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1.
Mol Neurobiol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478144

RESUMO

Previous studies have suggested that certain variants in immune-related genes may participate in the pathogenesis of multiple sclerosis (MS), including rs17824933 in the CD6 gene, rs1883832 in the CD40 gene, rs2300747 in the CD58 gene, rs763361 in the CD226 gene, rs16944 in the IL-1ß gene, rs2243250 in the IL-4 gene, and rs12722489 and rs2104286 in the IL-2Rα gene. However, the results remained inconclusive and conflicting. In view of this, a comprehensive meta-analysis including all eligible studies was conducted to investigate the association between these 8 selected genetic variants and MS risk. Up to June 2023, 64 related studies were finally included in this meta-analysis. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) calculated by the random-effects model were used to evaluate the strength of association. Publication bias test, sensitivity analyses, and trial sequential analysis (TSA) were conducted to examine the reliability of statistical results. Our results indicated that rs17824933 in the CD6 gene, rs1883832 in the CD40 gene, rs2300747 in the CD58 gene, rs763361 in the CD226 gene, and rs12722489 and rs2104286 in the IL-2Rα gene may serve as the susceptible factors for MS pathogenesis, while rs16944 in the IL-1ß gene and rs2243250 in the IL-4 gene may not be associated with MS risk. However, the present findings need to be confirmed and reinforced in future studies.

2.
Endocrine ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38358556

RESUMO

PURPOSE: Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. To elucidate the molecular genetic basis of CPP, we here investigated the effects of polymorphism rs5780218, rs12998 and rs10158616 in KISS1 gene on CPP susceptibility. METHODS: The three KISS1 gene polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing in 422 healthy Hubei Chinese girls and 384 Hubei Chinese girls with CPP. RESULTS: Single-locus analysis demonstrated that rs5780218 and rs12998 were significantly associated with CPP susceptibility in Hubei Chinese girls. Haplotype analysis exhibited that the AGG carrying the risk allele A of rs5780218 and the -GG carrying the protective allele - of rs5780218 were associated with increased and decreased CPP susceptibility in Hubei Chinese girls, respectively. The following meta-analysis confirmed the contribution of rs5780218 and rs12998 on CPP susceptibility in Chinese girls. CONCLUSIONS: rs5780218 and rs12998 in the KISS1 gene may participate in genetic susceptibility to CPP in Chinese girls, and the KISS1 gene rs5780218 may serve as a genetic biomarker of CPP. However, the present findings should be validated in future studies with larger sample sizes in other ethnic populations.

3.
J Bioinform Comput Biol ; 21(4): 2350020, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37694487

RESUMO

Cancer is characterized by the dysregulation of alternative splicing (AS). However, the comprehensive regulatory mechanisms of AS in lung adenocarcinoma (LUAD) are poorly understood. Here, we displayed the AS landscape in LUAD based on the integrated analyses of LUAD's multi-omics data. We identified 13,995 AS events in 6309 genes as differentially expressed alternative splicing events (DEASEs) mainly covering protein-coding genes. These DEASEs were strongly linked to "cancer hallmarks", such as apoptosis, DNA repair, cell cycle, cell proliferation, angiogenesis, immune response, generation of precursor metabolites and energy, p53 signaling pathway and PI3K-AKT signaling pathway. We further built a regulatory network connecting splicing factors (SFs) and DEASEs. In addition, RNA-binding protein (RBP) mutations that can affect DEASEs were investigated to find some potential cancer drivers. Further association analysis demonstrated that DNA methylation levels were highly correlated with DEASEs. In summary, our results can bring new insight into understanding the mechanism of AS and provide novel biomarkers for personalized medicine of LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Processamento Alternativo , Multiômica , Fosfatidilinositol 3-Quinases , Adenocarcinoma de Pulmão/genética , Análise de Dados , Neoplasias Pulmonares/genética
4.
J Agric Food Chem ; 71(3): 1713-1726, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36634352

RESUMO

The widespread use of titanium dioxide nanoparticles (TiO2 NPs) in the food industry has brought about human safety risks related to nanotoxicity. In this study, food-related TiO2 NPs (anatase, 40 nm) were given to rats by oral gavage for 90 days at doses of 10, 100, and 1000 mg/kg bw. An additional two satellite groups underwent the same protocol for 45 days and for 90 days followed by a 28 day recovery. TiO2 NPs tended to agglomerate together in H2O, AGJ, and AIJ. No systemic toxicity was observed after 90 day agglomerated TiO2 NP exposure with no Ti distribution in major tissues/organs. Furthermore, TiO2 NP consumption for 90 days had no impact on microbiota diversity; the community structure of the gut microbiota is shifted to some extent at the genus level. Collectively, the NOAEL of agglomerated TiO2 NPs for 90 days of oral administration was 1000 mg/kg bw, the highest dose tested in male and female rats.


Assuntos
Microbioma Gastrointestinal , Nanopartículas Metálicas , Nanopartículas , Humanos , Ratos , Masculino , Feminino , Animais , Titânio/toxicidade , Titânio/química , Distribuição Tecidual , Nanopartículas/toxicidade , Administração Oral , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química
5.
Artigo em Inglês | MEDLINE | ID: mdl-36533675

RESUMO

Recently, the rs41291957 polymorphism in the promoter region of miR-143/145 has been repeatedly investigated for its contribution to cancer susceptibility. However, the results remain conflicting rather than conclusive, which calls for further investigations. Therefore, we here conducted a case-control study and meta-analysis to explore the association between rs41291957 and cancer risk. In the case-control study, a total of 2277 cancer patients (lung, liver, gastric and colorectal cancers) and 800 normal controls were recruited, the genotyping of rs41291957 was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. In the meta-analysis, 5 previously published studies and our present study were included, the STATA 14.0 software was applied to conduct all statistical analyses. The results of case-control study showed that rs41291957 was significantly associated with the risk of gastric cancer, colon cancer, rectal cancer, and colorectal cancer in Hubei Han Chinese population. The results of meta-analysis demonstrated that rs41291957 was significantly associated with overall cancer risk, especially colorectal cancer risk and lung cancer risk. Collectively, the rs41291957 polymorphism of miR-143/145 may be a plausible susceptible locus for cancer risk, which should be validated in future studies with larger samples in different ethnic populations.


Assuntos
Neoplasias do Colo , MicroRNAs , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , MicroRNAs/genética , Genótipo
6.
Pathol Res Pract ; 240: 154212, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36410173

RESUMO

Previous studies have repeatedly investigated the effects of MALAT1 gene rs3200401 and MEG3 gene rs7158663 on cancer risk. However, their results remain conflicting rather than conclusive. Therefore, we here performed a case-control study and a followed meta-analysis to examine their contribution to the risk of lung, colorectal, gastric and liver cancer. 550 lung cancer patients, 787 colorectal cancer patients, 460 gastric cancer patients, 480 liver cancer patients and 800 normal controls were included. The genotyping of rs3200401 and rs7158663 was applied with Sanger sequencing technology. Our case-control study revealed that in Hubei Chinese population, rs3200401 was significantly associated with the risk of gastric cancer but not lung, colorectal, or liver cancer, rs7158663 was significantly associated with the risk of gastric and colorectal cancer but not lung or liver cancer. The followed meta-analysis, combining the data of previous studies and present study, showed that rs3200401 was significantly associated with the risk of gastric and colorectal cancer in the pooled population but not liver cancer in Chinese population, rs7158663 was significantly associated with the risk of lung, colorectal and gastric but not liver cancer in Chinese population. Collectively, MALAT1 gene rs3200401 may be a susceptive factor for the development of colorectal and gastric cancer, and MEG3 gene rs7158663 may be a susceptive factor for the development of lung, colorectal and gastric cancer. However, the findings should be validated in future studies with larger sample sizes of different ethnic populations.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Estudos de Casos e Controles , Neoplasias Hepáticas/genética , Neoplasias Colorretais/genética
7.
Pathol Res Pract ; 229: 153696, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34839094

RESUMO

BACKGROUND: mTOR, mLST8 and RAPTOR are the core components of mTORC1, which has been found to be closely related to tumorigenesis. Currently, multiple single nucleotide polymorphisms (SNPs) in mTOR gene (rs2295080, rs17036508 and rs1034528), mLST8 gene (rs3160 and rs26865) and RPTOR gene (rs1062935, rs3751932, rs3751834, rs12602885) have been extensively studied for their associations with cancer risk. However, the results remained inconclusive and conflicting. Therefore, we here performed a meta-analysis of all available studies to investigate the association between these SNPs and cancer risk. METHODS: Up to April 2021, 25 related publications were retrieved and included in this meta-analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) calculated by fixed or random effects models were applied to assess the strength of association. Trial Sequential Analysis (TSA) was conducted to weaken the random error and enhance the reliability of evidence. RESULTS: After Bonferroni correction, it was revealed that rs3160, rs26865, rs1062935, rs3751932, rs3751834 and rs10602885 were not associated with cancer risk. However, rs17036508 and rs1034528 showed significant association with total cancer risk. A significant association was also found between rs2295080 and total cancer risk, and stratified analysis by cancer type suggested that rs2295080 was specifically associated with acute lymphoblastic leukemia risk, prostate cancer risk, and breast cancer risk. CONCLUSIONS: The present meta-analysis suggested that the rs2295080, rs17036508 and rs1034528 polymorphisms in mTOR gene may be the susceptive factors for cancer development, while the target genetic polymorphisms in mLST8 gene or RPTOR gene may not be associated with cancer risk. However, these findings remain to be confirmed or further reinforced in large and well-designed studies in different ethnic populations.


Assuntos
Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Serina-Treonina Quinases TOR/genética , Humanos , Neoplasias/epidemiologia , Medição de Risco
8.
Pathol Res Pract ; 228: 153690, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34808559

RESUMO

To examine the role of IL-22 gene in colorectal cancer (CRC) susceptibility, we identified causative genetic polymorphisms in promoter region of IL-22 gene and explored the mechanism underlying their contribution to CRC development in a Chinese population of Hubei province. 13 target single nucleotide polymorphisms (SNPs) in IL-22 gene promoter were genotyped in 787 CRC patients (426 colon cancer and 361 rectal cancer) and 800 normal controls. The results demonstrated that the rs2227478 T > C polymorphism was significantly associated with the risk of colon cancer, rectal cancer and CRC, and the C allele was associated with a decreased cancer risk than the T allele. In CRC tissue samples, the subjects with CT+CC genotypes of rs2227478 had lower levels of IL-22 mRNA than the subjects with TT genotypes. Further functional analysis revealed that the transcription repressor Sp1 possessed a higher binding affinity to the C allele than the T allele. Collectively, the rs2227478 T > C is a functional genetic polymorphism that significantly reduces the CRC risk in a Han Chinese population.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença/genética , Interleucinas/genética , Adulto , Idoso , Povo Asiático/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Interleucina 22
9.
J Assist Reprod Genet ; 38(10): 2781-2789, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34403018

RESUMO

PURPOSE: Polycystic ovary syndrome (PCOS) is a highly complex disorder influenced by genetic and environmental factors. Previous association studies have identified multiple PCOS-susceptible loci, but there is no consistent conclusion, which calls for further investigations. METHODS: In the present case-control study, FSHR gene variants (rs2268361, rs6165, and rs6166), LHCGR gene variant (rs13405728), THADA gene variant (rs13429458), DENND1A gene variants (rs10818854 and rs2479106), and INSR gene variants (rs2059807 and rs1799817) were genotyped with Sanger sequencing in a total of 400 PCOS women and 480 healthy women. RESULTS: After Bonferroni correction, our results showed that rs13405728, rs13429458, rs2479106, rs10818854, and rs2059807 were significantly associated with PCOS risk in Chinese women. To improve the statistical strength, a further meta-analysis in Asian population was conducted. Although rs6166 and rs1799817 were not associated with PCOS risk in the present study, they were identified to be strongly associated with PCOS risk in the pooled Koreans and Chinese respectively. No significant association with PCOS risk was consistently found for rs2268361 or rs6165. Moreover, the pooled results further confirmed the significant association with PCOS risk for rs13405728, rs13429458, rs2479106, rs10818854, and rs2059807. CONCLUSIONS: Collectively, the rs6166, rs13405728, rs13429458, rs2479106, rs10818854, rs2059807, and rs1799817 may indeed be the genetic risk factors for PCOS in Asian population, which requires further investigation using larger independent sets of samples in different ethnic populations.


Assuntos
Povo Asiático/genética , Marcadores Genéticos , Predisposição Genética para Doença , Síndrome do Ovário Policístico/epidemiologia , Polimorfismo de Nucleotídeo Único , Adulto , Ásia/epidemiologia , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla , Humanos , Síndrome do Ovário Policístico/genética
10.
Pathol Res Pract ; 216(12): 153237, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33065483

RESUMO

Recently, four single nucleotide polymorphisms (rs2585428, rs4809960, rs6022999 and rs6068816) in CYP24A1 gene were extensively studied for their associations with cancer risk. However, these studies included only a few types of cancer, which calls for further investigations. In view of this, we here conducted a case-control study to explore the associations between these four CYP24A1 gene polymorphisms and risk of liver, lung and gastric cancer in a Chinese population. A total of 480 liver cancer patients, 550 lung cancer patients, 460 gastric cancer patients and 800 normal controls were recruited in this study. The genotyping of CYP24A1 gene polymorphisms was applied with Sanger sequencing assay. Single-locus analysis demonstrated that rs6022999 was significantly associated with risk of liver and lung cancer, while rs6068816 was significantly associated with the risk of gastric cancer. Haplotype analysis revealed that haplotype GTAT was associated with an increased risk of liver cancer and a decreased risk of lung cancer, and haplotype ATGC was associated with a decreased risk of lung cancer. The further meta-analysis of rs6068816 and lung cancer risk showed that rs6068816 was not associated with lung cancer risk in Chinese population, which confirmed our present finding. Conclusively, rs6022999 may be a genetic biomarker for liver and lung cancer susceptibility in Chinese population, and rs6068816 may be used to predict gastric cancer risk in Chinese population.


Assuntos
Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Neoplasias Gástricas/genética , Vitamina D3 24-Hidroxilase/genética , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etnologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etnologia
11.
Int J Clin Oncol ; 25(4): 521-530, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31832882

RESUMO

BACKGROUND: Interleukin-22 (IL22) has been implicated in inflammation and tumorigenesis. The association between IL22 gene polymorphisms and cancer risk has been widely explored. However, the limited sample sizes of previous studies may produce inadequate statistical power and conflicting results, which calls for further investigations. In this study, we recruited a total of 1490 cancer patients (480 liver cancer patients, 550 lung cancer patients, and 460 gastric cancer patients) and 800 normal controls to explore the associations between IL22 gene polymorphisms (rs1179251, rs2227485, rs2227511, and rs2227473) and cancer risk. METHOD: The genotyping was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. RESULTS: Our results showed that none of the four IL22 gene polymorphisms was associated with the risk of liver, lung or gastric cancer in Hubei Han Chinese population. To improve the statistical strength, a meta-analysis was further conducted. The results further confirmed our present findings and showed that rs1179251, rs2227485, and rs2227473 were not associated with cancer risk in total or stratified analysis. CONCLUSION: Consequently, the rs1179251, rs2227485, rs2227511, and rs2227473 polymorphisms may not be associated with cancer risk. However, further investigations using larger samples in different ethnic populations are required.


Assuntos
Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/genética , Interleucina 22
12.
Pathol Res Pract ; 216(1): 152735, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31740231

RESUMO

CYP24A1, an essential gene in regulation of vitamin D, has been reported to play an important role in enhancing immune activity and inhibiting tumorigenesis. Previous studies proposed that rs2585428, rs4809960, rs6022999 and rs6068816 in CYP24A1 gene might be greatly associated with cancer risk. To validate the findings, we here investigated the associations of these four polymorphisms and colorectal cancer (CRC) risk in a central Chinese population (426 colon cancer patients, 361 rectal cancer patients and 800 healthy controls). The genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Our results revealed that the rs4809960 and rs6022999 were strongly associated with the CRC risk, especially with the colon cancer risk. Moreover, the analysis of haplotypes consisting of rs2585428(G > A), rs4809960(T > C), rs6022999(A > G) and rs6068816(C > T) indicated that haplotype ATGC significantly decreased the CRC risk, especially the colon cancer risk. Haplotype GCAT significantly increased the CRC risk, especially the rectal cancer risk. However, haplotype ACAC was only found to be associated with increased risk of CRC. To improve the statistical strength, an updated meta-analysis was further performed. The results showed that rs2585428 was associated with cancer risk in Caucasian population, rs4809960 was associated with breast cancer risk in Caucasian population, and rs6022999 was associated with cancer risk in Asian population. Collectively, the rs4809960 and rs6022999 may be the genetic biomarkers for prediction of colon cancer risk in Chinese population, the rs2585428 and rs6022999 may link to cancer susceptibility in Caucasian population and in Asian population respectly.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença/genética , Polimorfismo de Fragmento de Restrição/genética , Vitamina D3 24-Hidroxilase/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Vitamina D3 24-Hidroxilase/metabolismo
13.
Pathol Res Pract ; 215(5): 1061-1065, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30846411

RESUMO

The rs3787016 polymorphism, in polymerase II polypeptide E (POLR2E), was previously identified as being associated with the risk for prostate cancer, esophageal cancer, breast cancer, papillary thyroid carcinoma and liver cancer, suggesting that rs3787016 may server as a common genetic factor to affect individual susceptibility to cancer. To prove the hypothesis, we here performed a case-control study to explore the association between rs3787016 and cervical cancer risk, and to confirm the association between rs3787016 and breast cancer in a central Chinese population, which was followed by a meta-analysis to precisely estimate the association between rs3787016 and risk of female breast and cervical cancer. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Our results indicated that rs3787016 was associated with the risk of both breast cancer and cervical cancer, and stratified analysis indicated that the association remained particularly for ≤60 years old females who smoke and drink. Moreover, after grouping breast cancer and cervical cancer together, our meta-analysis demonstrated that rs3787016 was associated with overall cancer risk and breast cancer risk. Collectively, the POLR2E rs3787016 polymorphism may be a valuable biomarker for female breast and cervical cancer predisposition.


Assuntos
Neoplasias da Mama/genética , RNA Polimerases Dirigidas por DNA/genética , Predisposição Genética para Doença/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
14.
J Cell Biochem ; 120(8): 12949-12957, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30860617

RESUMO

The rs187115, an intronic variant of CD44 gene, has been previously reported to play a potential role in genetic susceptibility to cancer. Here, we comprehensively examined the association between CD44 rs187115 variant and cancer risk (breast cancer, cervical cancer, lung cancer, gastric cancer, liver cancer, colon cancer, and rectal cancer) in a central Chinese population. The rs187115 variant was genotyped with the polymerase chain reaction-restriction fragment length polymorphism assay. In this study, we observed that rs187115 was associated with the risk of cervical, lung, and liver cancer, but not with the risk of breast, gastric, colon, rectal or colorectal cancer. Of note, the G allele and G allele genotypes of rs187115 conferred an increased risk of cervical, lung, and liver cancer. To improve the statistical strength, a followed meta-analysis was conducted. The results demonstrated that rs187115 was significantly associated with cancer risk, and the significant association remained in the stratification analysis by ethnicity, genotyping method, and cancer type. Collectively, the CD44 rs187115 variant may be associated with the risk of cervical, lung, and liver cancer in the central Chinese population, and may be used as a potential biomarker for cancer predisposition in the Asian population, especially in the Chinese population.


Assuntos
Predisposição Genética para Doença/genética , Receptores de Hialuronatos/genética , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/genética , Alelos , Povo Asiático/genética , China , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Neoplasias Hepáticas/etnologia , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias do Colo do Útero/etnologia
15.
Biosci Rep ; 38(6)2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30291213

RESUMO

How single nucleotide polymorphisms in long non-coding RNAs are involved in cancer susceptibility remains poorly understood. We hypothesized that polymerase II polypeptide E (POLR2E) rs3787016 polymorphism, identified in a genome-wide association study of prostate cancer, might be a common genetic risk factor for cancer risk. To address this issue, we here conducted a case-control study to investigate the association of POLR2E rs3787016 polymorphism with risk of liver and lung cancer (including 800 normal controls, 480 liver cancer patients, and 550 lung cancer patients), followed by a meta-analysis. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. Although no significant association was found for rs3787016 with risk of liver or lung cancer, the further stratified analysis identified that rs3787016 contributed to liver cancer risk particularly for over than 60 years individuals who drink. Moreover, the meta-analysis demonstrated that rs3787016 was associated with overall cancer risk and prostate cancer risk. Collectively, the POLR2E rs3787016 polymorphism may be a valuable biomarker for cancer predisposition.


Assuntos
Biomarcadores Tumorais/genética , RNA Polimerases Dirigidas por DNA/genética , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Fígado , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
16.
Technol Cancer Res Treat ; 17: 1533033818801550, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30244662

RESUMO

The rs937283 variant, locating in murine double minute 2 promoter region, has been previously reported to potentially alter the promoter activity and to influence cancer susceptibility. In this study, we investigated the association of murine double minute 2 rs937283 variant and cancer susceptibility in a central Chinese population, followed by a meta-analysis. A total of 1058 healthy controls, 480 patients with breast cancer, 384 patients with cervical cancer, 480 patients with liver cancer, 426 patients with colon cancer, and 361 patients with rectal cancer were recruited in this case-control study. The murine double minute 2 rs937283 was genotyped by polymerase chain reaction restriction fragment length polymorphism and confirmed by sequencing. Our case-control analysis revealed that rs937283 was associated with the susceptibility to breast and liver cancer, but not cervical, colon, or rectal cancer. Specifically, the G allele of rs937283 conferred a significantly increased risk of breast and liver cancer. Moreover, results of meta-analysis demonstrated that rs937283 was significantly associated with cancer susceptibility, and this significant association remained in Asian (Chinese) population, but not in Caucasian population. Collectively, the murine double minute 2 rs937283 variant may serve as a potential biomarker for cancer predisposition in Chinese population.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Proteínas Proto-Oncogênicas c-mdm2/genética , Adulto , Idoso , Povo Asiático/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Genótipo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , População Branca/genética
17.
Biosci Rep ; 38(5)2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30054425

RESUMO

Lung cancer is a malignant tumor with high fatality rate and causes great harm to human economic life. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. With the rapid development of epigenetic study in the last decade, the understanding of the pathogenesis of lung cancer and the development of personalized treatment of lung cancer are picking up pace. Previous studies showed that miR-29 family members (miR-29s; miR-29a, -29b, and -29c) are down-regulated in most human cancers, including NSCLC, but their biological roles in tumorigenesis and their regulation mechanism are still not fully elucidated. Herein, we reported that the miR-29a, -29b and, -29c were coincidently down-regulated in NSCLC, and the histone H3K9 methyltransferase SET domain, bifurcated 1 (SETDB1) was directly targetted by miR-29s Moreover, SETDB1 negatively regulated the expression of TP53 and overexpression of SETDB1 down-regulating the expression of miR-29s, while TP53 positively regulated the expression of miR-29s and overexpression of TP53 down-regulated the expression of SETDB1. On the other side, as a downstream target of TP53, the H3K9 methyltransferase Suv39h1 was also down-regulated by miR-29s via up-regulating TP53 expression. The further detection of H3K9 methylation status after changes in miR-29s expression revealed that they negatively regulated the levels of H3K9 di- and trimethylation in NSCLC. Collectively, our findings highlight a TP53/miR-29s/SETDB1 regulatory circuitry and assign a role of H3K9 methylation regulator to miR-29s, which may be a potential therapeutic target in the treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Metiltransferases/genética , Proteína Supressora de Tumor p53/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Histona-Lisina N-Metiltransferase , Histonas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Família Multigênica , Proteínas Metiltransferases/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor p53/metabolismo
18.
Int J Clin Oncol ; 23(5): 867-876, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29777315

RESUMO

BACKGROUND: Currently, the MDM2 promoter rs937283 A > G variant that is able to alter MDM2 gene expression has been widely studied to explore the association of MDM2 with cancer risk. In this report, we investigate the association of MDM2 rs937283 A > G variant with risk of lung cancer (LC) and gastric cancer (GC) in a Chinese population of Hubei province, which was followed by a meta-analysis. METHODS: The genotyping of rs937283 was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. RESULTS: The results of the present study showed that rs937283 was significantly associated with the risk of LC, and the factors of age, gender, smoking status and drinking status would affect such association. However, rs937283 was only associated with the risk of GC in male, smoking and drinking subgroups. The following meta-analysis demonstrated that rs937283 was associated with the overall cancer risk particularly in Chinese population, which reinforced our present finding. Moreover, the meta-analysis according to cancer types revealed that rs937283 was associated with retinoblastoma risk, but not squamous cell carcinoma risk. CONCLUSION: Collectively, the MDM2 rs937283 A > G variant may be a valuable risk factor or diagnostic biomarker for Chinese cancer patients.


Assuntos
Povo Asiático/genética , Biomarcadores Tumorais/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2/genética , Neoplasias Gástricas/genética , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Retinoblastoma/epidemiologia , Retinoblastoma/genética , Retinoblastoma/patologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia
19.
Pathol Res Pract ; 214(7): 1040-1044, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29724531

RESUMO

Long non-coding RNAs (LncRNAs) have been shown to be involved in cancer tumorigenesis and progression. Single nucleotide polymorphisms (SNPs) in the lncRNAs also play a vital role in carcinogenesis. We here explored the association between POLR2E rs3787016 and risk of papillary thyroid carcinoma (PTC) in a Chinese population, which was followed by a meta-analysis of POLR2E rs3787016 and cancer risk in Chinese population. A total of 409 PTC patients and 800 healthy individuals were enrolled in the present study. The POLR2E rs3787016 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and was confirmed by sequencing. The POLR2E rs3787016T allele increased the PTC risk in Chinese population, particular in Chinese females. The meta-analysis further revealed that POLR2E rs3787016T allele was associated with an increased cancer risk in Chinese population. Collectively, the POLR2E rs3787016 may be used as a genetic biomarker to predict cancer risk in Chinese population.


Assuntos
Carcinoma Papilar/genética , Carcinoma/patologia , RNA Polimerases Dirigidas por DNA/genética , Predisposição Genética para Doença/genética , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Carcinoma/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Risco , Câncer Papilífero da Tireoide
20.
Int J Biol Markers ; 33(2): 195-200, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29027179

RESUMO

PURPOSE: To investigate the association of DNMT3B -283T>C polymorphism with the risk of lung or gastric cancer, which was followed by a meta-analysis. METHODS: The genotyping of -283T>C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and was confirmed by sequencing. RESULTS: The results of this case-control study showed that -283T>C was not associated with the risk of lung or gastric cancer, and further stratified analysis according to age, gender, smoking status, and alcohol status confirmed the present finding. However, data from a meta-analysis in the Asian population revealed a significant association between -283T>C and lung cancer risk in the allelic model (C vs. T: odds ratio [OR] = 1.28, 95% confidence interval [CI], 1.06-1.55, p = 0.01) and two genetic models (CC vs. TC: OR = 1.29, 95% CI, 1.04-1.59, p = 0.02; CC vs. TC + TT: OR = 1.30, 95% CI, 1.06-1.60, p = 0.01). CONCLUSIONS: These results provided evidence that the DNMT3B -283T>C polymorphism might significantly contribute to the lung cancer risk in the Asian population, but not the gastric cancer risk in the Chinese population.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Neoplasias Gástricas/genética , Alelos , China/epidemiologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , DNA Metiltransferase 3B
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