nodes (LNs), tumor diameter (TD) > 4 cm, and parametrial invasion (PI) were associated with recurrence. The nomogram indicated their predictive value for 3-year and 5-year RFS. Notably, the 5-year recurrence rate (RR) increased by 30.2% in patients with LNM, particularly those with ≥ 3 positive LNs (45.5%). Patients with stage III C2 exhibited a significantly higher RR than those with IIIC1 (56.5% vs. 24.3%, p < 0.001). The 5-year RFS for patients with TD > 4 cm was 65.8%, significantly lower than for those with TD ≤ 4 cm (88.2%). Subgroup analysis revealed higher 5-year RRs in patients with stage III C2 than that in patients with III-C1 (56.5% vs. 24.3%, p < 0.001), demonstrating a significant difference in the RFS survival curve. CONCLUSION: RR in patients with clinical ESCC after hysterectomy followed by adjuvant radiotherapy is correlated with the number of positive LNs, TD > 4 cm, and PI. Emphasis should be placed on the common high-risk factor of LNM association with recurrence after radical hysterectomy in ESCC.
Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Radiotherapy, Adjuvant , Treatment Outcome , Disease-Free Survival , Uterine Cervical Neoplasms/pathology , Neoplasm Staging , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Hysterectomy , Lymph Node ExcisionABSTRACT
In the era of personalized medicine, the introduction of translational studies in clinical trials has substantially increased their costs, but provides the possibility of improving the productivity of trials with a better selection of recruited patients. With the overall goal of creating a roadmap to improve translational design for future gynecological cancer trials and of defining translational goals, a main discussion was held during a brainstorming day of the Gynecologic Cancer InterGroup (GCIG) Translational Research Committee and overall conclusions are here reported. A particular emphasis was dedicated to the new frontier of the immunoprofiling of gynecological cancers. The discussion pointed out that to maximize patients' benefit, translational studies should be integral to clinical trial design with standardization and optimization of procedures including a harmonization program of Standard Operating Procedures. Pathology-reviewed sample collection should be mandatory and ensured by dedicated funding. Biomarker validation and development should be made public and transparent to ensure rapid progresses with positive outcomes for patients. Guidelines/templates for patients' informed consent are needed. Importantly for the public, recognized goals are to increase the involvement of advocates and to improve the reporting of translational data in a forum accessible to patients.
Subject(s)
Consensus , Genital Neoplasms, Female/pathology , Translational Research, Biomedical , Biomarkers, Tumor/metabolism , Clinical Trials as Topic , Female , Humans , Precision MedicineABSTRACT
OBJECTIVE: An improved nerve-sparing radical hysterectomy (NSRH), which is based on the paravesico-vaginal space, has been recently introduced in a phase II, prospective clinical trial by our team. This study aims to report the surgical and oncological outcomes of this improved NSRH. METHODS: One hundred seventy-seven consecutive patients were enrolled in our study and underwent the improved NSRH. The proportion of successful catheter removal and postvoid residual urine volume (PVR) of 50â¯mL or less at postoperative day 7 or day 4 was used to assess surgical outcomes. The local control rate (LCR), disease free survival (DFS), and overall survival (OS) were used to assess oncological outcomes. RESULTS: Postoperative 30-day complications occurred in 27/177 (15.3%) patients. The rate of successful catheter removal and PVR of 50â¯mL or less were 85.2% (23/27) and 66.7% (18/27) at postoperative day 7, and 73.3% (110/150) and 35.3% (53/150) at postoperative day 4. A total of 13 (7.9%) patients showed recurrence after a median follow-up time of 39.2 months (range 3.2-68.1 months). The estimated 2-year and 5-year DFS rates were 92.2% and 91.1%, respectively. Seven (4.2%) patients presented local recurrence, and five (3.0%) patients were dead at the end of the follow-up period. The estimated 5-year LCR and OS were 95.1% and 96.2%, respectively. In univariate analysis, International Federation of Gynecology and Obstetrics (FIGO) stage, lymphovascular space invasion (LVSI), and lymph node metastasis were found to be the prognostic risk factors of DFS. Patients with LVSI were associated with a worse DFS according to the multivariate analysis. CONCLUSIONS: The improved NSRH in our study may provide better surgical outcomes without compromising the survival in patients with early cervical cancer.
Subject(s)
Adenocarcinoma/surgery , Carcinoma, Squamous Cell/surgery , Hysterectomy/mortality , Organ Sparing Treatments , Urinary Bladder/innervation , Urinary Bladder/physiology , Uterine Cervical Neoplasms/surgery , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Prognosis , Prospective Studies , Survival Rate , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathologyABSTRACT
The Xeroderma pigmentosum group G (XPG) gene promotes recognition and excision of damaged DNA during the DNA repair process. We conducted a comprehensive search of the MEDLINE, EMBASE, and Chinese Biomedical databases for publications evaluating the association XPG gene rs751402 C>T polymorphism and overall cancer risk. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were adopted to assess the strength of the association. A total of 22 publications encompassing 10538 cases and 10511 control subjects were included in the final meta-analysis. We found the polymorphism to be associated with increased cancer risk (TT vs. CC: OR = 1.18, 95% CI = 1.01-1.38, P = 0.040; CT vs. CC: OR = 1.12, 95% CI = 1.01-1.24, P = 0.040; and CT/TT vs. CC: OR = 1.12, 95% CI = 1.002-1.26, P = 0.045). Stratification by cancer type indicated that this polymorphism may increase the risk of gastric cancer and hepatocellular carcinoma, which was further confirmed by a false-positive report probability analysis. Genotype-based mRNA expression provides further evidence that this polymorphism is associated with altered XPG mRNA expression. This meta-analysis suggests XPG gene rs751402 C>T polymorphism correlates with overall cancer risk, especially for gastric cancer and hepatocellular carcinoma.
ABSTRACT
The TP53 gene product is an important regulator of cell growth and a tumor suppressor. The association between TP53 Arg72Pro polymorphism and ovarian cancer risk has been widely investigated, but the results are contradictory. We therefore searched the PubMed, EMBASE and Chinese Biomedical databases for studies on the relation between TP53 Arg72Pro polymorphism and ovarian cancer risk. Our final meta-analysis included 24 published studies with 3271 cases and 6842 controls. Pooled results indicated that there was no significant association between TP53 Arg72Pro polymorphism and ovarian cancer risk [Pro/Pro vs. Arg/Arg: odds ratio (OR) =1.04, 95% confidence interval (CI) = 0.81-1.34; Arg/Pro vs. Arg/Arg: OR = 1.14, 95% CI = 0.96-1.36; recessive: OR = 1.05, 95% CI = 0.90-1.22; dominant: OR = 1.12, 95% CI = 0.94-1.33; and Pro vs. Arg: OR = 1.06, 95% CI=0.93-1.20]. Likewise, stratified analyses failed to reveal a genetic association. Despite some limitations, the present meta-analysis provides statistical evidence indicating a lack of association between TP53 Arg72Pro polymorphism and ovarian cancer risk.
ABSTRACT
Inactivation of p53 greatly contributes to serous ovarian cancer, while the role of the wild-type p53 induced phosphatase 1 (Wip1) is quite unclear. In this study, by silencing or overexpression of Wip1, we found that Wip1 suppressed ovarian cancer cell invasion, migration, epithelial to mesenchymal transition (EMT), and ovarian cancer metastasis in xenograft animal models. Mechanistic studies showed that Wip1 may block ovarian cancer metastasis through inhibition of Snail and p-Akt expression because silencing or overexpression of Wip1 either upregulated or downregulated the expression of Snail and p-Akt (Ser 473), while further knockdown of Snail by shRNA or inhibition of p-Akt by a chemical compound attenuated cell invasion, migration and EMT in Wip1 silencing cells. We also found that the phosphorylation of Akt at Ser 473 might be mediated through p-ATM (Ser 1981). Thus, Wip1 may suppress ovarian cancer metastasis through negative regulation of p-ATM, p-Akt, and Snail, which was also evidenced in the limited clinical specimens. Therefore, our data may provide a novel therapeutic indication for serous ovarian cancer based on the uncovered mechanism associated with the precise function of Wip1 independent of p53.
Subject(s)
Ataxia Telangiectasia Mutated Proteins/metabolism , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Protein Phosphatase 2C/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Snail Family Transcription Factors/metabolism , Animals , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Epithelial-Mesenchymal Transition/physiology , Female , Heterografts , Humans , Mice , Neoplasm Invasiveness/pathology , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/metabolism , Signal Transduction/physiologyABSTRACT
The kinesin-like factor 1 B (KIF1B) gene plays an important role in the process of apoptosis and the transformation and progression of malignant cells. Genetic variations in KIF1B may contribute to risk of epithelial ovarian cancer (EOC). In this study of 1,324 EOC patients and 1,386 cancer-free female controls, we investigated associations between two potentially functional single nucleotide polymorphisms in KIF1B and EOC risk by the conditional logistic regression analysis. General linear regression model was used to evaluate the correlation between the number of variant alleles and KIF1B mRNA expression levels. We found that the rs17401966 variant AG/GG genotypes were significantly associated with a decreased risk of EOC (adjusted odds ratio (OR) = 0.81, 95 % confidence interval (CI) = 0.68-0.97), compared with the AA genotype, but no associations were observed for rs1002076. Women who carried both rs17401966 AG/GG and rs1002076 AG/AA genotypes of KIF1B had a 0.82-fold decreased risk (adjusted 95 % CI = 0.69-0.97), compared with others. Additionally, there was no evidence of possible interactions between about-mentioned co-variants. Further genotype-phenotype correlation analysis indicated that the number of rs17401966 variant G allele was significantly associated with KIF1B mRNA expression levels (P for GLM = 0.003 and 0.001 in all and Chinese subjects, respectively), with GG carriers having the lowest level of KIF1B mRNA expression. Taken together, the rs17401966 polymorphism likely regulates KIF1B mRNA expression and thus may be associated with EOC risk in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.
Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Kinesins/genetics , Neoplasms, Glandular and Epithelial/genetics , Ovarian Neoplasms/genetics , Adult , Aged , Alleles , Asian People , Carcinoma, Ovarian Epithelial , Female , Gene Expression Regulation, Neoplastic , Genotype , Humans , Kinesins/biosynthesis , Middle Aged , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Polymorphism, Single Nucleotide , RNA, Messenger/biosynthesis , Risk FactorsABSTRACT
Polymorphisms in Caspase-7 (CASP7) may modulate the programmed cell death and thus contribute to cervical cancer risk. In this case-control study of 1,486 cervical cancer cases and 1,301 controls, we investigated associations between four potentially functional polymorphisms in CASP7 and cervical cancer risk and evaluated their locus-locus interaction effects on the risk. The genotype-phenotype correlation was performed by a generalized linear regression model. We found that the rs4353229 polymorphism was associated with cervical cancer risk (under a recessive model: crude OR = 1.20, 95% CI = 1.02-1.40). Compared with the TT genotype, the rs10787498GT genotype was associated with an increased cervical cancer risk (adjusted OR = 1.19, 95% CI = 1.00-1.41). Combination analysis showed that subjects with four putative risk genotypes had a 1.54-fold increased cancer risk, compared with those who carried three or less putative risk genotypes. We also observed significant locus-locus joint effects on the risk, which may be mediated by the polymorphisms regulating CASP7 mRNA expression. Subsequent multifactor dimensionality reduction and classification and regression tree analyses indicated that the CASP7 genotypes might have a locus-locus interaction effect that modulated cervical cancer risk. Out data suggest that CASP7 polymorphisms may interact to modify cervical cancer risk by a possible mechanism of regulating CASP7 mRNA expression.
Subject(s)
Caspase 7/genetics , Genetic Predisposition to Disease , Uterine Cervical Neoplasms/enzymology , Uterine Cervical Neoplasms/genetics , Alleles , Case-Control Studies , Caspase 7/metabolism , China , Disease Susceptibility , Female , Genetic Association Studies , Genetic Loci , Genotype , Humans , Logistic Models , Odds Ratio , Polymorphism, Single Nucleotide , RNA, Messenger/metabolism , Uterine Cervical Neoplasms/pathologyABSTRACT
The atypical protein kinase C (aPKCι), encoded by the PRKCI gene, has been recently found to be a unique human oncoprotein, compared with some other diverse PKC isozymes. Genetic variations in PRKCI have also been reported to be associated with prostate cancer (PCa) risk in Caucasian populations, but no similar studies have been reported for Chinese populations. We genotyped two well-described PRKCI single nucleotide polymorphisms (SNPs) rs546950 and rs4955720 in 1015 PCa patients and 1044 cancer-free controls of Eastern Chinese men. SNPs in the vicinity of those two variants of PRKCI were evaluated using the in silico analysis. Logistic regression was then used to estimate their associations with and interactions in PCa risk. Although no significant main effects were found for the two tested SNPs in the single locus analysis, individuals carrying homozygote wide-type form of these two SNPs had slightly reduced PCa risk (adjusted OR = 0.63, 95% CI = 0.40-0.99, P = 0.045), compared with those carrying any of heterozygous or homozygous variant genotypes. Our results indicated that the two PRKCI SNPs were jointly associated with PCa risk in an Eastern Chinese population. Larger studies with multiethnic groups are warranted to confirm these findings and to explore the role of PRKCI SNPs in the etiology of PCa.
Subject(s)
Asian People/genetics , Genetic Predisposition to Disease , Isoenzymes/genetics , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/genetics , Protein Kinase C/genetics , Adult , Aged , Aged, 80 and over , Asian People/ethnology , Case-Control Studies , China/ethnology , Computer Simulation , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Polymorphism, Single NucleotideABSTRACT
XRCC4 plays a crucial role in the non-homologous end joining pathway that maintains genome stability. In this two-stage case-control study with 1,764 non-BRCA1/2 breast cancer patients and 1,623 cancer-free controls, we investigated the contribution of genetic variants of XRCC4 to breast cancer susceptibility in Chinese women. We identified a recessive missense variant, rs3734091 (c.739G>T, p.Ala247Ser), of XRCC4 that was significantly associated with an increased risk of breast cancer (odds ratio [OR] = 3.92, P = 0.007), particularly with the risk of developing triple-negative breast cancer (OR = 18.65, P < 0.0001). This p.Ala247Ser variant disturbed the nuclear localization of XRCC4 in cells homozygous for the rs3734091-T allele but not in heterozygous cells at both the cellular and tissue levels. In heterozygous cells, wild-type XRCC4 facilitated the nuclear localization of the XRCC4A247S mutant, thus compensating for the impaired localization of XRCC4A247S. This provided a biological mechanism by which rs3734091 conferred an increased susceptibility to non-BRCA1/2 breast cancer exclusively under a recessive model. Further functional analyses revealed that p.Ala247Ser impaired the DNA damage repair capacity and ultimately perturbed genomic stability. Taken together, our findings document the role of XRCC4 in non-BRCA1/2 breast cancer predisposition and reveal its underlying biological mechanism of action.
Subject(s)
Breast Neoplasms/genetics , DNA-Binding Proteins/genetics , Genetic Predisposition to Disease/genetics , Asian People/genetics , Blotting, Western , Breast Neoplasms/metabolism , Case-Control Studies , Cell Nucleus/metabolism , Comet Assay , DNA Damage , DNA-Binding Proteins/metabolism , Female , Fluorescent Antibody Technique , Genes, BRCA1 , Genes, BRCA2 , Genotype , Humans , Immunohistochemistry , Immunoprecipitation , Polymerase Chain Reaction , Protein Transport , RNA, Small InterferingABSTRACT
Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer (PCa) cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio (OR): 0.66, 95% confidence interval (CI) =0.48-0.92] and increased plasma adiponectin levels (P = 0.036 and 0.043), with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa (P = 6.7 × 10⻳). ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.
Subject(s)
Adiponectin/genetics , Ethnicity , Genetic Predisposition to Disease , Genetic Variation , Adiponectin/blood , Aged , China , Enzyme-Linked Immunosorbent Assay , Humans , Male , Middle Aged , Polymorphism, Single NucleotideABSTRACT
X-ray repair cross complementing 1 (XRCC1) plays a key role in DNA repair, genetic instability and tumorigenesis. A series of epidemiological studies have examined associations between XRCC1 polymorphisms and cervical cancer risk, but the findings remain inconclusive. We searched three electronic databases (MEDLINE, EMBASE and CNKI) for studies on the association between XRCC1 polymorphisms and cervical cancer risk published before June 2013. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated to estimate risk associations. A total of 28 case-control studies from 15 publications with 5,890 cervical cancer cases and 7,626 controls were identified. There was a significant association between rs25487 and cervical cancer risk in Asian populations (Dominant model: OR = 1.25, 95 % CI =1.04-1.50, P = 0.051 for heterogeneity test). After excluding three studies deviated from Hardy-Weinberg equilibrium, we observed a significant association of rs1799782 with cervical cancer risk in all populations and in Asian populations (Recessive model: OR = 1.62 and 1.72, 95 % CI = 1.22-2.14 and 1.29-2.30, P = 0.090 and 0.266 for heterogeneity test, respectively). However, there was no significant association between rs25489 and cervical cancer risk. These findings were further confirmed by false-positive report probability analysis. No publication bias was found by using the funnel plot and Egger's test. This meta-analysis provides strongly statistical evidence for the association between rs1799782 and cervical cancer risk, as well as its association with rs25487 only in Asian populations. However, single large, well-designed prospective studies are needed to confirm these findings.
Subject(s)
DNA-Binding Proteins/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Uterine Cervical Neoplasms/genetics , Asian People/genetics , Case-Control Studies , DNA Repair/genetics , Female , Humans , Polymorphism, Single Nucleotide , Risk , Uterine Cervical Neoplasms/pathology , White People , X-ray Repair Cross Complementing Protein 1ABSTRACT
BACKGROUND: Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations. METHODS: We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities. RESULTS: The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity. CONCLUSIONS: Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.
Subject(s)
Leptin/genetics , Neoplasms/genetics , Polymorphism, Single Nucleotide , Prostatic Neoplasms/genetics , RNA, Messenger/genetics , Receptors, Leptin/genetics , Case-Control Studies , Databases, Bibliographic , Genetic Predisposition to Disease , HapMap Project , Humans , Male , Models, Genetic , Neoplasms/ethnology , Prostatic Neoplasms/ethnology , Racial GroupsABSTRACT
BACKGROUND: Transforming growth factor-beta 1 (TGF-ß1) protein may be multifunctional and related to the development of fibrosis, induction of apoptosis, extracellular signaling and inhibition of proliferation in response to radiation-induced DNA damage. Several studies have investigated associations between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late radiation-induced injury of normal tissue, but the conclusions remain controversial. METHODS: We searched three electronic databases (i.e., MEDLINE, EMBASE and EBSCO) for eligible publications and performed a meta-analysis assessing the association of three commonly studied SNPs in TGFB1 (i.e., rs1800469, rs1800470 and rs1800471) with risk of late radiation-induced injury of normal tissue. RESULTS: We finally included 28 case-only studies from 16 publications on aforementioned SNPs in TGFB1. However, we did not find statistical evidence of any significant association with overall risk of late radiotherapy toxicity in the pooled analysis or in further stratified analysis by cancer type, endpoint, ethnicity and sample size. CONCLUSIONS: This meta-analysis did not find statistical evidence for an association between SNPs in TGFB1 and risk of late radiation-induced injury of normal tissue, but this finding needs further confirmation by a single large study.
Subject(s)
Polymorphism, Single Nucleotide , Radiation Injuries/genetics , Radiotherapy/adverse effects , Transforming Growth Factor beta1/genetics , Genetic Predisposition to Disease/genetics , Humans , Time FactorsABSTRACT
BACKGROUND: Caspase 7 (CASP7) is an important regulator and executioner in the apoptosis pathway and plays a crucial role in cancer development and progression. However, few studies have evaluated associations between functional single nucleotide polymorphisms (SNPs) in the 3' untranslational region (UTR) of CASP7 and risk of gastric cancer. METHODS: In a case-control study of 1117 patients with gastric cancer and 1146 cancer-free controls with frequency matching on age and sex, we genotyped four potentially functional SNPs (rs4353229T>C, rs10787498T>G, rs1127687G>A and rs12247479G>A) located in the microRNA binding sites of the CASP7 3' UTR by using Taqman assays and evaluated their associations with risk of gastric cancer by using logistic regression analyses as well as multifactorial dimension reduction (MDR) analysis. RESULTS: In the single-locus analysis, only the CASP7 rs4353229 TT genotype was associated with 0.83-fold decreased risk (95% confidence interval [CI] = 0.70-0.98) of gastric cancer under a recessive model, compared with the CT/CC genotypes. In the combined analysis of all four SNPs, we found that the risk of gastric cancer decreased by 19% in those carrying any of the risk genotypes (adjusted odds ratio = 0.81, 95% CI = 0.68-0.96), compared with those carrying zero risk genotypes, and this risk was more evident in subgroups of younger age (<59 years), females, non-smokers, non-drinkers and patients with non-gastric cardia adenocarcinoma. Further MDR analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer. CONCLUSIONS: Potentially functional CASP7 variants may contribute to risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.
Subject(s)
Adenocarcinoma/genetics , Asian People/genetics , Caspase 7/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Stomach Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Cell Line, Transformed , China , Female , Gene Frequency , Gene Order , Genotype , Humans , Linkage Disequilibrium , Male , Middle Aged , Prognosis , RNA, Messenger/genetics , Young AdultABSTRACT
BACKGROUND: The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis. CONCLUSIONS/SIGNIFICANCES: In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted ORâ=â1.42 (1.13-1.78), Pâ=â0.003 and 1.29 (1.07-1.55), Pâ=â0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted ORâ=â0.76 (0.64-0.92), Pâ=â0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted ORâ=â1.24 (1.04-1.47), Pâ=â0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies.
Subject(s)
Polymorphism, Single Nucleotide , Prostatic Neoplasms/genetics , TOR Serine-Threonine Kinases/genetics , Aged , Asian People/genetics , Asian People/statistics & numerical data , Case-Control Studies , China/epidemiology , Gene Frequency , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Prostatic Neoplasms/epidemiology , RiskABSTRACT
BACKGROUND: High risk human papillomavirus (HPV) infection is the major cause of cervical cancer. Several epidemiological studies have performed HPV screening in Chinese women, but no report was for Shanghai suburb women. OBJECTIVES: To understand the prevalence of HPV infection and risk factors in Shanghai suburbs. STUDY DESIGN: Between March 2011 and May 2011, 10,000 female volunteers lived in Fengxian District of Shanghai were recruited for the detection of 21 HPV types using PCR and fast flow hybridization of gene chip array. For the 508 HPV-positive patients, we performed the liquid-based ThinPrep cytology test (TCT) and histological examination for the diagnosis of local cervical lesions. The questionnaire surveyed demographic and behavioral indicators for the evaluation of risk factors of HPV infection. RESULTS: We found that the HPV-positive rate was 12.6%. The five top HPV types were as follows (in descending order): HPV52, 16, 58, 18 and 33. Moreover, HPV-positive rates were higher in women with older age, lower educational level, younger age of the first sexual intercourse, multiple sexual partners, no usage of condom for contraception, multiple deliveries, vaginal delivery, menopause, vaginal inflammation, cervical erosion and no regular cervical cytological examination. We also found that an HPV genotyping in combination with TCT and histological examination could improve early diagnosis for local cervical lesions. CONCLUSION: HPV infection was associated with age, sexual behavior and chronic inflammation of the cervix and vagina. We recommend popularizing HPV genotyping in women with high risk factors for the early diagnosis and prevention of cervical cancer.
Subject(s)
Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , China/epidemiology , Female , Humans , Microarray Analysis , Middle Aged , Nucleic Acid Hybridization , Oligonucleotide Array Sequence Analysis , Papillomaviridae/classification , Papillomaviridae/genetics , Polymerase Chain Reaction , Prevalence , Risk Factors , Suburban Population , Surveys and Questionnaires , Young AdultABSTRACT
DNA Polymerase ζ (Polζ), an error-prone DNA polymerase involved in translesion DNA synthesis, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of several cancers. To evaluate the association of Polζ with chemoradiation resistance and prognosis in cervical cancer, we enrolled 123 patients with squamous cell carcinoma of cervical cancer, who had adjuvant concurrent chemoradiation therapy after radical surgery treated at Fudan University Shanghai Cancer Center between 2008 and 2009, and tested their in vitro tumor inhibition rates using the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide method and Polζ protein expression in paraffin-embedded tissues using immunohistochemistry. We found that the Polζ-positive expression was detected in 22 % of the cases. The median in vitro inhibition rate of tumor cell growth by cisplatin, carboplatin, nedaplatin, and oxaliplatin was 80, 37, 78, and 51 %, respectively. Among the tumor-related variables, FIGO stage, tumor grade, and Polζ protein expression (adjusted HR 6.7, 4.2 and 6.7; 95 % CI 1.7-26.3, 1.0-17.3 and 1.8-25.4; P = 0.007, 0.046 and 0.005, respectively) were found to be significant predictors for recurrence. Kaplan-Meier survival estimates showed that the patients with more advanced stage (IIB) or Polζ-positive expression had a significantly shorter progression-free survival. Polζ-positive expression was significantly associated with depth of cervical stromal invasion (P = 0.012). However, the association between Polζ expression and in vitro tumor inhibition rates was not significant. Taken together, Polζ expression can be used as the predictor for poor prognosis, which might be caused by the potential chemoradiation resistance of the cervical cancer patients. The mechanism deserves further exploration.