In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B 1 (AFB 1 ) epoxide reacts ...In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B 1 (AFB 1 ) epoxide reacts with guanine in DNA and can lead to genetic changes. In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB 1 exposure and mutations in the K -ras oncogene are related to vinyl chloride exposure. Numerous genetic alterations accumulate during the process of hepatocarcinogenesis. Chemical carcinogen DNA-adduct formation is the basis for these genetic changes and also a molecular marker which reflects exposure level and biological effects. Metabolism of chemical carcinogens, including their activation and detoxification, also plays a key role in chemical hepatocarcinogenesis. Cytochrome p450 enzymes, N -acetyltransferases and glutathione S -transferases are involved in activating and detoxifying chemical carcinogens. These enzymes are polymorphic and genetic variation influences biological response to chemical carcinogens. This genetic variation has been postulated to influence the variability in risk for HCC observed both within and across populations. Ongoing studies seek to fully understand the mechanisms by which genetic variation in response to chemical carcinogens impacts on HCC risk.展开更多
In this paper our studies about the sequential testing program for predicting and identificating carcinogens, sequential discriminant method and cost- effectiveness analysis are summarized. The analysis of our databas...In this paper our studies about the sequential testing program for predicting and identificating carcinogens, sequential discriminant method and cost- effectiveness analysis are summarized. The analysis of our database of carcinogeniclty and genotoxicity of chemicals demonstrates the uncertainty . of short- term tests ( STTs ) to predict carcinogens and the results of most routine STTs are statistically dependent. We recommend the sequential testing program combining STTs and carclnogenicity assay, the optimal STT batteries, the rules of the sequential discrimination and the preferal choices of STTs tor specific chemical class. For illustrative pmposes the carclnogenicity prediction of several sample chamicals is presented. The results of cost-effectiveness analysis suggest that this program has vast social-economic effectiveness.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
Environmental, occupational, or dietary exposure to certain chemicals has been shown to be associated with carcinogenesis in humans. In the 18th century, for example, Percival Pott (1775) noted a high incidence of scr...Environmental, occupational, or dietary exposure to certain chemicals has been shown to be associated with carcinogenesis in humans. In the 18th century, for example, Percival Pott (1775) noted a high incidence of scrotal cancer in chimney sweeps, which he attributed to their exposure to soot and a concomitant lack of bathing. Subsequent epidemiological studies have identified a number of additional carcinogenic agents, including aromatic amine-based dyes (Case et al., 1954), cigarette smoke (Wynder and Graham, 1950), asbestos (Doll, 1955), vinyl chloride (Creech and展开更多
The no-observed-effect level (NOEL) in a study of carcinogenicity for compounds that are both genotoxic and carcinogenic represents the limit of detection in that bioassay, rather than an estimate of a possible thresh...The no-observed-effect level (NOEL) in a study of carcinogenicity for compounds that are both genotoxic and carcinogenic represents the limit of detection in that bioassay, rather than an estimate of a possible threshold. Therefore, for those genotoxic and carcinogenic contaminants (e.g. acrylamides, PAHs, etc.) in foods it is not possible to develop health-based guidance values (e.g. ADI or PTWI) using the traditional NOEL and safety/uncertainty factors.展开更多
The decision to classify a chemical as a human carcinogen must depend upon agreed conclusions from epidemiology, bioassays, and some short-term corroborating tests; information from only one of these disciplines is in...The decision to classify a chemical as a human carcinogen must depend upon agreed conclusions from epidemiology, bioassays, and some short-term corroborating tests; information from only one of these disciplines is inadequate. Most pitfalls appear in interpreting the results from animal bioassays; this report will concentrate on them. Often the conclusion is accepted that a chemical is an animal carcinogen without a critical appraisal of the experimental design. By manipulating the experiment, 90 + % of all chemicals can induce some tumor in a rodent. Pitfalls encountered in bioassays result from not specifying the exact agent under test and how it relates to human exposure, using inappropriate routes of administration unrelated to humans, administering illogically high doses, or concluding that a cancer was induced without adequate histopathological description of the lesion. Importance of animal husbandry is often overlooked. Pitfalls are also related to short-term tests. Finally, a major pitfall in assessing carcinogenic risk from chemicals is drawing global conclusions about the carcinogenicity of an agent after the detection of only one or two tumors in the treated group.展开更多
Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment. In turn, chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechani...Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment. In turn, chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechanisms. There were described in literature several simple, rapid and inexpensive short term tests to reasonably predict the genotoxic nature of chemicals but in contrast, there is no reliable test or battery of tests available to predict the carcinogenicity of non-genotoxic compounds and this poses a major problem to their risk assessment. In addition, there are conflictive opinions about risk assessment needs for both classes of carcinogens. Some workers believe that for non-genotoxic carcinogens, thresholds for exposure can be drawn while others do not. In this review, the reasons behind both of these opinions and the present hypotheses about the mechanism of action of non-genotoxic carcinogens are described and analyzed in relation to future needs.展开更多
Exposure to cigarette smoke is a major risk factor for cancer and cardiovascular disease. Thrombosis is regarded as the main reason for smoking-related car- diovascular disease. However, the detail mechanism of how sm...Exposure to cigarette smoke is a major risk factor for cancer and cardiovascular disease. Thrombosis is regarded as the main reason for smoking-related car- diovascular disease. However, the detail mechanism of how smoking promotes thrombosis is not fully under- stood. In this work, we investigated the impacts of one major cigarette carcinogens 4-（methylnitrosamino）-l-（3- pyridyl）-l-butanone （NNK） as well as its metabolite 4-（methylnitrosamino）- 1-（3-pyridyl）- 1-butanol （NNAL） on a key process in thrombosis regulation： thrombin- thrombomodulin （TM） binding. Atomic force microscopy based single-molecule force spectroscopy was applied to measure both in vitro and in vivo binding force of thrombin to TM in the absence and presence of NNK and NNAL respectively. The results revealed that NNK and NNAL can reduce the binding probability of TM and thrombin. The inhibition effect and underlying mechanism was further studied by molecular simulation. As indicated by our results, the cigarette carcinogens could cause a higher risk of thrombosis through the disruption of TM- thrombin interaction.展开更多
Recently, Ng et al. reported that the A：T 〉 T：A substitutions, proposed to be a signature of aristolochic acid （AA） exposure, were detected in 76/98 （78%） of patients with hepatocellular carcinoma （HCC） from ...Recently, Ng et al. reported that the A：T 〉 T：A substitutions, proposed to be a signature of aristolochic acid （AA） exposure, were detected in 76/98 （78%） of patients with hepatocellular carcinoma （HCC） from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients＇ exposure history is the key to determine the ＂culprit＂ of the A：T 〉 T：A mutations. Apparently, without estimation of the patients＇ exposure history, the conclusion of Ng et al, is unpersuasive and misleading.展开更多
To investigate the presence of metal elements and assess their health risk for the populace in the Nandong Underground River Basin(NURB),we conducted an analysis of eleven common heavy metals in the water body.A Healt...To investigate the presence of metal elements and assess their health risk for the populace in the Nandong Underground River Basin(NURB),we conducted an analysis of eleven common heavy metals in the water body.A Health risk assessment(HRA)model was employed to analyze 84 water samples from the NURB.The detection results revealed the following order of heavy metals concentrations:Fe>Al>Mn>Zn>As>Cd>Pb>Cr>Ni>Cu>Hg.Correlation analysis indicated a certain similarity in material source and migration transformation among these eleven metal elements.Our study identified that the health risks for local residents exposed to metal elements in the water of NURB primarily stem from carcinogenic risk(10^(−6)–10^(−4)a^(−1))through the drinking water pathway.Moreover,the health risk of heavy metal exposure for children through drinking water was notably higher than for adults.The maximum health risks of Cr in both underground and surface water exceeded the recommendation standard(5.0×10^(−5)a^(−1))from ICRP,surpassing the values recommended by the Swedish Environmental Protection Agency,the Dutch Ministry of Construction and Environment and the British Royal Society(5.0×10^(−6)a^(−1)).The results of the health risk assessment indicate that Cr in the water of NURB is the primary source of carcinogenic risk for local residents,followed by Cd and As.Consequently,it is imperative to control these three carcinogenic metals when the water was used as drinking water resource.展开更多
The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates...The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.展开更多
BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is...BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.展开更多
To understand the levels of potentially toxic elements(PTEs)contamination in soils and their effects on human health from different agricultural land use in Sanya,China.128 soil samples(64 topsoil samples and correspo...To understand the levels of potentially toxic elements(PTEs)contamination in soils and their effects on human health from different agricultural land use in Sanya,China.128 soil samples(64 topsoil samples and corresponding subsoil samples)were collected from the five representative land-use patterns.Inductively coupled plasma mass spectrometry(ICP-MS),Atomic fluorescence spectrometry(AFS),and Inductively coupled plasma optical emission spectrometry(ICP-OES)were used to determine the content of PTEs(As,Cd,Hg,Cu,Cr,Ni,Pb,Zn,Co,Mo,Sb,and V).Correlation analysis and factor analysis were used to determine the source of PTEs.Geo-accumulation index(I_(geo)),hazard quotient(HQ),and total carcinogenic risk index(TR)were used to measure the PTEs contamination and its relative health impacts.Results showed that the average values of 12 PTEs in topsoil were higher than the Hainan soil geochemical baseline,showing different degrees of PTEs accumulation effect.The concentration of PTEs in the topsoil was lower than those in the subsoil except for Cd and Hg.The I_(geo)revealed that the major accumulated element in soils was As followed by Mo.Source apportionment suggested that parent materials and agricultural practices were the dominant factors for PTEs accumulation in the topsoil.Noncarcinogenic risks of soil samples from five land-use patterns presented a trend of paddy field>dry field>woodland>orchard>garden plot.However,the HQ values of 12 PTEs were less than the recommended limit of HQ=1,representing that there are no non-carcinogenic risks of PTEs for children and adults in the study area.The TR values are within 6.95×10^(-6)-1.38×10^(-5),which corresponds to the low level.Therefore the PTEs in the agricultural soil of the study area show little influence on the health status of the local population.展开更多
Unani medicine is an oldest system of traditional medicine,where drugs of animal,mineral and herbal origin are used for centuries to cure diseases.Unani remedies are now available not only in drug stores,but also in f...Unani medicine is an oldest system of traditional medicine,where drugs of animal,mineral and herbal origin are used for centuries to cure diseases.Unani remedies are now available not only in drug stores,but also in food stores and super markets.Therefore the efficacy and safety of these drugs is very crucial.One of the most serious risks associated with these remedies is,consumer assumes that they are natural,so they are safe.But biological contamination(bacterial,fungal and insect)of herbal medicines is a serious concern.The Aspergillus flavus and Aspergillus parasiticus are the fungal species that occur naturally,release aflatoxins and is a threat to the natural drugs.The World Health Organization has recommended determination of aflatoxins in natural drugs(Unani)as one of the parameter of their safety studies as Aflatoxin contamination is concerned significantly with health and economic loss affecting humans,animals,and agriculture.Aflatoxin B1 is categorized as a group 1 carcinogen by The International Agency for Research on Cancer that causes a variety of health issues.Thus keeping in mind the deleterious health effects of aflatoxins,here,in this review we have made an attempt to summarize the aflatoxins with respect to their origin,occurrence,structure and properties to generate the awareness among the people dealing mainly with Unani herbal drugs.Besides these their toxicity and effects on health have also been discussed.The analytical methods for their determination and some measures to prevent their contamination are also suggested to improve the efficacy and safety of Unani herbal drugs.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
Trail, a tumor necrosis factor-related apoptosis-inducing ligand, is a novel potent endogenous activator of the cell death pathway through the activation of cell surface death receptors Trail-R1 and Trail-R2. Its role...Trail, a tumor necrosis factor-related apoptosis-inducing ligand, is a novel potent endogenous activator of the cell death pathway through the activation of cell surface death receptors Trail-R1 and Trail-R2. Its role, like FasL in activation-induced cell death (AICD), has been demonstrated in immune system. However the mechanism of Trail induced apoptosis remains unclear. In this report, the recombinant Trail protein was expressed and purified. The apoptosis-inducing activity and the regulation mechanism of recombinant Trail on Jurkat T cells were explored in vitro. Trypan blue exclusion assay demonstrated that the recombinant Trail protein actively killed Jurkat T cells in a dose-dependent manner. Trail-induced apoptosis in Jurkat T cells were remarkably reduced by Bcl-2 over expression in Bcl-2 gene transfected cells. Treatment with PMA (phorbol 12-myristate 13-acetate), a PKC activator, suppressed Trail-induced apoptosis in Jurkat T cells. The inhibition of apoptosis by PMA was abolished by pretreatment with Bis, a PKC inhibitor. Taken together, it was suggested that Bcl-2 over-expression and PMA activated PKC actively down-regulated the Trail-mediated apoptosis in Jurkat T cell.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
文摘In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B 1 (AFB 1 ) epoxide reacts with guanine in DNA and can lead to genetic changes. In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB 1 exposure and mutations in the K -ras oncogene are related to vinyl chloride exposure. Numerous genetic alterations accumulate during the process of hepatocarcinogenesis. Chemical carcinogen DNA-adduct formation is the basis for these genetic changes and also a molecular marker which reflects exposure level and biological effects. Metabolism of chemical carcinogens, including their activation and detoxification, also plays a key role in chemical hepatocarcinogenesis. Cytochrome p450 enzymes, N -acetyltransferases and glutathione S -transferases are involved in activating and detoxifying chemical carcinogens. These enzymes are polymorphic and genetic variation influences biological response to chemical carcinogens. This genetic variation has been postulated to influence the variability in risk for HCC observed both within and across populations. Ongoing studies seek to fully understand the mechanisms by which genetic variation in response to chemical carcinogens impacts on HCC risk.
文摘In this paper our studies about the sequential testing program for predicting and identificating carcinogens, sequential discriminant method and cost- effectiveness analysis are summarized. The analysis of our database of carcinogeniclty and genotoxicity of chemicals demonstrates the uncertainty . of short- term tests ( STTs ) to predict carcinogens and the results of most routine STTs are statistically dependent. We recommend the sequential testing program combining STTs and carclnogenicity assay, the optimal STT batteries, the rules of the sequential discrimination and the preferal choices of STTs tor specific chemical class. For illustrative pmposes the carclnogenicity prediction of several sample chamicals is presented. The results of cost-effectiveness analysis suggest that this program has vast social-economic effectiveness.
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Environmental, occupational, or dietary exposure to certain chemicals has been shown to be associated with carcinogenesis in humans. In the 18th century, for example, Percival Pott (1775) noted a high incidence of scrotal cancer in chimney sweeps, which he attributed to their exposure to soot and a concomitant lack of bathing. Subsequent epidemiological studies have identified a number of additional carcinogenic agents, including aromatic amine-based dyes (Case et al., 1954), cigarette smoke (Wynder and Graham, 1950), asbestos (Doll, 1955), vinyl chloride (Creech and
文摘The no-observed-effect level (NOEL) in a study of carcinogenicity for compounds that are both genotoxic and carcinogenic represents the limit of detection in that bioassay, rather than an estimate of a possible threshold. Therefore, for those genotoxic and carcinogenic contaminants (e.g. acrylamides, PAHs, etc.) in foods it is not possible to develop health-based guidance values (e.g. ADI or PTWI) using the traditional NOEL and safety/uncertainty factors.
文摘The decision to classify a chemical as a human carcinogen must depend upon agreed conclusions from epidemiology, bioassays, and some short-term corroborating tests; information from only one of these disciplines is inadequate. Most pitfalls appear in interpreting the results from animal bioassays; this report will concentrate on them. Often the conclusion is accepted that a chemical is an animal carcinogen without a critical appraisal of the experimental design. By manipulating the experiment, 90 + % of all chemicals can induce some tumor in a rodent. Pitfalls encountered in bioassays result from not specifying the exact agent under test and how it relates to human exposure, using inappropriate routes of administration unrelated to humans, administering illogically high doses, or concluding that a cancer was induced without adequate histopathological description of the lesion. Importance of animal husbandry is often overlooked. Pitfalls are also related to short-term tests. Finally, a major pitfall in assessing carcinogenic risk from chemicals is drawing global conclusions about the carcinogenicity of an agent after the detection of only one or two tumors in the treated group.
文摘Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment. In turn, chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechanisms. There were described in literature several simple, rapid and inexpensive short term tests to reasonably predict the genotoxic nature of chemicals but in contrast, there is no reliable test or battery of tests available to predict the carcinogenicity of non-genotoxic compounds and this poses a major problem to their risk assessment. In addition, there are conflictive opinions about risk assessment needs for both classes of carcinogens. Some workers believe that for non-genotoxic carcinogens, thresholds for exposure can be drawn while others do not. In this review, the reasons behind both of these opinions and the present hypotheses about the mechanism of action of non-genotoxic carcinogens are described and analyzed in relation to future needs.
基金supported by the National Basic Research Program of China (2013CB933701, 2013CB933704)the National Natural Science Foundation of China (21127901)
文摘Exposure to cigarette smoke is a major risk factor for cancer and cardiovascular disease. Thrombosis is regarded as the main reason for smoking-related car- diovascular disease. However, the detail mechanism of how smoking promotes thrombosis is not fully under- stood. In this work, we investigated the impacts of one major cigarette carcinogens 4-（methylnitrosamino）-l-（3- pyridyl）-l-butanone （NNK） as well as its metabolite 4-（methylnitrosamino）- 1-（3-pyridyl）- 1-butanol （NNAL） on a key process in thrombosis regulation： thrombin- thrombomodulin （TM） binding. Atomic force microscopy based single-molecule force spectroscopy was applied to measure both in vitro and in vivo binding force of thrombin to TM in the absence and presence of NNK and NNAL respectively. The results revealed that NNK and NNAL can reduce the binding probability of TM and thrombin. The inhibition effect and underlying mechanism was further studied by molecular simulation. As indicated by our results, the cigarette carcinogens could cause a higher risk of thrombosis through the disruption of TM- thrombin interaction.
文摘Recently, Ng et al. reported that the A：T 〉 T：A substitutions, proposed to be a signature of aristolochic acid （AA） exposure, were detected in 76/98 （78%） of patients with hepatocellular carcinoma （HCC） from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients＇ exposure history is the key to determine the ＂culprit＂ of the A：T 〉 T：A mutations. Apparently, without estimation of the patients＇ exposure history, the conclusion of Ng et al, is unpersuasive and misleading.
基金supported from the National Key Research and Development Program of China(No.2022YFF1302901)the Key Laboratory Construction Project of Guangxi(No.19-185-7)the Foundation for Hebei Education Department(No.2022QNJS05).
文摘To investigate the presence of metal elements and assess their health risk for the populace in the Nandong Underground River Basin(NURB),we conducted an analysis of eleven common heavy metals in the water body.A Health risk assessment(HRA)model was employed to analyze 84 water samples from the NURB.The detection results revealed the following order of heavy metals concentrations:Fe>Al>Mn>Zn>As>Cd>Pb>Cr>Ni>Cu>Hg.Correlation analysis indicated a certain similarity in material source and migration transformation among these eleven metal elements.Our study identified that the health risks for local residents exposed to metal elements in the water of NURB primarily stem from carcinogenic risk(10^(−6)–10^(−4)a^(−1))through the drinking water pathway.Moreover,the health risk of heavy metal exposure for children through drinking water was notably higher than for adults.The maximum health risks of Cr in both underground and surface water exceeded the recommendation standard(5.0×10^(−5)a^(−1))from ICRP,surpassing the values recommended by the Swedish Environmental Protection Agency,the Dutch Ministry of Construction and Environment and the British Royal Society(5.0×10^(−6)a^(−1)).The results of the health risk assessment indicate that Cr in the water of NURB is the primary source of carcinogenic risk for local residents,followed by Cd and As.Consequently,it is imperative to control these three carcinogenic metals when the water was used as drinking water resource.
文摘The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.
文摘BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.
基金supported by Open Foundation of the Key Laboratory of Coupling Process and Effect of Natural Resources Elements(No.2023KFKTB001)the Science&Technology Fundamental Resources Investigation Program(2022FY101800)+2 种基金the National Nonprofit Institute Research Grant of IGGE(AS2023D01)the projects of the China Geological Survey(DD20230309 and DD20190305)the National Natural Science Foundation of China(42002105)。
文摘To understand the levels of potentially toxic elements(PTEs)contamination in soils and their effects on human health from different agricultural land use in Sanya,China.128 soil samples(64 topsoil samples and corresponding subsoil samples)were collected from the five representative land-use patterns.Inductively coupled plasma mass spectrometry(ICP-MS),Atomic fluorescence spectrometry(AFS),and Inductively coupled plasma optical emission spectrometry(ICP-OES)were used to determine the content of PTEs(As,Cd,Hg,Cu,Cr,Ni,Pb,Zn,Co,Mo,Sb,and V).Correlation analysis and factor analysis were used to determine the source of PTEs.Geo-accumulation index(I_(geo)),hazard quotient(HQ),and total carcinogenic risk index(TR)were used to measure the PTEs contamination and its relative health impacts.Results showed that the average values of 12 PTEs in topsoil were higher than the Hainan soil geochemical baseline,showing different degrees of PTEs accumulation effect.The concentration of PTEs in the topsoil was lower than those in the subsoil except for Cd and Hg.The I_(geo)revealed that the major accumulated element in soils was As followed by Mo.Source apportionment suggested that parent materials and agricultural practices were the dominant factors for PTEs accumulation in the topsoil.Noncarcinogenic risks of soil samples from five land-use patterns presented a trend of paddy field>dry field>woodland>orchard>garden plot.However,the HQ values of 12 PTEs were less than the recommended limit of HQ=1,representing that there are no non-carcinogenic risks of PTEs for children and adults in the study area.The TR values are within 6.95×10^(-6)-1.38×10^(-5),which corresponds to the low level.Therefore the PTEs in the agricultural soil of the study area show little influence on the health status of the local population.
文摘Unani medicine is an oldest system of traditional medicine,where drugs of animal,mineral and herbal origin are used for centuries to cure diseases.Unani remedies are now available not only in drug stores,but also in food stores and super markets.Therefore the efficacy and safety of these drugs is very crucial.One of the most serious risks associated with these remedies is,consumer assumes that they are natural,so they are safe.But biological contamination(bacterial,fungal and insect)of herbal medicines is a serious concern.The Aspergillus flavus and Aspergillus parasiticus are the fungal species that occur naturally,release aflatoxins and is a threat to the natural drugs.The World Health Organization has recommended determination of aflatoxins in natural drugs(Unani)as one of the parameter of their safety studies as Aflatoxin contamination is concerned significantly with health and economic loss affecting humans,animals,and agriculture.Aflatoxin B1 is categorized as a group 1 carcinogen by The International Agency for Research on Cancer that causes a variety of health issues.Thus keeping in mind the deleterious health effects of aflatoxins,here,in this review we have made an attempt to summarize the aflatoxins with respect to their origin,occurrence,structure and properties to generate the awareness among the people dealing mainly with Unani herbal drugs.Besides these their toxicity and effects on health have also been discussed.The analytical methods for their determination and some measures to prevent their contamination are also suggested to improve the efficacy and safety of Unani herbal drugs.
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Major State BasicResearch (973) Program of China, (G1999053905).
文摘Trail, a tumor necrosis factor-related apoptosis-inducing ligand, is a novel potent endogenous activator of the cell death pathway through the activation of cell surface death receptors Trail-R1 and Trail-R2. Its role, like FasL in activation-induced cell death (AICD), has been demonstrated in immune system. However the mechanism of Trail induced apoptosis remains unclear. In this report, the recombinant Trail protein was expressed and purified. The apoptosis-inducing activity and the regulation mechanism of recombinant Trail on Jurkat T cells were explored in vitro. Trypan blue exclusion assay demonstrated that the recombinant Trail protein actively killed Jurkat T cells in a dose-dependent manner. Trail-induced apoptosis in Jurkat T cells were remarkably reduced by Bcl-2 over expression in Bcl-2 gene transfected cells. Treatment with PMA (phorbol 12-myristate 13-acetate), a PKC activator, suppressed Trail-induced apoptosis in Jurkat T cells. The inhibition of apoptosis by PMA was abolished by pretreatment with Bis, a PKC inhibitor. Taken together, it was suggested that Bcl-2 over-expression and PMA activated PKC actively down-regulated the Trail-mediated apoptosis in Jurkat T cell.
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.
