Prediction of recurrence-related factors for patients with early-stage cervical cancer following radical hysterectomy and adjuvant radiotherapy.

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.

Two novel PRKCI polymorphisms and prostate cancer risk in an Eastern Chinese Han population.

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.

Polymorphisms in the kinesin-like factor 1 B gene and risk of epithelial ovarian cancer in Eastern Chinese women.

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.

XRCC1 polymorphisms and cervical cancer risk: an updated meta-analysis.

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.

T1-Weighted Imaging-Based Hippocampal Radiomics in the Diagnosis of Alzheimer's Disease.

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.

Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes.

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is an anti apoptotic and pro-oncogenic signaling molecule involved in the process of immunity, carcinogenesis and tumor progression. Single nucleotide polymorphisms (SNPs) at microRNA-binding sites may change messenger RNA target gene function, thus leading to cancer susceptibility and tumor progression. In this study of 1584 cervical cancer cases and 1394 cancer-free female controls, we investigated associations between three potentially functional SNPs in TNFAIP8 family genes and cervical cancer risk as well as platinum resistance and clinical outcomes in Eastern Chinese women. We found that the TNFAIP8-rs11064 variant GG genotype was associated with an increased risk of cervical cancer compared with AA/AG genotypes (adjusted odds ratio = 2.16, 95% confidence interval = 1.16-4.03, P = 0.015). Further in vitro and ex vivo functional experiments demonstrated that the TNFAIP8-rs11064 variant G allele weakened the binding affinity of miR-22 to the TNFAIP8 3'-untranslated region (UTR) in four cancer cell lines, resulting in increased production of the TNFAIP8 protein in the patients' cervical tissues. In the survival subset, the high TNFAIP8 protein expression was significantly associated with both resistance to cisplatin and nedaplatin, recurrence and death from cervical cancer. Taken together, in the absence of information on human papillomavirus (HPV) infection, the TNFAIP8-rs11064 SNP may function by affecting the affinity of miR-22 binding to the 3'-UTR of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk. Additionally, the increased TNFAIP8 protein expression may predict platinum resistance and clinical outcomes in cervical cancer patients. Larger, prospective studies with detailed HPV infection data are warranted to validate our findings.

Associations of Lys939Gln and Ala499Val polymorphisms of the XPC gene with cancer susceptibility: a meta-analysis.

XPC polymorphisms may alter DNA repair capacity, thus leading to genetic instability and carcinogenesis. Numerous studies have investigated the associations of XPC Lys939Gln (rs2228001) and Ala499Val (rs2228000) polymorphisms with cancer susceptibility; however, the findings are inconclusive. We searched literature from MEDLINE and EMBASE for eligible publications that assessed the associations between these two polymorphisms and cancer risk. We also assessed genotype-mRNA expression correlation data from HapMap for rs2228001 and rs2228000 in normal cell lines derived from 270 subjects with different ethnicities. The final analysis included 62 published studies of 25,708 cases and 30,432 controls for the Lys939Gln and 34 studies with 14,877 cases and 17,888 controls for the Ala499Val. Overall, Lys939Gln was significantly associated with an increased overall cancer risk (Gln/Gln vs. Lys/Lys: OR = 1.16, 95% CI = 1.07 - 1.25, p < 0.001; recessive model: OR = 1.14, 95% CI = 1.06 - 1.22, p < 0.001; dominant model: OR = 1.06, 95% CI = 1.01 - 1.11, p = 0.015 and Gln vs. Lys: OR = 1.07, 95% CI = 1.03 - 1.10, p < 0.001) and further stratifications showed an increased risk for bladder, lung and colorectal cancer, Asian populations and population-based studies. Likewise, Ala499Val was also significantly associated with an increased overall cancer risk (Val/Val vs. Ala/Ala: OR = 1.21, 95% CI = 1.07 - 1.36, p = 0.003 and recessive model: OR = 1.20, 95% CI = 1.08 - 1.34, p = 0.001) and further stratification showed an increased risk for breast and bladder cancer, particularly in Asian populations. Interestingly, significantly correlation between XPC genotypes and mRNA expression was found only for Asian populations as well. Despite some limitations, this meta-analysis established some solid statistical evidence for an association between XPC polymorphisms and cancer risk, which warrants further validation in single large studies.

Polymorphisms of the Interleukin 6 gene contribute to cervical cancer susceptibility in Eastern Chinese women.

Interleukin 6 (IL6) encodes a cytokine protein, which functions in inflammation, maintains immune homeostasis and plays important roles in cervical carcinogenesis. Single nucleotide polymorphisms (SNPs) in IL6 that cause variations in host immune response may contribute to cervical cancer risk. In this two-stage case-control study with a total of 1,584 cervical cancer cases and 1,768 cancer-free female controls, we investigated associations between two IL6 SNPs and cervical cancer risk in Eastern Chinese women. In both Study 1 and Study 2, we found a significant association of the IL6-rs2069837 SNP with an increased risk of cervical cancer as well as in their combined data (OR 1.27 and 1.19, 95% CI 1.08-1.49 and 1.04-1.36, P = 0.004 and 0.014 for dominant and additive genetic models, respectively). Furthermore, rs2069837 variant AG/GG carriers showed significantly higher levels of IL6 protein than did rs2069837 AA carriers in the target tissues. Using multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses, we observed some evidence of interactions of the IL6 rs2069837 SNP with age at primiparity and menopausal status in cervical cancer risk. We concluded that the IL6-rs2069837 SNP may be a marker for susceptibility to cervical cancer in Eastern Chinese women by a possible mechanism of altering the IL6 protein expression. Although lacked information on human papillomavirus (HPV) infection, our study also suggested possible interactions between IL6 genotypes and age at primiparity or menopausal status in cervical carcinogenesis. However, larger, independent studies with detailed HPV infection data are warranted to validate our findings.

Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population.

Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false-positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00-1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67-5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03-1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04-1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever-smokers, non-gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two-factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations.

A pri-miR-218 variant and risk of cervical carcinoma in Chinese women.

BACKGROUND: MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. METHODS: In this case-control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. RESULTS: We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. CONCLUSIONS: The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.

The association between common genetic variant of microRNA-146a and cancer susceptibility.

Published data on the association between microRNA-146a (miR-146a) G/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 23 studies including 10,585 cases and 12,183 controls were used in the meta-analysis. Overall, no significant associations were found between miR-146a G/C polymorphism and cancer risk when all studies pooled into the meta-analysis (GC vs. CC: OR=1.08, 95% CI=0.94-1.24; GG vs. CC: OR=1.13, 95% CI=0.93-1.37; dominant model: OR=1.09, 95% CI=0.94-1.26). In the subgroup analysis by ethnicity, still no significant associations were found. In the subgroup analysis by cancer type, statistically significantly increased risks were found for papillary thyroid carcinoma (GC vs. CC: OR=3.44, 95% CI=1.86-6.34; GG vs. CC: OR=2.20, 95% CI=1.22-3.99; dominant model: OR=2.68, 95% CI=1.48-4.83). In the subgroup analysis by population-based controls or hospital-based controls, no statistically significantly increased risks were found. Despite some limitations, this meta-analysis suggests that the miR-146a G allele is a low-penetrant risk factor for papillary thyroid carcinoma development.

[Impact of cigarette smoking on human sperm DNA integrity].

OBJECTIVE: To investigate the influence of cigarette smoking on human sperm DNA integrity. METHODS: Totally, 784 cases of male infertility were selected from our case database and grouped according to whether they were smokers or nonsmokers, how much they smoked (< or = 10, 11-19 and > or = 20 cigarettes/d) and how long they smoked (< or = 5, 6-9 and > or = 10 yr). Sperm DNA integrity was measured using sperm chromatin structure assay (SCSA) and flow cytometry. DNA fragmentation and immature spermatozoa were expressed by the DNA fragmentation index (DFI) and high DNA stainability (HDS) respectively. Conventional sperm parameters and sperm DNA integrity were compared among different groups. RESULTS: The total semen volume and percentage of grade a + b sperm were lower and the sperm morphological abnormality was higher in the > or = 20 cigarettes/d and > or = 10 yr groups than in the others (P < 0.05). DFI and HDS were significantly higher in the smokers than in the nonsmokers (P < 0.05). HDS was negatively correlated with the percentage of grade a + b sperm (r = -0.18, P < 0.05) and both DFI and HDS were positively correlated with the rate of sperm malformation (r = 0.31 and r = 0.39, P < 0.05). CONCLUSION: Smoking more than 20 cigarettes a day or longer than 10 years has deleterious effects on the semen volume, percentage of grade a + b sperm and sperm morphology of the smokers. Cigarette smoking decreases sperm DNA integrity and nuclear maturation.

Gynecological Cancers Translational, Research Implementation, and Harmonization: Gynecologic Cancer InterGroup Consensus and Still Open Questions.

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.

Surgical and oncological outcomes of an improved nerve-sparing radical hysterectomy technique: 6 years of experience at two centres.

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 50 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 50 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.

XPG gene rs751402 C>T polymorphism and cancer risk: Evidence from 22 publications.

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.

No association between TP53 Arg72Pro polymorphism and ovarian cancer risk: evidence from 10113 subjects.

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.

Wip1 suppresses ovarian cancer metastasis through the ATM/AKT/Snail mediated signaling.

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.

[Establishment of Immortal Lymphoblastoid Cell Lines of Non-syndromic Deafness Family and Several Methods fro Transforming Human B Lyphocyte by EB virus.].

Reservation of rare family materials is the base for us to do further research. Family of Jiang-Su Huai-Yin is one of the biggest non-syndromic deafness families in the world. In this family,deafness is maternally inherited and all the sufferers have the mitochondrial DNA 12s RNA A1555G mutation. Four methods are used in the experiments for establishing immortal lymphoblastoid cell lines of the family with non-syndromic deafness. Results were as follows: 1 cell line was from small amout of whole blood method, 1 cell line from frozen whole blood method, 14 cell lines from frozen leukocyte method, and 36 cell lines from cyclosporin A method. In this paper, we will discuss these four methods through our experiments of establishing cell lines.

CASP7 variants modify susceptibility to cervical cancer in Chinese women.

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.

Sequence analysis and phylogeny of deer (Cervidae) MtDNA control regions.

The complete control regions of three Muntiacinae species of Cervidae (M. reevesi, M. muntjak and M. crinifrons) were located after their complete mtDNA genomes were sequenced. In addition the control region sequences of nine species of other three Cervidae subfamilies were obtained from the Genbank. Base compositions, genetic distances and percent similarities among these regions were calculated and the homologous sequences were compared. Based on their control region sequences, the molecular phylogenetic tree was constructed by Neighbor-Joining method and rooted using the mtDNA control region sequence of O. aries. Furthermore, the phylogenetic relationship among the twelve species was discussed. The lengths of their control regions ranged from 909 bp to 1 049 bp and A + T content is 62.06%. The sequence alignment revealed considerable variation in 363 nucleotide sites (about 34%). According to the phylogenetic tree, we suggest: (1) As a whole, the phylogenetic taxon of the twelve Cervidae species based on their control region sequences is consistent with that made by the NCBI; (2) A. alces, a species of Alces (subfamily: Odocoileinae) is most antique one among the twelve Cervidae species; (3) M. reevesi is more antique than M. muntjak and M. crinifrons; (4) H. inermis, belonging to the subfamily Hydropotinae, is merged into the branch which includes C. capreolus and C. pygargus, two species of Capreolus (subfamily: Odocoileinae).