Trends in the incidence and survival of cancer in individuals aged 55 years and older in the United States, 1975-2019.

BACKGROUND: In ageing societies such as the United States, evaluating the incidence and survival rates of cancer in older adults is essential. This study aimed to analyse the incidence and survival rates of cancer in individuals aged 55 years or older in the United States. METHODS: This retrospective study (1975-2019) was conducted using combined registry data from the Surveillance, Epidemiology, and End Results database. Data from the 9, 12, and 17 Registries (Nov 2021 Sub) datasets were used. RESULTS: In 2019, the incidence of cancer in individuals older than 55 years and the overall population was 1322.8 and 382.1 per 100,000 population, respectively. From 2000 to 2019, the incidence of cancer in individuals older than 55 years showed a decreasing trend, whereas their five-year survival rates showed an increasing trend. The incidence of cancer in the 75-79 and 80-84 year age groups was the highest among all age groups. CONCLUSIONS: The incidence of colon cancer declined significantly, whereas that of intrahepatic bile duct cancer increased considerably. These trends may be due to increased screening for cancers with high incidence rates and improved control of the risk factors for cancer. Rapid development of targeted therapy and immunotherapy combined with early tumour detection may be an important reason for the improved survival rates.

Trends in death and life lost due to bladder cancer in Suzhou Cityfrom 2003 to 2022 / 预防医学

Objective @#To analyze the trends in mortality and life lost due to bladder cancer in Suzhou City, Jiangsu Province from 2003 to 2022, so as to provide the reference for prevention and treatment strategy of bladder cancer.@*Methods@# The data of bladder cancer death in Suzhou City from 2003 to 2022 were collected through Suzhou Residents' Death Registration System, including age, gender, date of death and underlying cause of death. The crude mortality, standardized mortality, years of potential life lost (PYLL), standardized years of potential life lost (SPYLL), years of potential life lost rate (PYLLR), standardized years of potential life lost rate (SPYLLR) and average years of life lost (AYLL) were calculated. The average annual percent change (AAPC) was used to analyze the trends in bladder cancer death and life lost. @*Results@#Totally 2 978 deaths occurred due to bladder cancer in Suzhou City from 2003 to 2022. The crude mortality was 2.22/105, which appeared a tendency towards a rise (AAPC=4.271%, P<0.05). The standardized mortality was 0.91/105, which appeared no significant changing trend (P>0.05). The standardized mortality was 1.58/105 in males and 0.37/105 in females, which appeared no significant tendency in males (P>0.05) and appeared a tendency towards a decline in females (AAPC=-2.331%, P<0.05). The age-specific crude mortality was low among people who aged under 45 years, began to rise among people aged over 45 years and peaked among people aged 60 years and older. The crude mortality of bladder cancer in males aged 60 years and older showed an increasing trend (AAPC=2.864%, P<0.05), but there was no significant tendency in females aged 60 years and older (P>0.05). The PYLL, SPYLL, PYLLR, SPYLLR and AYLL of bladder cancer were 5 020.00 person-years, 2 945.14 person-years, 0.04‰, 0.03‰ and 9.07 years per person. SPYLL, SPYLLR and AYLL showed an decreasing trend (AAPC=-2.867%, -3.321%, -3.738%, P<0.05). @*Conclusions@#The mortality of bladder cancer in Suzhou City appeared a tendency towards a rise from 2003 to 2022. The PYLL appeared a downward trend. Males aged 60 years and older are the key groups for the prevention and control of bladder cancer.

CgB promotes EMT and stemness via MAPK pathway in colonic neuroendocrine carcinoma.

The incidence of colorectal neuroendocrine tumors is increasing every year with poor prognosis. Members of Chromogranin family proteins have been shown to be associated with cancer metastasis; however, the role of chromogranin B in colonic neuroendocrine carcinoma (NEC) is unknown. In this study, we investigated the expression and function of CgB in colonic NEC. Using RNA-seq data from GSE 9576 and GSE 142720 datasets, we analyzed the differentially expressed genes between the normal and NEC samples, which protein levels were further validated using the Human Protein Atlas (HPA) databases. Moreover, immunohistochemistry staining and biological experiments were conducted to examine the expression and function of CgB in colonic NEC. Western blot was also performed to confirm the effect of CgB on epithelial mesenchymal transition (EMT) and its related pathways. We found that the expression level of CgB was significantly higher in colonic NEC tissues than in the adjacent tissues. The upregulation of CgB promoted cell invasion and migration as well as activated EMT and stemness. Mechanistically, both pathway enrichment analysis and Western blot analysis confirmed that CgB overexpression activated p38 MAPK and ERK pathways, while silencing CgB showed the opposite effects. Collectively, our results suggested that CgB activated p38 MAPK and ERK pathways, thereby contributing to the development of colonic NEC.

Death and life loss due to female breast cancer in Suzhou City from 2007 to 2021 / 预防医学

Objective@#To investigate the trends in mortality and life lost due to female breast cancer among in Suzhou City from 2007 to 2021, so as to provide insights into improvements of breast cancer control strategy in Suzhou City.@*Methods@#The epidemiological and clinical data pertaining to dead female breast cancer cases in Suzhou City from 2007 to 2021 were collected from Suzhou Municipal Chronic Disease Surveillance System, including gender, age and cause of death. The crude mortality, standardized mortality, years of potential life lost (YPLL), years of potential life lost rate (YPLLR), standardized YPLL (SYPLL), standardized YPLLR (SYPLLR) and average years of life lost (AYLL) due to female breast cancer were calculated. All data were standardized by the Fifth National Population Census in 2000, and the trends in mortality of breast cancer were estimated using average annual percent change (AAPC). @*Results@#Totally 4 425 death occurred due to female breast cancer in Suzhou City from 2007 to 2021, with a crude mortality rate of 8.67/105, which appeared a tendency towards a rise (AAPC=1.83%, t=5.080, P=0.001), and the standardized mortality was 4.68/105, which appeared no significant changes (AAPC=0.13%, t=0.356, P=0.727). The crude mortality rates of female breast cancer were 0.62/105, 10.33/105 and 21.69/105 among women at ages of 15 to 34, 35 to 64 years and 65 years and older, respectively, which appeared a tendency towards a rise (χ2trend=2 315.683, P=0.001). The crude mortality of female breast cancer was 8.66/105 in urban areas and 8.86/105 in rural areas, both appearing a tendency towards a rise (urban areas: AAPC=1.73%, t=3.290, P=0.006; rural areas: AAPC=2.68%, t=6.565, P=0.001). The YPLL, SYPLL, YPLLR, SYPLLR and AYLL of female breast cancer were 44 485 person-years, 30 387 person-years, 0.99‰, 0.68‰ and 14.94 years per person, and both YPLLR (AAPC=-1.06%, t=-2.193, P=0.047) and AYLL (AAPC=-1.53%, t=-4.783, P=0.001) appeared a tendency towards a reduction, respectively. @*Conclusion@#The crude mortality of female breast cancer appeared a tendency towards a rise and the life loss appeared a tendency towards a decline in Suzhou City from 2007 to 2021. The elderly population should be given a high priority for breast cancer control.

Development and validation of a prognostic 9-gene signature for colorectal cancer.

Introduction: Colorectal cancer (CRC) is one of the most prevalent cancers globally with a high mortality rate. Predicting prognosis using disease progression and cancer pathologic stage is insufficient, and a prognostic factor that can accurately evaluate patient prognosis needs to be developed. In this study, we aimed to infer a prognostic gene signature to identify a functional signature associated with the prognosis of CRC patients. Methods: First, we used univariate Cox regression, least absolute shrinkage and selection operator (lasso) regression, and multivariate Cox regression analyses to screen genes significantly associated with CRC patient prognosis, from colorectal cancer RNA sequencing data in The Cancer Genome Atlas (TCGA) database. We then calculated the risk score (RS) for each patient based on the expression of the nine candidate genes and developed a prognostic signature. Results: Based on the optimal cut-off on the receiver operating characteristic (ROC) curve, patients were separated into high- and low-risk groups, and the difference in overall survival between the two groups was examined. Patients in the low-risk group had a better overall survival rate than those in the high-risk group. The results were validated using the GSE72970, GSE39582, and GSE17536 Gene Expression Omnibus (GEO) datasets, and the same conclusions were reached. ROC curve test of the RS signature also indicated that it had excellent accuracy. The RS signature was then compared with traditional clinical factors as a prognostic indicator, and we discovered that the RS signature had superior predictive ability. Conclusion: The RS signature developed in this study has excellent predictive power for the prognosis of patients with CRC and broad applicability as a prognostic indicator for patients.

Tumor stem cell-derived exosomal microRNA-17-5p inhibits anti-tumor immunity in colorectal cancer via targeting SPOP and overexpressing PD-L1.

Exosomes are known to transmit microRNAs (miRNAs) to affect human cancer progression, and miR-17-5p has been manifested to exert facilitated effects on colorectal cancer (CRC) progression, while the role of tumor stem cells-derived exosomal miR-17-5p in CRC remains unknown. We aim to explore the effect of CRC stem cells-derived exosomes (CRCSC-exos) conveying miR-17-5p on CRC. The exosomes were isolated from CRC stem cells and identified. HCT116 cells were transfected with speckle-type POZ protein (SPOP) interfering vector or co-cultured with exosomes carrying miR-17-5p mimic/inhibitor. Then, the proliferation, migration, invasion, and apoptosis of the cells were determined. The xenograft mouse model was constructed using BALB/C mice and the serum levels of T cell cytokines were assessed. Expression of miR-17-5p, SPOP, CD4, CD8 and programmed death ligand 1 (PD-L1) was detected. The targeting relationship between miR-17-5p and SPOP was verified. MiR-17-5p was upregulated and SPOP was downregulated in CRC tissues. CRCSC-exos transmitted miR-17-5p to HCT116 cells to promote malignant behaviors and suppress anti-tumor immunity of HCT116 cells. The overexpressed SPOP exerted opposite effects. SPOP was confirmed as a target gene of miR-17-5p. Upregulated CRCSC-exosomal miR-17-5p inhibits SPOP to promote tumor cell growth and dampen anti-tumor immunity in CRC through promoting PD-L1.

Surface Acoustic Wave DMMP Gas Sensor with a Porous Graphene/PVDF Molecularly Imprinted Sensing Membrane.

In this paper, surface acoustic wave (SAW) sensors containing porous graphene/PVDF (polyvinylidene fluoride) molecularly imprinted sensitive membrane for DMMP gas detection were investigated. A 433 MHz ST-cut quartz SAW resonator was used to convert gas concentration changes into frequency shifts by the sensors. The porous graphene/PVDF film was fabricated on the sensor's surface by using the tape-casting method. DMMP molecules were adsorbed on the porous structure sensing film prepared by the 2-step method to achieve the specific recognition effect. The sensitivity of the sensor could reach -1.407 kHz·ppm-1. The response time and recovery time of the SAW sensor with porous graphene/PVDF sensing membrane were about 4.5 s and 5.8 s at the concentration of 10 ppm, respectively. The sensor has good anti-interference ability to most gases in the air.

Scutellarin resensitizes oxaliplatin-resistant colorectal cancer cells to oxaliplatin treatment through inhibition of PKM2.

Although oxaliplatin is an effective chemotherapeutic drug commonly used for colorectal cancer (CRC) treatment, drug resistance usually occurs during the long-term use of it. It is urgent to create strategies to reduce the resistance of CRC cells to oxaliplatin. Oxaliplatin-resistant CRC cells (OR-SW480 and OR-HT29) were acquired through long-term exposure of CRC cells to oxaliplatin. It was found that OR-SW480 and OR-HT29 cells exhibited obvious lower sensitivity and a higher metabolism rate of glucose compared to their parental SW480 and HT29 cells, respectively. However, combination with scutellarin significantly resensitized the OR-SW480 and OR-HT29 cells to oxaliplatin-induced cytotoxicity. Mechanically, overexpression of pyruvate kinase isoenzyme M2 (PKM2) was responsible for the resistance to oxaliplatin in OR-SW480 and OR-HT29. Combination with scutellarin was able to inhibit the PKM2 activity and thus reduced the production of adenosine triphosphate (ATP) to sensitize the oxaliplatin-induced mitochondrial apoptosis pathway in both OR-SW480 and OR-HT29 cells. It was indicated that scutellarin resensitizes oxaliplatin-resistant CRC cells to oxaliplatin treatment through inhibition of PKM2.

Down-regulation of lncRNA DNAJC3-AS1 inhibits colon cancer via regulating miR-214-3p/LIVIN axis.

Long non-coding RNAs (lncRNAs) play a key role in the development and metastasis of cancer. However, the biological role and clinical significance of lncRNA DNAJC3-AS1 in the development of colon cancer is still unknown. In this study, the effects of DNAJC3-AS1 on cell proliferation, migration, and invasion were evaluated by MTT assay, wound-healing assay, and transwell assay, respectively. The relationship between DNAJC3-AS1, miR-214-3p and LIVIN was predicted by the online software and confirmed by dual-luciferase reporter assay. We found that the down-regulation of DNAJC3-AS1 inhibited the proliferation of colon cancer cells and induced growth arrest. Down-regulation of DNAJC3-AS1 also inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of colon cancer cells. Moreover, miR-214-3p can bind to DNAJC3-AS1, and knockdown of DNAJC3-AS1 increased miR-214-3p expression in colon cancer cells. LIVIN was identified as a target of miR-214-3p. The up-regulation of miR-214-3p inhibited the protein expression of LIVIN and suppressed the activation of the NF-κB signaling pathway. Besides, down-regulation of DNAJC3-AS1 reduced cell viability, invasion, and EMT of colon cancer cells, while miR-214-3p inhibitor could reverse these effects. The expression of LIVIN and the activation of the NF-κB signaling pathway were suppressed by down-regulating DNAJC3-AS1, while these effects could be restored by miR-214-3p inhibitor. These findings suggested that DNAJC3-AS1 may promote colon cancer progression by regulating the miR-214-3p/LIVIN axis. DNAJC3-AS1 may serve as a new biomarker and therapeutic target for colon cancer, stimulating new research directions and treatment options.

Associations of blood lead levels with multiple genotoxic biomarkers among workers in China: A population-based study.

Carcinogenic effects from low doses of lead (Pb) exposure to populations have been suspected but not concluded. Therefore, a large-scale cross-sectional study was conducted by us to investigate genotoxic effects from Pb exposure during 2016-2018 in North China. Blood lead levels (BLLs) and cumulative blood lead levels (CBLLs) were measured. Multiple relevant biomarkers were used to assess genotoxicity of Pb: mitochondrial DNA copy number (mtDNAcn, n = 871), Comet Tail Intensity (n = 872), γ-H2AX (n = 345), relative telomere length (rTL, n = 757), micronuclei (MN, n = 934) and phosphatidylinositol glycan class A mutation (PIG-A, n = 362). The BLL data show right-skewed distribution, with increase of the median (P25, P75) from 17.4 (8.9, 26.4) µg/dl in 2016 to 18.5 (10.5, 27.2) µg/dl in 2017, and to 20.8 (11.3, 31.0) µg/dl in 2018. Multivariate regression analyses show that mtDNAcn was non-linearly associated with BLLs or CBLLs, i.e. decreased at low levels but increased at the higher levels. Comet and Micronuclei data show positive dose-response relationships with BLLs as well as CBLLs. γ-H2AX data show an overall increased trend with BLLs while rTL data show a shortening trend. No associations were found for PIG-A mutation with Pb exposure. Our findings indicate that current low dose exposure to Pb can still cause health hazards to occupational populations, and the mechanism may be via the induction of DNA & chromosome damage rather than via the mutagenesis pathway.

Low-level lead exposure is associated with aberrant sperm quality and reproductive hormone levels in Chinese male individuals: Results from the MARHCS study low-level lead exposure is associated with aberrant sperm quality.

Studies in animals suggest an adverse effect of high-level lead exposure on male reproductive outcomes. However, evidence of the effects of low-level lead exposure is inconsistent. The purpose of our study was to explore the relationship between low-level lead exposure from daily environmental contaminants and semen quality in a community population without occupational exposure. We recruited 751 students in the Male Reproductive Health in Chongqing College Students (MARHCS) study and 190 community males from Bishan, Chongqing. Eight urinary metals (Pb, Cd, As, Cu, Zn, Ni, Mn, and Cr), semen quality, and serum sex hormones were detected. Even if the blood lead concentration was below the US lead poisoning standard for children (100 µg/L), a significant dose-response relationship was found between lead exposure and a decrease in semen quality. Multilinear regression showed that urinary Pb was negatively associated with sperm concentration, total sperm count, progressive motility and total sperm motility (regression coefficient: -0.074, -0.103, -0.024, and -0.014, respectively; p: <0.001, <0.001, 0.007, and <0.001, respectively), accompanied by decreased serum follicle-stimulating hormone, serum testosterone and the testosterone/luteinizing hormone ratio (ß coefficient: -0.090, -0.082, and -0.020, respectively; p: 0.002, <0.001, and 0.021, respectively). Logistic regression also indicated that the risk of having abnormal semen quality was higher in the high Pb group (OR: 2.501, 95% CI: 1.411, 4.435, p = 0.002) than in the low Pb group after adjusting for confounders, with a dose-response relationship in the trend test (p = 0.007). Our results revealed an inverse association between Pb exposure at low levels and semen quality.

Livin Regulates H2A.XY142 Phosphorylation and Promotes Autophagy in Colon Cancer Cells via a Novel Kinase Activity.

Objective: To investigate Livin-mediated regulation of H2A.XY142 phosphorylation via a novel kinase activity and its effect on autophagy in colon cancer cells. Methods: The interaction between Livin and H2A.X was tested by immunoprecipitation. H2A.X-/- HCT116 cells were transfected with human influenza hemagglutinin (HA)-tagged WT or Y142F phospho-dead mutantH2A.X plasmids. GST-tagged recombinant Livin protein was used to perform in vitro pull-down experiment and kinase assay. H2A.X-/-Livin+/+ SW480 cells were co-transfected with H2A.XWT/H2A.XY142F plasmid and LC3 EGFP-tagged plasmid to explore whether H2A.XY142F was involved in Livin-mediated autophagy induced by starvation in colon cancer cells. Results: Co-immunoprecipitation studies confirmed that Livin interacted with H2A.X and that it was phosphorylation dependent. In vitro kinase assay confirmed that Livin could phosphorylate H2A.X. Knockdown of Livin (Livin-/-) in SW480 cells or HCT116 cells canceled the starvation-induced autophagy in colon cancer cells; H2A.X-/-Livin+/+ SW480 cells transfected with H2A.XWT activated autophagy induced by starvation while cells transfected with H2A.XY142F had no significant difference; Livin-H2A.XY142F axis activated autophagy in colon cancer cells through transcriptionally regulating ATG5 and ATG7. Conclusion: Livin promotes autophagy in colon cancer cells via regulating the phosphorylation of H2A.XY142.

Association between GSTT1 Homozygous Deletion and Risk of Pancreatic Cancer: A Meta Analysis.

Objective To clarify the possible association of GSTT1 homozygous deletion with the susceptibility to pancreatic cancer. Methods We searched PubMed database, Chinese Journal Full Text Database (CNKI), and EMBASE to find the eligible studies published up to April 18, 2018 for evaluating the relationship between GSTT1 homozygous deletion and pancreatic cancer. The frequency of null genotype for GSTT1 between the pancreatic cancer group and the healthy control group was compared with Chi-square test, and odds ratios (ORs) value and 95% confidence interval (95% CI) were calculated. Results A total of 9 studies met the inclusion criteria, and 5952 cases consisting of 2387 pancreatic cancer patients and 3565 healthy controls were included in the meta analysis. Compared with the control group, frequency of null genotype for GSTT1 in the pancreatic cancer group was higher (33.4% vs. 38.7%, OR = 1.26, 95%CI = 1.01-1.58, P = 0.04). Conclusion GSTT1 homozygous deletion individuals may have higher susceptibility to pancreatic cancer.

Physical information of 2705 PCR-based molecular markers and the evaluation of their potential use in wheat.

Genetic information of polymerase chain reaction (PCR)-based markers, one of the main tools of genetics and genomics research in wheat, have been well documented in wheat. However, the physical position in relation to these markers has not yet been systematically characterized. Aim of this study was to characterize the physical information of thousands of widely used molecular markers.We first assigned 2705 molecular markers to wheat physical map, of which 86.1% and 84.7% were the best hits to chromosome survey sequencing (CSS) project (CSS-contigs) and International Wheat Genome Sequencing Consortium Reference Sequence v1.0 (IWGSC RefSeq v1.0), respectively. Physical position of 96.2% markers were predicated based on BLAST analysis, were in accordance with that of the previous nullisomic/aneuploidy/linkage analysis. A suggestive high-density physical map with 4643 loci was constructed, spanning 14.01 Gb (82.4%) of the wheat genome, with 3.02 Mb between adjacent markers. Both forward and reverse primer sequences of 1166 markers had consistent best hits to IWGSC RefSeq v1.0 based on BLAST analysis, and the corresponding allele sizes were characterized. A detailed physical map with 1532 loci was released, spanning 13.93 Gb (81.9%) of the wheat genome, with 9.09 Mb between adjacent markers. Characteristic of recombination rates in different chromosomal regions was discussed. In addition, markers with multiple sites were aligned to homoeologous sites with a consistent order, confirming that a collinearity existed among A, B and D subgenomes. This study facilitates the integration of physical and genetical information of molecular markers, which could be of value for use in genetics and genomics research such as gene/QTL map-based cloning and marker-assisted selection.

Livin promotes colon cancer progression by regulation of H2A.XY39ph via JMJD6.

Livin is an important member of the human inhibitor of apoptosis proteins (IAPs) family. IAPs are proteins with antiapoptotic abilities, and their functions are different from the Bcl-2 (B-cell lymphoma-2) family proteins. However, the precise role of Livin in colon cancer progression remains unclear. The purpose of this study is to assess the effect of overexpression Livin in colon cancer cells and to examine its molecular mechanism. We demonstrated that Livin induced a colon cancer phenotype, including proliferation and migration, by regulating H2A.XY39ph (histone family 2A variant (H2AX) phosphorylated on the 39th serine site). We elucidated that Livin degraded Jumonji-C domain-containing 6 protein (JMJD6), which was mediated by the proteasome murine double minute 2 (MDM2), thereby regulating H2A.XY39ph. Above all, the overexpression of JMJD6 recovered H2A.XY39ph in colon cancer cells with a high level of Livin, thus inhibiting colon cancer malignancy progression. These results reveal a previously unrecognized role for Livin in regulating the tumor-initiating capacity in colon cancer and provide a novel treatment strategy in cancer via the interruption of H2A.XY39ph function and the interaction between H2A.XY39ph and JMJD6.

The prevalence and persistence of aberrant promoter DNA methylation in benzene-exposed Chinese workers.

Aberrant DNA methylation patterns are common in cancers and environmental pollutant exposed subjects. Up to date, few studies have examined the aberrant DNA methylation patterns in benzene exposed workers. We recruited 141 benzene-exposed workers, including 83 benzene-exposed workers from a shoe factory in Wenzhou and 58 workers from a painting workshop in Wuhu, 35 workers in Wuhu were followed from 2009 to 2013, and 48 indoor workers as controls from Wenzhou. We used high-resolution melting (HRM) to quantitate human samples of DNA methylation in long interspersed nuclear element-1 (LINE-1), (6)-methylguanine-DNA methyltransferase (MGMT), and DNA mismatch repair gene human mutator L homologue 1 (hMLH1). AML-5 cells were treated with benzoquinone (BQ) and hydroquinone (HQ), and the promoter methylation of MGMT and hMLH1 was detected using the bisulfite sequencing PCR method. The degree of LINE-1 methylation in benzene-exposed workers was significantly lower than that of the controls (p<0.001), and the degree of MGMT (p<0.001) and hMLH1 (p = 0.01) methylation was significantly higher than that of the controls. The in vitro study validated the aberrant hypermethylation of hMLH1 after treatment with BQ. Among the cohort workers who were followed from 2009 to 2013, the LINE1 methylation elevated in 2013 than 2009 (p = 0.004), and premotor methylation in hMLH1 reduced in 2013 than 2009 (p = 0.045) with the reduction of the benzene exposure. This study provides evidence that benzene exposure can induce LINE-1 hypomethylation and DNA repair gene hypermethylation.

Association of BER and NER pathway polymorphism haplotypes and micronucleus frequencies with global DNA methylation in benzene-exposed workers of China: Effects of DNA repair genes polymorphisms on genetic damage.

OBJECTIVE: The base excision repair (BER) pathway and nucleotide excision repair (NER) pathway play important roles in the repair of benzene-induced genetic damage, and the effects of polymorphisms in these pathways on genetic damage and global DNA methylation are of great interest. METHODS: Ten single nucleotide polymorphisms (SNPs) in the BER (XRCC1: rs25489, rs25487; APE1: rs1130409) and NER pathways (XPA: rs1800975; XPC: rs2228000, rs2228002; XPD: rs13181, rs1799793; XPG: rs17655; ERCC1: rs3212986) were analyzed by a Kompetitive allele-specific PCR (KASP) assay to find associations with cytokinesis-block micronucleus (MN) frequency and global DNA methylation in 294 shoe factory workers and 102 control participants. RESULTS: Workers who possessed the following genotypes were associated with high MN frequency: rs25487 AA (FR (95% CI): 1.50 (1.16,1.9), p = 0.002, reference GG); rs1130409 GG (FR (95% CI): 1.28 (1.05,1.55), p = 0.010, reference TT); rs17655 GC (FR (95% CI): 1.18 (1.02,1.38), p = 0.038, reference GG); and rs3212986 TT (FR (95% CI): 1.55 (1.31,1.83), p < 0.001, reference GG). Workers with four and three mutant alleles showed 3.72-fold (OR (95% CI): 3.72 (1.34, 10.03), p = 0.009) and 2.48-fold (OR (95% CI): 2.48 (1.27, 4.88), p = 0.008) increased risk of genetic damage compared with workers with no or one mutant allele, and a dose-response relationship was found by the trend test (p = 0.006). The rs1130409 variant allele (GG+GT) was associated with low global DNA methylation (ß=-0.20, 95% CI: -0.42, 0.03, p = 0.045). CONCLUSION: In benzene-exposed workers, BER and NER pathway polymorphism haplotypes are associated with different levels of chromosome damage and had little effect on global DNA methylation.

MTHFR Gene Polymorphism Is Associated With DNA Hypomethylation and Genetic Damage Among Benzene-Exposed Workers in Southeast China.

OBJECTIVE AND METHODS: To analyze the association between global DNA methylation and single-nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR). MTHFR polymorphisms rs1801133 and rs1801131 were detected using the restriction fragment length polymorphism method, and cytokinesis-block micronucleus (MN) frequency and global DNA methylation was measured in workers from 410 shoe factories. RESULTS: A multilinear regression analysis demonstrated that DNA methylation of the TT variant allele of rs1801133 was lower than that of the CC wild type allele (Exp(ß) [95% CI], 0.76 [0.56, 1.02], P = 0.071), with a P-value approaching significance. A significantly increased MN frequency was observed for carriers of the TT genotype (frequency ratio = 1.27, 95% CI: 1.07-1.51, P < 0.01). CONCLUSION: The results imply that the TT genotype in rs1801133 is associated with global DNA hypomethylation, which may influence the induction of MN following exposure to benzene.

Overexpression of Livin promotes migration and invasion of colorectal cancer cells by induction of epithelial-mesenchymal transition via NF-κB activation.

Livin is a novel member of the inhibitors of apoptosis protein family and has been implicated in the development and progression of colorectal cancer (CRC). However, the underlying mechanisms of Livin in CRC remain not fully understood. In this study, we investigated the effects of Livin expression on the proliferation and metastasis of CRC cells and also addressed its related molecular mechanism to metastasis. The expression of Livin in CRC cells (HCT116, SW480, and HT-29 cell lines) was determined by Western blot analysis. Our results show that the overexpression of Livin significantly promotes the proliferation, migration, and invasion of SW480 cells. Concurrently, the inhibition of Livin reduces the proliferation, migration, and invasion of HCT116 cells. In addition, Livin overexpression promotes the epithelial-mesenchymal transition, as evidenced by a decrease in epithelial E-cadherin expression and an increase in mesenchymal markers, including vimentin, Slug, and Snail. Furthermore, adding the NF-κB inhibitor, BAY 11-7028, or transfecting with small interfering RNA against p65 notably restores the expression level of E-cadherin and attenuates the invasive ability of Livin-overexpressing cells. Taken together, these results indicate that Livin potentiates migration and invasion of CRC cells partially through the induction of epithelial-mesenchymal transition via NF-κB activation. Livin may be a potential therapeutic target for CRC.