AIM: To investigate the presence of human papillomavirus(HPV) DNA along with the integration,the quantification and the expression of the HPV16 in colorectal cancers.METHODS: A prospective series of colorectal tumors ...AIM: To investigate the presence of human papillomavirus(HPV) DNA along with the integration,the quantification and the expression of the HPV16 in colorectal cancers.METHODS: A prospective series of colorectal tumors were genotyped for HPV DNA.The clinical and pathological variables of the HPV-positive tumors were compared to those of HPV-negative samples.The integration status of HPV16 was evaluated by calculating E2/E6 ng ratios.HPV16-positive tumors were also evaluated for(1) E2,E4,E5,E6 and E7 viral gene ng quantification;(2) relative quantification compared to W12 cells; and(3) viral E2,E4,E5,E6 and E7 mR NA transcripts by real-time polymerase chain reaction.RESULTS: HPV infection was detected in 16.9% of all tumors examined,and HPV16 was the most frequent type detected(63.6% of positive tissues).Notably,the clinical and pathological features of HPV-positive colorectal cancers were not significantly different than those of HPV-negative cancers(χ2 and t-test for all clinical and pathological features of HPV-positive vs HPV-negative colorectal cancers: p ns).HPV16 DNA was present exclusively in episomal form,and the HPV16 E2,E4,E5,E6 and E7 genes were detected in tracenanogram quantities.Furthermore,the HPV16 genes ranged from 10-3 to 10-9 compared to W12 cells at an episomal stage.Although the extractions were validated by housekeeping gene expression,all the HPV16 positive tissues were transcriptionally inactive for the E2,E4,E5,E6 and E7 mR NAs.CONCLUSION: Based on our results,HPV is unlikely involved in colorectal carcinogenesis.展开更多
Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. The interplay of genetic susceptibility, infections, and life style factors has been propos...Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. The interplay of genetic susceptibility, infections, and life style factors has been proposed to be responsible for carcinogenesis of gallbladder. Persistence of infection leading to chronic inflammation, and production of certain toxins and metabolites with carcinogenic potentials, by certain bacteria has been speculated to be involved in the transformation of the gallbladder epithelium. Therefore, any bacteria that have evolved to acquire both of the above carcinogenic mechanisms can cause cancer. Salmonella typhi has been found to be prominently associated with CaGB. Chronic typhoid carriage (persistence) and production of mediators of chronic infl ammation and a genotoxic toxin (cytotoxic distending toxin, CdtB) are also known for this bacterium. Furthermore, the natural concentrating function of the gallbladder might amplify the carcinogenic effect of the mediators of carcinogenesis. In addition to S. typhi, certain species of Helicobacter (H. bilis and H. hepaticus) and Escherichia coli have also been implicated in carcinogenesis. As the isolation rate is verypoor with the presently available culture techniques, the existence of bacteria in a viable but non-cultivable state is quite likely; therefore, sensitive and specif ic molecular techniques might reveal the etiological role of bacterial infection in gallbladder carcinogenesis. If bacteria are found to be causing cancers, then eradication of such infections might help in reducing the incidence of some cancers.展开更多
INTRODUCTIONHepatocellular carcinoma (HCC) is one of themajor cancers in the world with a mortality of morethan 250 000 cases yearly.More than 137 000 casesof HCC were diagnosed each year in China,whichacount approxim...INTRODUCTIONHepatocellular carcinoma (HCC) is one of themajor cancers in the world with a mortality of morethan 250 000 cases yearly.More than 137 000 casesof HCC were diagnosed each year in China,whichacount approximately for more than 40 percent ofthe total number in the world.HCC has become thesecond major cause of death for cancer in展开更多
Dear Editor,On March 8–15,2022,a board of international scientists assembled in Lyon to evaluate the carcinogenicity of cobalt metal,cobalt(Ⅱ)salts,antimony trioxide,and weaponsgrade tungsten alloy harboring nickel ...Dear Editor,On March 8–15,2022,a board of international scientists assembled in Lyon to evaluate the carcinogenicity of cobalt metal,cobalt(Ⅱ)salts,antimony trioxide,and weaponsgrade tungsten alloy harboring nickel and cobalt[1].The 131st International Agency for Research on Cancer(IARC)Monograph is the result of a 6–9-month work of perusing the literature,slide evaluation,data interpretation,and interim meetings.The assessment of cobalt,antimony,and nickelcontaining alloys will have tremendous consequences for the industry,health,and defense departments[1].展开更多
Fish constitutes the main protein source for the Amazonian population.However,the impact of different anthropogenic activities on trace element and metal accumulation in fish and their risks for human health at a regi...Fish constitutes the main protein source for the Amazonian population.However,the impact of different anthropogenic activities on trace element and metal accumulation in fish and their risks for human health at a regional scale remain largely unexplored.Here we assessed exposure levels of 10 trace elements andmetals(Cr,Mn,Fe,Ni,Cu,Zn,As,Cd,Pb,and Hg)in 56 samples belonging to 11 different species of fish from the Brazilian Amazon.We studied the relationship between exposure levels,fish origin,and fish feeding habits,and assessed toxicological and carcinogenic risks for the Amazonian population.No significant correlation was found between sampling site and exposure levels to the studied elements,but a significant difference was found between the accumulation of some metals and the position of the fish species in the food chain.The concentrations of Cr and Hg in fish flesh were found to exceed the Brazilian limits for human consumption.This study shows that current fish consumption patterns can lead to estimated daily intakes of Hg,As and Cr that exceed the oral reference dose,thus posing a toxicological concern.Furthermore,carcinogenic risks may be expected due to the continued exposure to Cr and As.The results of this study show that the consumption of wild caught fish in the Amazon region should be controlled.Moreover,continued monitoring of trace element and metal contamination in fish and on the health of the Amazonian population is recommended,particularly for riverine and indigenous communities.展开更多
Pollution of transboundary rivers can result from anthropogenic activities in their watersheds.In this study,sediment traps were deployed to determine the fluxes,concentrations,and health risks associated with arsenic...Pollution of transboundary rivers can result from anthropogenic activities in their watersheds.In this study,sediment traps were deployed to determine the fluxes,concentrations,and health risks associated with arsenic,cadmium,mercury,lead,and iron in the estuaries of three transboundary rivers(Comoé,Bia,and Tanoé)in West Africa.Thus,the analysis of metal-associated sedimentation particle samples collected in rainy,flood,and dry seasons was required.Sediment traps were used to calculate the metal fluxes associated with sedimentation particles towards the Atlantic Ocean.Finally,the carcinogenic and non-carcinogenic risks of ingestion and dermal contact associated with sedimentation particles were assessed.The results showed that the total concentrations of trace metals in particulate matter were higher than in the UCC(Upper Crust Continental),with the exception of lead.The highest fluxes of lead,mercury,iron and arsenic associated with sedimented particles were observed during flood periods in the estuary of the Comoé,Bia and Tanoérivers.Cadmium fluxes associated with sedimentation particles were highest in the rainy season in the Bia and Comoéestuaries and in the flood season in the Tanoéestuary.Pearson’s correlation analysis and the enrichment factor showed that the trace metals were derived from anthropogenic activities such as mining and farming.In addition,contamination indices showed that sediment particles in the estuaries of the three rivers were severely contaminated with mercury.However,the results of potential human health risks associated with trace metals show that there is no probability of exposure of the community to harmful and carcinogenic effects through ingestion and dermal absorption of sediment particles.It is essential to integrate the information from this study into policy-and decision-making processes for better management of transboundary river water resources in coastal countries,particularly the Côte d’Ivoire.展开更多
Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly ...Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).展开更多
Long-term mining activities can result in the release of heavy metals into soil,ultimately posing a threat to human health.In arid and semi-arid regions,wind-driven transport of these toxic metals from mining areas re...Long-term mining activities can result in the release of heavy metals into soil,ultimately posing a threat to human health.In arid and semi-arid regions,wind-driven transport of these toxic metals from mining areas represents a primary mechanism for their spatial distribution.To evaluate pollution levels and associated health risks of eight metals,A total of 95 soil samples,corresponding 25 vegetable samples and 3 tailing samples were collected from various land types surrounding a typical Pb-Zn mine in northern China’s semi-arid region.The mean concentrations of As,Cd,Cr,Cu,Hg,Ni,Pb and Zn in soils were 62.8,0.27,29.6,11.5,0.02,14.4,49.9 and 109.5 mg/kg,respectively.Among these,As,Cd,Pb,and Zn emerged as the predominant pollutants,with some samples exceeding national risk screening values.The results of contamination factor(CF),pollution load index(PLI)and geo-accumulation index(I_(geo))indicated that heavy metals in most soils exhibited non-polluted level or slight pollution level,though localized severe contamination by As,Cd,Pb,and Zn was observed.Spatial distribution analysis demonstrated similar dispersion patterns for As,Cd,Pb,and Zn,with wind-mediated transport extending up to 2.0 km from contamination sources.Pearson’s correlation analysis and principal component analysis(PCA)suggested that As,Cd,Pb and Zn mainly originated from mining activities,and Cr,Ni,Cu and Hg derived from soil parent materials.All vegetable samples contained metal concentrations below food safety thresholds.Health risk assessment showed hazard quotient(HQ)values for individual metals below 1 across all exposure groups,indicating negligible non-carcinogenic risk.Similarly,carcinogenic risk(CR)values for As,Cd,Cr,and Pb fell within acceptable ranges.While mining activities have induced significant localized contamination,the overall affected area remains limited in arid and semi-arid regions.However,greater attention should be directed toward potential health implications from vegetable consumption in proximity to mining operations within arid and semi-arid regions.展开更多
Xining,a river valley city in China’s arid region,serves as an important industrial hub with a fragile ecological environment.While groundwater heavy metal pollution in this area has drawn increasing concern,the sour...Xining,a river valley city in China’s arid region,serves as an important industrial hub with a fragile ecological environment.While groundwater heavy metal pollution in this area has drawn increasing concern,the sources and associated human health risks remain inadequately understood.This study analyzed 144 shallow groundwater samples from urban Xining for 14 heavy metals(Fe,Al,B,Mn,Ba,Zn,Pb,Cr^(6+),Ni,Cu,Co,Sb,Cd,and As)using the Nemerow comprehensive pollution index,correlation analysis,and the USEPA health risk assessment model.Results identified Fe,Al,B,Mn,Ba,Pb,Cd,and As as the primary pollutants,especially concentrated in river valley plains.These contaminants primarily originate from natural sedimentary conditions and human activities such as industrial and agricultural development.The pollution indices for Al,Pb,Mn,and Fe exceeded clean water thresholds,indicating serious contamination and the need for enhanced regulation.Health risk assessments revealed that children face greater exposure risks than adults,with arsenic and nickel being the main contributors to carcinogenic risk.Sensitivity analysis further showed that As,Fe,and Cd posed the greatest non-carcinogenic and carcinogenic risks,particularly in human-impacted areas such as the Nanchuan and Beichuan valleys and Ganhegou.These findings provide essential insights for groundwater safety management in plateau river valley cities and similar vulnerable regions.展开更多
Objective: To investigate the expression of cyclooxy- genase-1 (COX-1) and cyclooxygenase-2 (COX-2) in extra-hepatic cholangiocarcinoma and the relation- ship between their expression and clinicopathological parameter...Objective: To investigate the expression of cyclooxy- genase-1 (COX-1) and cyclooxygenase-2 (COX-2) in extra-hepatic cholangiocarcinoma and the relation- ship between their expression and clinicopathological parameters. Methods: COX-1 and COX-2 were detected in 56 ex- tra-hepatic cholangiocarcinomas, including 31 matched tissues originating from non-tumorous bile ductal tissue adjacent to tumours and 6 normal bile ductal tissues, by immunohistochemistry strept avi- din-biotin complex using isozyme selective antibod- ies. Results: There was no difference in expression of COX-1 between carcinomas (96%, 54/56) and non- cancerous specimens (94%, 29/31, P>0.05) or normal bile ductal tissues (100%, 6/6, P>0.05). The positive rate of COX-2 expression in extra-hepat- ic cholangiocarcinomas (86%, 48/56) was signifi- cantly higher than their matched tissues (39%, 12/ 31, P<0.01) and normal bile ductal tissues (0%, 0/6, P<0.01). Overexpression of COX-2 in extra- hepatic cholangiocarcinoma was related to the metas- tasis of lymph nodes, distant organs or tissues (P< 0.05) as well as the degree of tumour differentiation (P<0.05). Conclusions: The overexpression of COX-2 plays a crucial role in the carcinogenesis and development of extra-hepatic cholangiocarcinoma, indicating that COX-2 may serve as a target for chemoprevention of extra-hepatic cholangiocarcinoma.展开更多
Although mutations clearly play a role in themulti-stage process of carcinogenesis,a challengewll be made to the paradigm that most chemical"carcinogens" act via mutagenic activity("carcinogens as mutag...Although mutations clearly play a role in themulti-stage process of carcinogenesis,a challengewll be made to the paradigm that most chemical"carcinogens" act via mutagenic activity("carcinogens as mutagens").Control ofproliferation and differentiation within andbetween tissues is mediated by展开更多
The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to ...The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.展开更多
AIM To explore the relationship betweenconsumption of fish sauce and the risk of gastriccancer in Fujian Province.METHODS An ecological study was carriedout.A total of 11000 subjects from 55 townshipswere randomly sel...AIM To explore the relationship betweenconsumption of fish sauce and the risk of gastriccancer in Fujian Province.METHODS An ecological study was carriedout.A total of 11000 subjects from 55 townshipswere randomly selected from 10 counties withinFujian Province.All subjects were localresidents who had been living in Fujian Provincefor more than 20 years,within the age group of45-74 years.Trained interviewers conductedface-to-face interviews with a standardizedquestionnaire,which covered the frequency andamount of food intake,dietary habit,tobaccoand alcohol consumption and history of chronicgastric diseases.Univariate and multivariateanalyses were performed using Epi-info and SASstatistical packages,respectively.RESULTS A significant correlation betweenmonthly consumption of fish sauce and mortalityof gastric cancer was found.Pearson’scoefficient of correlation was statisticallysignificant with r=0.7356 for males,r=0.5246for females(P【0.01).In the multivariateanalysis,consumption of fish sauce still showedan association with the risk of gastric cancer.No significant positive correlation betweenesophagus cancer,liver cancer,colon cancerand consumption of fish sauce were observed.CONCLUSION Long-term intake of fish saucemay be related to high mortality of gastriccancer.Consumption of fish sauce might be oneof important and unique etiologic factors ofgastric cancer in Fujian Province.Furtherstudies are needed to confirm this ecologicalstudy.展开更多
AIM: Hypermethylation of the promoter of the hMLH1gene, which plays an important role in mismatch repair during DNA replication, occurs in more than 30% of human gastric cancer tissues. The purpose of this study was t...AIM: Hypermethylation of the promoter of the hMLH1gene, which plays an important role in mismatch repair during DNA replication, occurs in more than 30% of human gastric cancer tissues. The purpose of this study was to investigate the effects of environmental factors, genetic polymorphisms of major metabolic enzymes, and microsatellite instability on hypermethylation of the promoter of the hMLH1 gene in gastric cancer.METHODS: Data were obtained from a hospital-based,case-control study of gastric cancer. One hundred and ten gastric cancer patients and 220 age- and sex-matched control patients completed a structured questionnaire regarding their exposure to environmental risk factors.Hypermethylation of the hMLH1 gene promoter,polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1,ALDH2 and L-myc genes, microsatellite instability and mutations of p53 and Ki-ras genes were investigated.RESULTS: Both smoking and alcohol consumption were associated with a higher risk of gastric cancer with hypermethylation of the hMLH1 gene promoter. High intake of vegetables and low intake of potato were associated with increased likelihood of gastric cancer with hypermethylation of the hMLH1 gene promoter. Genetic polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1,ALDH2, and L-mycgenes were not significantly associated with the risk of gastric cancer either with or without hypermethylation in the promoter of the hMLH1 gene.Hypermethylation of the hMLH1 promoter was significantly associated with microsatellite instability (MSI): 10 of the 14 (71.4%) MSI-positive tumors showed hypermethylation,whereas 28 of 94 (29.8%) the MSI-negative tumors were hypermethylated at the hMLH1 promoter region.Hypermethylation of the hMLH1 gene promoter was significantly inversely correlated with mutation of the p53gene.CONCLUSION: These results suggest that cigarette smoking and alcohol consumption may influence the development of hMLH1-positive gastric cancer. Most dietary factors and polymorphisms of GSTM1, GSTT1,CYP1A1, CYP2E1, ALDH2, and L-myc genes are not independent risk factors for gastric cancer with hypermethylation of the hMLH1 promoter. These data also suggest that there could be two or more different molecular pathways in the development of gastric cancer, perhaps involving tumor suppression mechanisms or DNA mismatch repair.展开更多
INTRODUCTIONChina is a country with a high incidence of liver cancer insome areas.Liver cancer has a wide distribution andthreatens human health seriously.A rough estimationshows that out of a population of 1.2×1...INTRODUCTIONChina is a country with a high incidence of liver cancer insome areas.Liver cancer has a wide distribution andthreatens human health seriously.A rough estimationshows that out of a population of 1.2×10~8 in liver展开更多
The concentration of carcinogenic polycyclic aromatic hydrocarbons （c-PAHs） present in the sediment and water of Peninsular Malaysia as well as in the cockle Anadara granosa was investigated. Samples were extracted ...The concentration of carcinogenic polycyclic aromatic hydrocarbons （c-PAHs） present in the sediment and water of Peninsular Malaysia as well as in the cockle Anadara granosa was investigated. Samples were extracted and analysed with gas chromatographymass spectrometry. The concentrations of total carcinogenic polycyclic aromatic hydrocarbons （t-PAHs） were measured between 0.80±0.04 to 162.96 ±14.74 ng/g wet weight （ww） in sediment, between 21.85± 2.18 to 76.2± 10.82 ng/L in water samples and between 3.34 ±0.77 to 46.85 ± 5.50 ng/g ww in the cockle tissue. The risk assessment of probable human carcinogens in the Group B2 PAHs was calculated and assessed in accordance with the standards of the United States Environmental Protection Agency （US EPA）. Case I in the toxicity assessment analysed the cancer risk to consumers of Malaysian blood cockle. Case II assessed the risk of cancer from exposure to PAHs from multiple pathways. The average cancer risk of case I and case II were found to be classifiable as unsafe according to the US EPA standard. The cancer risk due to c-PAHs acquired by the ingestion of blood cockle was （8.82 ± 0.54） × 10^ 6 to （2.67 ± 0.06） × 10^-2, higher than the US EPA risk management criterion. The non-cancer risks associated with multiple pathways in Kuala Gula, Kuala Juru and Kuala Perlis were higher than the US EPA safe level, but the non-cancer risk for eating blood cockle was below the level of US EPA concern.展开更多
Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric c...Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.展开更多
AIM： To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity o...AIM： To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma （ESCC） among the Kashmiri population of Northern India. METHODS： All cases （n = 51） and controls （n = 150） were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases （n = 45） and inpatient controls （n = 150） with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient＇s age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls.RESULTS： Thirty-five of 45 （77.8%） histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed gerrnline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 （77.7%）, that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance （P 〈 0.05） with familial history of cancer （CD = 58）, suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable ＂Hakh＂ （CD = 19.5）, red chillies （CD = 20.2）, hot salty soda tea （CD = 2.37） and local baked bread （CD = 1.1）. CONCLUSION： Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and ＂Hakh＂, that are rich in nitrosoamines and familial cancer history.展开更多
Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of h...Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas.展开更多
Urbanization may cause increased exposure levels to polycyclic aromatic hydrocarbons （PAHs） and associated health risks for over half of the world＇s population living in cities, but little evidence has shown a dire...Urbanization may cause increased exposure levels to polycyclic aromatic hydrocarbons （PAHs） and associated health risks for over half of the world＇s population living in cities, but little evidence has shown a direct spatial relationship between urbanization and soil PAH pollution. Based on the monitored PAH concentrations in 188 topsoil （0-5 cm） samples in Shenzhen, the most rapidly developing city in China, in recent decades, we applied geographical demarcation to determine the occurrences, source apportionments, and spatial ecological risks of soil PAHs across five zones of varying urban densities. Mean concentrations of the 16 US Environmental Protection Agency （EPA） priority PAHs （∑16PAHs） and the 7 carcinogenic PAHs （2E7CarPAHs） both followed the order： Zone D （60%-80% constructive land density （CLD）） 〉 Zone E （80%-100% CLD） 〉 Zone C （40%-60% CLD） 〉 Zone B （20%-40% CLD） 〉 Zone A （0%-20% CLD）, suggesting that the highest PAH levels occurred in the suburban-urban center transitional zone （Zone D） rather than the urban center zone （Zone E） in Shenzhen. There were significant correlations of ∑16PAHs to TOC and sampling altitude across all samples but not within highly-urbanized regions （Zones D and E）, implying a considerable disturbance of urbanization to the soil PAH pool. Source apportionments suggested that soil PAHs of all zones were mainly derived from fossil fuel combustion, with Zone E showing the highest contribution from oil sources among different zones. Spatial ecological risk analysis showed that the contaminated area （467 km2; 23.9% of total area; toxic equivalency quotients 〉 33 ng g^-1） had a higher contribution from the highly-urbanized regions （Zones D and E） than the uncontaminated area （42.3% vs. 18.1%）. Overall, our study highlighted a strong spatial relationship between urbanization and soil PAH pollution.展开更多
基金Supported by The PhD University Grant program"Clinical and Experimental Research Methodologies in Oncology"provided by the Faculty of Medicine and Psychology University of Rome"La Sapienza"to Lorenzon LMIUR and AIRC-Associazione Italiana per la Ricerca sul Cancro(IG 10272),Italy
文摘AIM: To investigate the presence of human papillomavirus(HPV) DNA along with the integration,the quantification and the expression of the HPV16 in colorectal cancers.METHODS: A prospective series of colorectal tumors were genotyped for HPV DNA.The clinical and pathological variables of the HPV-positive tumors were compared to those of HPV-negative samples.The integration status of HPV16 was evaluated by calculating E2/E6 ng ratios.HPV16-positive tumors were also evaluated for(1) E2,E4,E5,E6 and E7 viral gene ng quantification;(2) relative quantification compared to W12 cells; and(3) viral E2,E4,E5,E6 and E7 mR NA transcripts by real-time polymerase chain reaction.RESULTS: HPV infection was detected in 16.9% of all tumors examined,and HPV16 was the most frequent type detected(63.6% of positive tissues).Notably,the clinical and pathological features of HPV-positive colorectal cancers were not significantly different than those of HPV-negative cancers(χ2 and t-test for all clinical and pathological features of HPV-positive vs HPV-negative colorectal cancers: p ns).HPV16 DNA was present exclusively in episomal form,and the HPV16 E2,E4,E5,E6 and E7 genes were detected in tracenanogram quantities.Furthermore,the HPV16 genes ranged from 10-3 to 10-9 compared to W12 cells at an episomal stage.Although the extractions were validated by housekeeping gene expression,all the HPV16 positive tissues were transcriptionally inactive for the E2,E4,E5,E6 and E7 mR NAs.CONCLUSION: Based on our results,HPV is unlikely involved in colorectal carcinogenesis.
文摘Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. The interplay of genetic susceptibility, infections, and life style factors has been proposed to be responsible for carcinogenesis of gallbladder. Persistence of infection leading to chronic inflammation, and production of certain toxins and metabolites with carcinogenic potentials, by certain bacteria has been speculated to be involved in the transformation of the gallbladder epithelium. Therefore, any bacteria that have evolved to acquire both of the above carcinogenic mechanisms can cause cancer. Salmonella typhi has been found to be prominently associated with CaGB. Chronic typhoid carriage (persistence) and production of mediators of chronic infl ammation and a genotoxic toxin (cytotoxic distending toxin, CdtB) are also known for this bacterium. Furthermore, the natural concentrating function of the gallbladder might amplify the carcinogenic effect of the mediators of carcinogenesis. In addition to S. typhi, certain species of Helicobacter (H. bilis and H. hepaticus) and Escherichia coli have also been implicated in carcinogenesis. As the isolation rate is verypoor with the presently available culture techniques, the existence of bacteria in a viable but non-cultivable state is quite likely; therefore, sensitive and specif ic molecular techniques might reveal the etiological role of bacterial infection in gallbladder carcinogenesis. If bacteria are found to be causing cancers, then eradication of such infections might help in reducing the incidence of some cancers.
文摘INTRODUCTIONHepatocellular carcinoma (HCC) is one of themajor cancers in the world with a mortality of morethan 250 000 cases yearly.More than 137 000 casesof HCC were diagnosed each year in China,whichacount approximately for more than 40 percent ofthe total number in the world.HCC has become thesecond major cause of death for cancer in
文摘Dear Editor,On March 8–15,2022,a board of international scientists assembled in Lyon to evaluate the carcinogenicity of cobalt metal,cobalt(Ⅱ)salts,antimony trioxide,and weaponsgrade tungsten alloy harboring nickel and cobalt[1].The 131st International Agency for Research on Cancer(IARC)Monograph is the result of a 6–9-month work of perusing the literature,slide evaluation,data interpretation,and interim meetings.The assessment of cobalt,antimony,and nickelcontaining alloys will have tremendous consequences for the industry,health,and defense departments[1].
基金supported by the National Geographic Society through an early career grant to A.Rico (EC-59809C-19)Support Programme-PlanGenT (CIDEGENT/2020/043)of the Generalitat ValencianaR.Oliveira acknowledges"Fundacao de Amparo a Pesquisa do Estado de Sao Paulo"-FAPESP (Project 2018/03108-0).
文摘Fish constitutes the main protein source for the Amazonian population.However,the impact of different anthropogenic activities on trace element and metal accumulation in fish and their risks for human health at a regional scale remain largely unexplored.Here we assessed exposure levels of 10 trace elements andmetals(Cr,Mn,Fe,Ni,Cu,Zn,As,Cd,Pb,and Hg)in 56 samples belonging to 11 different species of fish from the Brazilian Amazon.We studied the relationship between exposure levels,fish origin,and fish feeding habits,and assessed toxicological and carcinogenic risks for the Amazonian population.No significant correlation was found between sampling site and exposure levels to the studied elements,but a significant difference was found between the accumulation of some metals and the position of the fish species in the food chain.The concentrations of Cr and Hg in fish flesh were found to exceed the Brazilian limits for human consumption.This study shows that current fish consumption patterns can lead to estimated daily intakes of Hg,As and Cr that exceed the oral reference dose,thus posing a toxicological concern.Furthermore,carcinogenic risks may be expected due to the continued exposure to Cr and As.The results of this study show that the consumption of wild caught fish in the Amazon region should be controlled.Moreover,continued monitoring of trace element and metal contamination in fish and on the health of the Amazonian population is recommended,particularly for riverine and indigenous communities.
文摘Pollution of transboundary rivers can result from anthropogenic activities in their watersheds.In this study,sediment traps were deployed to determine the fluxes,concentrations,and health risks associated with arsenic,cadmium,mercury,lead,and iron in the estuaries of three transboundary rivers(Comoé,Bia,and Tanoé)in West Africa.Thus,the analysis of metal-associated sedimentation particle samples collected in rainy,flood,and dry seasons was required.Sediment traps were used to calculate the metal fluxes associated with sedimentation particles towards the Atlantic Ocean.Finally,the carcinogenic and non-carcinogenic risks of ingestion and dermal contact associated with sedimentation particles were assessed.The results showed that the total concentrations of trace metals in particulate matter were higher than in the UCC(Upper Crust Continental),with the exception of lead.The highest fluxes of lead,mercury,iron and arsenic associated with sedimented particles were observed during flood periods in the estuary of the Comoé,Bia and Tanoérivers.Cadmium fluxes associated with sedimentation particles were highest in the rainy season in the Bia and Comoéestuaries and in the flood season in the Tanoéestuary.Pearson’s correlation analysis and the enrichment factor showed that the trace metals were derived from anthropogenic activities such as mining and farming.In addition,contamination indices showed that sediment particles in the estuaries of the three rivers were severely contaminated with mercury.However,the results of potential human health risks associated with trace metals show that there is no probability of exposure of the community to harmful and carcinogenic effects through ingestion and dermal absorption of sediment particles.It is essential to integrate the information from this study into policy-and decision-making processes for better management of transboundary river water resources in coastal countries,particularly the Côte d’Ivoire.
基金National Key R&D Program of China,Grant/Award Number:2023YFC3402000National Institutes for Food and Drug Control,State Key Laboratory of Drug Regulatory Science,Grant/Award Number:2023SKLDRS0124。
文摘Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).
基金financially supported by the Institute of Mineral Resources,CAGS Research Fund(KK2416)National Natural Science Foundation of China(41807134),China Geological Survey(DD20190182).
文摘Long-term mining activities can result in the release of heavy metals into soil,ultimately posing a threat to human health.In arid and semi-arid regions,wind-driven transport of these toxic metals from mining areas represents a primary mechanism for their spatial distribution.To evaluate pollution levels and associated health risks of eight metals,A total of 95 soil samples,corresponding 25 vegetable samples and 3 tailing samples were collected from various land types surrounding a typical Pb-Zn mine in northern China’s semi-arid region.The mean concentrations of As,Cd,Cr,Cu,Hg,Ni,Pb and Zn in soils were 62.8,0.27,29.6,11.5,0.02,14.4,49.9 and 109.5 mg/kg,respectively.Among these,As,Cd,Pb,and Zn emerged as the predominant pollutants,with some samples exceeding national risk screening values.The results of contamination factor(CF),pollution load index(PLI)and geo-accumulation index(I_(geo))indicated that heavy metals in most soils exhibited non-polluted level or slight pollution level,though localized severe contamination by As,Cd,Pb,and Zn was observed.Spatial distribution analysis demonstrated similar dispersion patterns for As,Cd,Pb,and Zn,with wind-mediated transport extending up to 2.0 km from contamination sources.Pearson’s correlation analysis and principal component analysis(PCA)suggested that As,Cd,Pb and Zn mainly originated from mining activities,and Cr,Ni,Cu and Hg derived from soil parent materials.All vegetable samples contained metal concentrations below food safety thresholds.Health risk assessment showed hazard quotient(HQ)values for individual metals below 1 across all exposure groups,indicating negligible non-carcinogenic risk.Similarly,carcinogenic risk(CR)values for As,Cd,Cr,and Pb fell within acceptable ranges.While mining activities have induced significant localized contamination,the overall affected area remains limited in arid and semi-arid regions.However,greater attention should be directed toward potential health implications from vegetable consumption in proximity to mining operations within arid and semi-arid regions.
基金supported by the projects of the Geological Survey(DD20240501104,DD20230422).
文摘Xining,a river valley city in China’s arid region,serves as an important industrial hub with a fragile ecological environment.While groundwater heavy metal pollution in this area has drawn increasing concern,the sources and associated human health risks remain inadequately understood.This study analyzed 144 shallow groundwater samples from urban Xining for 14 heavy metals(Fe,Al,B,Mn,Ba,Zn,Pb,Cr^(6+),Ni,Cu,Co,Sb,Cd,and As)using the Nemerow comprehensive pollution index,correlation analysis,and the USEPA health risk assessment model.Results identified Fe,Al,B,Mn,Ba,Pb,Cd,and As as the primary pollutants,especially concentrated in river valley plains.These contaminants primarily originate from natural sedimentary conditions and human activities such as industrial and agricultural development.The pollution indices for Al,Pb,Mn,and Fe exceeded clean water thresholds,indicating serious contamination and the need for enhanced regulation.Health risk assessments revealed that children face greater exposure risks than adults,with arsenic and nickel being the main contributors to carcinogenic risk.Sensitivity analysis further showed that As,Fe,and Cd posed the greatest non-carcinogenic and carcinogenic risks,particularly in human-impacted areas such as the Nanchuan and Beichuan valleys and Ganhegou.These findings provide essential insights for groundwater safety management in plateau river valley cities and similar vulnerable regions.
文摘Objective: To investigate the expression of cyclooxy- genase-1 (COX-1) and cyclooxygenase-2 (COX-2) in extra-hepatic cholangiocarcinoma and the relation- ship between their expression and clinicopathological parameters. Methods: COX-1 and COX-2 were detected in 56 ex- tra-hepatic cholangiocarcinomas, including 31 matched tissues originating from non-tumorous bile ductal tissue adjacent to tumours and 6 normal bile ductal tissues, by immunohistochemistry strept avi- din-biotin complex using isozyme selective antibod- ies. Results: There was no difference in expression of COX-1 between carcinomas (96%, 54/56) and non- cancerous specimens (94%, 29/31, P>0.05) or normal bile ductal tissues (100%, 6/6, P>0.05). The positive rate of COX-2 expression in extra-hepat- ic cholangiocarcinomas (86%, 48/56) was signifi- cantly higher than their matched tissues (39%, 12/ 31, P<0.01) and normal bile ductal tissues (0%, 0/6, P<0.01). Overexpression of COX-2 in extra- hepatic cholangiocarcinoma was related to the metas- tasis of lymph nodes, distant organs or tissues (P< 0.05) as well as the degree of tumour differentiation (P<0.05). Conclusions: The overexpression of COX-2 plays a crucial role in the carcinogenesis and development of extra-hepatic cholangiocarcinoma, indicating that COX-2 may serve as a target for chemoprevention of extra-hepatic cholangiocarcinoma.
文摘Although mutations clearly play a role in themulti-stage process of carcinogenesis,a challengewll be made to the paradigm that most chemical"carcinogens" act via mutagenic activity("carcinogens as mutagens").Control ofproliferation and differentiation within andbetween tissues is mediated by
文摘The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.
基金Natural Science Foundation of Fujian Province,China,No.K98036
文摘AIM To explore the relationship betweenconsumption of fish sauce and the risk of gastriccancer in Fujian Province.METHODS An ecological study was carriedout.A total of 11000 subjects from 55 townshipswere randomly selected from 10 counties withinFujian Province.All subjects were localresidents who had been living in Fujian Provincefor more than 20 years,within the age group of45-74 years.Trained interviewers conductedface-to-face interviews with a standardizedquestionnaire,which covered the frequency andamount of food intake,dietary habit,tobaccoand alcohol consumption and history of chronicgastric diseases.Univariate and multivariateanalyses were performed using Epi-info and SASstatistical packages,respectively.RESULTS A significant correlation betweenmonthly consumption of fish sauce and mortalityof gastric cancer was found.Pearson’scoefficient of correlation was statisticallysignificant with r=0.7356 for males,r=0.5246for females(P【0.01).In the multivariateanalysis,consumption of fish sauce still showedan association with the risk of gastric cancer.No significant positive correlation betweenesophagus cancer,liver cancer,colon cancerand consumption of fish sauce were observed.CONCLUSION Long-term intake of fish saucemay be related to high mortality of gastriccancer.Consumption of fish sauce might be oneof important and unique etiologic factors ofgastric cancer in Fujian Province.Furtherstudies are needed to confirm this ecologicalstudy.
基金Supported by the Korea Health 21 R and D Project, Ministry of Health and Welfare, Republic of Korea. No. 00-PJ1-PG3-21900-0008
文摘AIM: Hypermethylation of the promoter of the hMLH1gene, which plays an important role in mismatch repair during DNA replication, occurs in more than 30% of human gastric cancer tissues. The purpose of this study was to investigate the effects of environmental factors, genetic polymorphisms of major metabolic enzymes, and microsatellite instability on hypermethylation of the promoter of the hMLH1 gene in gastric cancer.METHODS: Data were obtained from a hospital-based,case-control study of gastric cancer. One hundred and ten gastric cancer patients and 220 age- and sex-matched control patients completed a structured questionnaire regarding their exposure to environmental risk factors.Hypermethylation of the hMLH1 gene promoter,polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1,ALDH2 and L-myc genes, microsatellite instability and mutations of p53 and Ki-ras genes were investigated.RESULTS: Both smoking and alcohol consumption were associated with a higher risk of gastric cancer with hypermethylation of the hMLH1 gene promoter. High intake of vegetables and low intake of potato were associated with increased likelihood of gastric cancer with hypermethylation of the hMLH1 gene promoter. Genetic polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1,ALDH2, and L-mycgenes were not significantly associated with the risk of gastric cancer either with or without hypermethylation in the promoter of the hMLH1 gene.Hypermethylation of the hMLH1 promoter was significantly associated with microsatellite instability (MSI): 10 of the 14 (71.4%) MSI-positive tumors showed hypermethylation,whereas 28 of 94 (29.8%) the MSI-negative tumors were hypermethylated at the hMLH1 promoter region.Hypermethylation of the hMLH1 gene promoter was significantly inversely correlated with mutation of the p53gene.CONCLUSION: These results suggest that cigarette smoking and alcohol consumption may influence the development of hMLH1-positive gastric cancer. Most dietary factors and polymorphisms of GSTM1, GSTT1,CYP1A1, CYP2E1, ALDH2, and L-myc genes are not independent risk factors for gastric cancer with hypermethylation of the hMLH1 promoter. These data also suggest that there could be two or more different molecular pathways in the development of gastric cancer, perhaps involving tumor suppression mechanisms or DNA mismatch repair.
基金National Natural Science Foundation of China,№48970193
文摘INTRODUCTIONChina is a country with a high incidence of liver cancer insome areas.Liver cancer has a wide distribution andthreatens human health seriously.A rough estimationshows that out of a population of 1.2×10~8 in liver
基金supported by the MOSTI Science Funding Project(No. 5450100)
文摘The concentration of carcinogenic polycyclic aromatic hydrocarbons （c-PAHs） present in the sediment and water of Peninsular Malaysia as well as in the cockle Anadara granosa was investigated. Samples were extracted and analysed with gas chromatographymass spectrometry. The concentrations of total carcinogenic polycyclic aromatic hydrocarbons （t-PAHs） were measured between 0.80±0.04 to 162.96 ±14.74 ng/g wet weight （ww） in sediment, between 21.85± 2.18 to 76.2± 10.82 ng/L in water samples and between 3.34 ±0.77 to 46.85 ± 5.50 ng/g ww in the cockle tissue. The risk assessment of probable human carcinogens in the Group B2 PAHs was calculated and assessed in accordance with the standards of the United States Environmental Protection Agency （US EPA）. Case I in the toxicity assessment analysed the cancer risk to consumers of Malaysian blood cockle. Case II assessed the risk of cancer from exposure to PAHs from multiple pathways. The average cancer risk of case I and case II were found to be classifiable as unsafe according to the US EPA standard. The cancer risk due to c-PAHs acquired by the ingestion of blood cockle was （8.82 ± 0.54） × 10^ 6 to （2.67 ± 0.06） × 10^-2, higher than the US EPA risk management criterion. The non-cancer risks associated with multiple pathways in Kuala Gula, Kuala Juru and Kuala Perlis were higher than the US EPA safe level, but the non-cancer risk for eating blood cockle was below the level of US EPA concern.
文摘Helicobacter pylori (H. pylori) is a gram negative microaerophilic bacterium which resides in the mucous linings of the stomach. It has been implicated in the causation of various gastric disorders including gastric cancer. The geographical distribution and etiology of gastric cancer differ widely in different geographical regions and H. pylori, despite being labeled as a grade I carcinogen, has not been found to be associated with gastric cancer in many areas. Studies in Asian countries such as Thailand, India, Bangladesh, Pakistan, Iran, Saudi Arabian countries, Israel and Malaysia, have reported a high frequency of H. pylori infection co-existing with a low incidence of gastric cancer. In India, a difference in the prevalence of H. pylori infection and gastric cancer has been noted even in different regions of the country leading to a puzzle when attempting to find the causes of these variations. This puzzle of H. pylori distribution and gastric cancer epidemiology is known as the Indian enigma. In this review we have attempted to explain the Indian enigma using evidence from various Indian studies and from around the globe. This review covers aspects of epidemiology, the various biological strains present in different parts of the country and within individuals, the status of different H. pylori-related diseases and the molecular pathogenesis of the bacterium.
基金Supported by funding (100%) from the Department of Science and Technology, New Delhi through the Fast Track Young Scientist Project Award to Dr. Imtiyaz Murtaza, No. SR/FTP/LS-A-91/2001
文摘AIM： To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma （ESCC） among the Kashmiri population of Northern India. METHODS： All cases （n = 51） and controls （n = 150） were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases （n = 45） and inpatient controls （n = 150） with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient＇s age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls.RESULTS： Thirty-five of 45 （77.8%） histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed gerrnline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 （77.7%）, that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance （P 〈 0.05） with familial history of cancer （CD = 58）, suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable ＂Hakh＂ （CD = 19.5）, red chillies （CD = 20.2）, hot salty soda tea （CD = 2.37） and local baked bread （CD = 1.1）. CONCLUSION： Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and ＂Hakh＂, that are rich in nitrosoamines and familial cancer history.
基金the Division of Research Promotion,Ubon Rajthanee UniversityDivision of Research, College of MedicinePublic Health, Ubon Rajthanee University
文摘Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas.
基金supported by the "Laboratory Capacity Building Project" of Shenzhen Municipal Science and Technology Innovation Council, China (No. ZDSY20120614145024623)the State Key Program of National Natural Science of China (No. 41230634)
文摘Urbanization may cause increased exposure levels to polycyclic aromatic hydrocarbons （PAHs） and associated health risks for over half of the world＇s population living in cities, but little evidence has shown a direct spatial relationship between urbanization and soil PAH pollution. Based on the monitored PAH concentrations in 188 topsoil （0-5 cm） samples in Shenzhen, the most rapidly developing city in China, in recent decades, we applied geographical demarcation to determine the occurrences, source apportionments, and spatial ecological risks of soil PAHs across five zones of varying urban densities. Mean concentrations of the 16 US Environmental Protection Agency （EPA） priority PAHs （∑16PAHs） and the 7 carcinogenic PAHs （2E7CarPAHs） both followed the order： Zone D （60%-80% constructive land density （CLD）） 〉 Zone E （80%-100% CLD） 〉 Zone C （40%-60% CLD） 〉 Zone B （20%-40% CLD） 〉 Zone A （0%-20% CLD）, suggesting that the highest PAH levels occurred in the suburban-urban center transitional zone （Zone D） rather than the urban center zone （Zone E） in Shenzhen. There were significant correlations of ∑16PAHs to TOC and sampling altitude across all samples but not within highly-urbanized regions （Zones D and E）, implying a considerable disturbance of urbanization to the soil PAH pool. Source apportionments suggested that soil PAHs of all zones were mainly derived from fossil fuel combustion, with Zone E showing the highest contribution from oil sources among different zones. Spatial ecological risk analysis showed that the contaminated area （467 km2; 23.9% of total area; toxic equivalency quotients 〉 33 ng g^-1） had a higher contribution from the highly-urbanized regions （Zones D and E） than the uncontaminated area （42.3% vs. 18.1%）. Overall, our study highlighted a strong spatial relationship between urbanization and soil PAH pollution.
