ABSTRACT
This study investigated the source and contamination levels of toxic elements (Cd, Cr, As, Pb, Ni and Hg) present in a coastal environment, Paradip-an industrial hub of the east coast of India. The ecological risk assessment indices and human exposure models were used to evaluate the pollution status. Enrichment factor indicated that all the metal(loid)s found in the sediment are mostly derived from the anthropogenic source. According to the sediment quality quotient, 8.33% of sediments have crossed the ERM limit for Ni that can be fatal to biota. Meanwhile, 66.66, 41.66 and 8.33% of sediments have exceeded PEL range for Cr, Ni and As, respectively, that can register frequent lethal toxicity to benthic biota. As had the highest potential ecological harm coefficient (Erf > 80), and Hg had moderate ecological harm coefficient (40 < Erf < 80). Summarily, the sediment quality of this site is moderate to heavily toxic to benthic organisms. The concentration of toxic metals in seawater was below the permissible limit (CCC and CMC) set by USEPA indicating that water is relatively safer for free floating aquatic biota. The health risk index of toxic metal (loid)s present in soils of the residential sites has confirmed that there is a severe non-carcinogenic threat for children (HI child > 1) and a borderline carcinogenic risk for both adult and children. THQCr possesses highest non-carcinogenic threat, which contributed approximately 50% to HI followed by THQAs. The contribution of carcinogenic risk of chromium (CRCr) to TCR is approximately 60%. Cr is the significant contaminant of this site that has highest health effects. Highest exposure risks were associated with ingestion pathway accounting for about 85% of the total for most of the elements.
Subject(s)
Arsenic/analysis , Environmental Monitoring , Metals, Heavy/analysis , Soil Pollutants/analysis , Water Pollutants, Chemical/analysis , Geologic Sediments/analysis , Humans , Industrial Waste/analysis , Risk Assessment , Seawater/analysisABSTRACT
The research depicts the spatial and temporal variation of major and trace metals in marine sediments at various monitoring stations of Dhamra estuary, Bay of Bengal, Odisha. The concentration and distribution of selected metals in surface sediments of the estuary were studied in order to assess the spatial extent of anthropogenic inputs viz., mining activities and to estimate the effects of seasonal variations on geochemical processes in this particular tropical estuarine system. Surface sediments reflect the presence of trace and major metals in parts per million, and the concentrations vary in the range of Cu (0.083 to 127.2), Ni (17.35 to 122.8), Co (1.2 to 31.58), Pb (0.8 to 95.86), Zn (12.1 to 415), Cd (0 to 11) and Cr (35.21 to 5,890), Fe (7,490 and 169,100), Mn (20 to 69,188), Ca (10 to 10,520), Mg (990 to 28,750), Na (300 to 51,700), and K (1,100 to 30,010). The comparison of spatial distribution of metal contents using GIS in marine sediments indicates that there is a substantial anthropogenic input in the Dhamra estuary. The enrichment of Cr is ascribed to the sedimentation of Brahmani River, passing through the mining region and discharging Cr pollutant to the sea. Similarly, the sources of Cd are attributable to corrosion-resistant paints used by a large number of trawlers. Contamination factor has been calculated for various metals to assess the degree of pollution. As per Hakanson's classification, Cr indicates very high contamination with considerable contamination of Cd, whereas moderate contamination of Pb, Zn, and Mn are observed in marine sediments. Pollution load index also indicate that there is deterioration of site quality in premonsoon season, which almost attains the baseline level in post monsoon and perfection in monsoon season (Tomlinson et al. (Helgolander Wissenschaftliche Meeresuntersuchungen, 33, 566-572, 1980)). The geoaccumulation index shows that the metal concentrations in sediments can be considered as background levels except Cr and Cd. The geoaccumulation index shows that Cr is moderately contaminated and it is higher in offshore region in post monsoon and monsoon than premonsoon season. All the calculated indices show that Cr and Cd levels are more than the desired limits in the marine sediments. Multivariate statistical analysis evaluates the plausible sources of contaminants, attributing to mining, industrial, and urban wastes by way of Brahmani River discharging to the estuarine region.
Subject(s)
Environmental Monitoring , Geologic Sediments/chemistry , Metals/analysis , Water Pollutants, Chemical/analysis , Bays/chemistry , Estuaries , India , Multivariate Analysis , Oceans and Seas , Seasons , Spatio-Temporal AnalysisABSTRACT
Petroleum hydrocarbon (PHC) concentration was monitored in water of estuaries, ports, and coastal transects up to 10-km distance in East Coast of India once in every year during 2002-2009. The highest concentration was observed at Haldia port (1.60-20.11 µg/l) due to the impact of hydrocarbon discharges from nearby oil refinery, petrochemical industries, handling of crude oils, etc. The concentration of PHC exhibited relatively higher values during low tide than the high tide in all the four estuaries indicating riverine inputs and land-based discharges, which contribute substantial amounts of PHC to the coastal water. Hoogly estuary recorded higher values of PHC (1.17-18.50 µg/l) due to the influence of industrial wastes, land runoff, and port activities. The spatial distribution of PHC estimated by the kriging method showed a variation in concentration of PHC over the whole region. To discriminate the dispersion pattern of PHC, principal component analysis (PCA) was performed using a correlation matrix.
Subject(s)
Environmental Monitoring/methods , Hydrocarbons/analysis , Petroleum/analysis , Water Pollutants, Chemical/analysis , Bays/chemistry , India , Industrial Waste/analysis , Spatial Analysis , Spatio-Temporal Analysis , Water Pollution, Chemical/statistics & numerical dataABSTRACT
The Standard Model of particle physics is known to be incomplete. Extensions to the Standard Model, such as weak-scale supersymmetry, posit the existence of new particles and interactions that are asymmetric under time reversal (T) and nearly always predict a small yet potentially measurable electron electric dipole moment (EDM), d(e), in the range of 10(-27) to 10(-30) e·cm. The EDM is an asymmetric charge distribution along the electron spin (S(â)) that is also asymmetric under T. Using the polar molecule thorium monoxide, we measured d(e) = (-2.1 ± 3.7stat ± 2.5syst) × 10(-29) e·cm. This corresponds to an upper limit of |d(e)| < 8.7 × 10(-29) e·cm with 90% confidence, an order of magnitude improvement in sensitivity relative to the previous best limit. Our result constrains T-violating physics at the TeV energy scale.
ABSTRACT
The chemistry of heavy metals in sediments with respect to bio-availability and chemical reactivity is regulated by pH, texture, and organic matter contents of the sediments and specific binding form and coupled reactivity of the metals within. To focus on the metal distribution (Fe, Mn, Pb, Cd, Zn, Co, Cu, and Cr) and behavior in a fresh water aquifer system along with the ecological toxicity parameters, a four-step sequential extraction method was applied on 18 Eastern Ghats' type sediments from fluorosis-hit Nayagarh district, India. Geo-accumulation index of metals in the sediments indicates that they are practically uncontaminated and/or less contaminated with and Fe, Mn, and Cu; contaminated to moderately contaminated with Pb, Zn, and Cr; and strongly contaminated with Cd. Rather, more than 80 % recovered Cd metal concentration in sediments constitute the labile fractions. Temporal clustering of metal fractions indicates transition metal fraction distribution claiming the sediment pH regulation. Similarly, base metal distribution accounts for organic carbon and soil conductivity due to their greater availability in exchangeable and sulfide fractions. Correlation analysis and factor analysis scores demonstrate lack of inter-relationship between transition group and base metal fractions. High fluoride concentration in ground water is associated with high sodium-bicarbonate-iron affinity with elevated pH values (i.e., >7.0) and high positive factor score with the total iron concentration in ground water.
Subject(s)
Environmental Monitoring , Groundwater/chemistry , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , Fresh Water/chemistry , Geologic Sediments/chemistry , India , Metals, Heavy/toxicity , Risk Assessment , Soil Pollutants/analysis , Water Pollutants, Chemical/toxicity , Water Pollution, Chemical/statistics & numerical dataABSTRACT
The spindle assembly checkpoint (SAC) is a 'wait-anaphase' mechanism that has evolved in eukaryotic cells in response to the stochastic nature of chromosome-spindle attachments. In the recent past, different aspects of the SAC regulation have been described. However, the role of microRNAs in the SAC is vaguely understood. We report here that Mad1, a core SAC protein, is repressed by human miR-125b. Mad1 serves as an adaptor protein for Mad2 - which functions to inhibit anaphase entry till the chromosomal defects in metaphase are corrected. We show that exogenous expression of miR-125b, through downregulation of Mad1, delays cells at metaphase. As a result of this delay, cells proceed towards apoptotic death, which follows from elevated chromosomal abnormalities upon ectopic expression of miR-125b. Moreover, expressions of Mad1 and miR-125b are inversely correlated in a variety of cancer cell lines, as well as in primary head and neck tumour tissues. We conclude that increased expression of miR-125b inhibits cell proliferation by suppressing Mad1 and activating the SAC transiently. We hypothesize an optimum Mad1 level and thus, a properly scheduled SAC is maintained partly by miR-125b.
Subject(s)
Apoptosis , Cell Cycle Proteins/metabolism , MicroRNAs/metabolism , Mitosis , Nuclear Proteins/metabolism , 3' Untranslated Regions , Anaphase , Base Sequence , Calcium-Binding Proteins/metabolism , Cell Cycle Proteins/antagonists & inhibitors , Cell Cycle Proteins/genetics , Cell Line, Tumor , Cell Proliferation , Chromosome Aberrations , Down-Regulation , HCT116 Cells , Hep G2 Cells , Humans , M Phase Cell Cycle Checkpoints , Mad2 Proteins , MicroRNAs/genetics , Nuclear Proteins/antagonists & inhibitors , Nuclear Proteins/genetics , Repressor Proteins/metabolismABSTRACT
BACKGROUND: Alteration of chromosome 9q22.3 region is an early and frequent event in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to understand the association of candidate tumor suppressor genes PHF2, FANCC, PTCH1, and XPA located in this region in the development of HNSCC. METHODS: The alterations (deletion, promoter methylation, mutation, expression) of these genes were analyzed in 65 dysplastic head and neck lesions and 84 primary HNSCC samples. Clinicopathologic correlations were made with alterations of the genes. RESULTS: Overall alterations (deletion, promoter methylation) of FANCC and PTCH1 were high in mild dysplasia and comparable in subsequent stages of tumor progression. However, PHF2 alteration was low in mild dysplasia, but increased in moderate and severe dysplasias. Alterations (deletion, promoter methylation) of FANCC and PTCH1 showed association with each other. Two novel mutations in GLI binding sites of PTCH1 promoter and a novel microsatellite marker hmPTCH1 with four alleles at immediate upstream of the gene were identified. In a case-control study, the (CGG)7 allele of hmPTCH1 was found to be susceptible for HNSCC development. Concordance was seen in the expression (RNA, protein) of these genes with their molecular alterations. CONCLUSIONS: Alterations of FANCC and PTCH1 could be used as molecular marker for early diagnosis and prognosis of HNSCC.
Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Transformation, Neoplastic/genetics , Fanconi Anemia Complementation Group C Protein/genetics , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Receptors, Cell Surface/genetics , Adult , Aged , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/virology , Case-Control Studies , Cell Line, Tumor , Chromosomes, Human, Pair 9 , Confidence Intervals , DNA, Viral/isolation & purification , Female , Gene Expression , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/virology , Homeodomain Proteins/genetics , Human papillomavirus 16 , Human papillomavirus 18 , Humans , Male , Methylation , Middle Aged , Odds Ratio , Patched Receptors , Patched-1 Receptor , Promoter Regions, Genetic , RNA, Messenger , Sequence Deletion , Xeroderma Pigmentosum Group A Protein/genetics , Young AdultABSTRACT
BRCA1 gene expression in familial breast cancer is mainly focused on mutational analysis. However in sporadic cancers BRCA1 protein expression is the main area of interest because somatic inactivation of one allele of the gene is likely to occur during the oestrogen mediated proliferation at puberty and subsequent tumourigenic events take place in the same cell. Standard immunohistochemical analysis was used to assess BRCA1 and oestrogen/progesterone receptor (ER/PR) status in familial and sporadic breast cancer patients and correlation of BRCA1 protein expression with histopathological features ER/PR status was studied in these tumours. One hundred and seventy-seven sporadic tumours (group A) and 28 familial tumours (patients with history of breast cancer in first or second degree relative ie, group B) were studied. In group A, 61 tumours had absent/reduced BRCA 1 protein expression; 30 (49%) out of these were negative for ER/PR receptors. In group B, 18 patients had absent/reduced BRCA1 protein expression, and 10 (55.6%) out of these, were ER/PR negative. Overall in 2 groups, 82 tumours were of grade 1, 61 tumours of grade 2 and 62 tumours were of grade 3 differentiation. Test of proportion showed that percentage of ER/PR negativity is significantly higher than ER/PR positivity in sporadic as well as in familial tumours with absent/ reduced BRCA 1 protein expression (p < 0.05). Sporadic tumours with deranged BRCA1 protein expression like familial tumours have more unfavourable histopathological characteristics and are likely to be of higher grade and oestrogen receptor negative
Subject(s)
BRCA1 Protein/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma/metabolism , Carcinoma/pathology , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Adult , Breast Neoplasms/genetics , Carcinoma/genetics , Female , Gene Expression , Humans , India , Male , Middle Aged , Neoplasm Grading , Prospective Studies , Young AdultABSTRACT
A simple, specific, accurate and stability-indicating UV- Spectrophotometric method was developed for the estimation of candesartan cilexitil, using a Shimadzu, model 1700 spectrophotometer and a mobile phase composed of methanol: water in the ratio of 9:1 at wave length (λ(max)) 254 nm. Linearity was established for candesartan in the range of 10-90 µg/ml. The percentage recovery of was found to be in the range of 99.76-100.79%. The drug was subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, UV light and photolytic degradation. Validation experiments performed to demonstrate system suitability, specificity, precision, linearity, accuracy, interday assay, intraday assay, robustness, ruggedness, LOD, and LOQ. While estimating the commercial formulation there was no interference of excipients and other additives. Hence this method can be used for routine determination of candesartan cilexetil in bulk and their pharmaceutical dosage forms. The proposed method for stability study shows that there was appreciable degradation found in stress condition of candesartan.
ABSTRACT
BACKGROUND: Amplification of the MYC gene is reported to be associated with the development of head and neck squamous cell carcinoma (HNSCC). This study is focused to analyze the correlation between MYC gene amplification and various clinicopathological features and outcome in a cohort of 49 dysplastic and 187 primary head and neck lesions. METHODS: MYC gene amplification was assessed by differential polymerase chain reaction using primer sets from the MYC gene as target locus and DRD2 gene as the control locus. RESULT: The MYC gene amplification was detected in a total of 23.7% (56/236) head and neck lesions comprising 14.2% (7/49) dysplastic lesions and 26% (49/187) HNSCC samples. The clinicopathological association study between MYC gene amplification with the different clinical parameters like sex, tumor stage, tumor differentiation, lymph node status, tobacco habit and HPV 16/18 status determined significant association of MYC amplification with tumor progression (P = 0.009). Kaplan Meier analysis revealed MYC gene has no prognostic significance on survival in HNSCC. CONCLUSION: In conclusion, our results suggest that MYC gene amplification is associated with tumor progression in HNSCC.
Subject(s)
Carcinoma, Squamous Cell/genetics , Gene Amplification/genetics , Genes, myc/genetics , Head and Neck Neoplasms/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Child , Cohort Studies , Disease Progression , Female , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/virology , Human papillomavirus 16/isolation & purification , Human papillomavirus 18/isolation & purification , Humans , India , Lymph Nodes/pathology , Male , Middle Aged , Neoplasm Staging , Papillomavirus Infections/virology , Precancerous Conditions/genetics , Prognosis , Receptors, Dopamine D2/genetics , Sex Factors , Smoking , Young AdultABSTRACT
AIM: To investigate the complex interplay between human papilloma virus (HPV) infection and p53 gene alteration in 92 head and neck squamous cell carcinoma (HNSCC) and 28 leukoplakia samples from eastern India. METHODS: DNA isolated from the patient samples was subjected to HPV detection, loss of heterozygosity (LOH) analysis of the chromosome 17p region harbouring p53, genotyping at the p53 codon 72 locus and sequencing of the entire p53 gene to identify somatic mutations. Codon 72 heterozygotes carrying the p53 mutation were further cloned and resequenced to identify the allele harbouring the mutation. RESULTS: HPV positivity in the HNSCC samples was 69%; 21% of the HNSCC were found to harbour p53 mutations in the coding region of the gene. The absence of the p53 mutation in HPV positive tumours was statistically significant compared to the HPV negative tumours (p = 0.01), but the same did not hold true for p53 LOH (p = 1.0). Among the germline p53 codon 72 heterozygotes, the Pro allele was preferentially lost (p = 0.02) while the Arg allele was mutated in the majority of cases. The risk of HPV mediated tumourigenesis increased with the increase in number of Arg alleles at the codon 72 locus. CONCLUSION: It is proposed that genetic and epigenetic alteration of p53 follow distinct pathways during the development of HNSCC from normal epithelium via dysplasia. The p53 mutation and HPV mediated p53 inactivation possibly constitute two independent pathways of tumourigenesis.
Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/virology , Genes, p53 , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/virology , Papillomavirus Infections/complications , Adult , Carcinoma, Squamous Cell/pathology , Cell Transformation, Neoplastic/genetics , Chromosomes, Human, Pair 17/genetics , Female , Gene Silencing , Head and Neck Neoplasms/pathology , Humans , Leukoplakia, Oral/genetics , Leukoplakia, Oral/virology , Loss of Heterozygosity , Male , Middle Aged , Mutation , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Papillomavirus Infections/virologyABSTRACT
To understand the role of human papillomavirus (HPV) in recurrence of uterine cervical cancer (CA-CX) after radiotherapy, we have analyzed the HPV prevalence in the exfoliated cells of 56 patients and their corresponding plasma. HPV DNA was detected in exfoliated cells of 78% (44/56) patients (HPV-16, 68%; HPV-18, 14%; HPV-X [other than 16, 18], 11%; and mixed infection of HPV-16 and HPV-18 in three cases). HPV DNA in plasma was present in only 25% (11/44) of the HPV-positive exfoliated cells (positive predictive value, 100%; negative predictive value, 27%) with concordance in HPV types. The recurrence of the disease was significantly associated with the presence of HPV in the exfoliated cell (P= 0.01) and plasma (P= 0.007) as well as high viral load in the exfoliated cell (P= 0.0002). Kaplan-Meier disease-free estimates have also shown the significant association between HPV prevalence in plasma and recurrence of the disease (P= 0.045). Thus, it indicates that in postradiotherapy CA-CX patients, the high viral load in the exfoliated cell as well as HPV presence in the plasma samples could be used in early detection of the patients at increased risk for disease recurrence and progression.
Subject(s)
Carcinoma/radiotherapy , Carcinoma/virology , Neoplasm Recurrence, Local/epidemiology , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/virology , Adult , Aftercare/statistics & numerical data , Aged , Female , Humans , Middle Aged , Papillomavirus Infections/blood , Papillomavirus Infections/complications , Prevalence , Sensitivity and Specificity , Survival Analysis , Uterine Cervical Neoplasms/mortality , Vaginal Smears , Viral Load/statistics & numerical dataABSTRACT
OBJECTIVES: India, with its 43 million hepatitis B virus (HBV) carriers and absence of any national immunization programme, adds a substantial number of HBV infections to the HBV carrier pool yearly. The aim of this study was to assess the spread of HBV infection in families with an infected member and to identify the family members with the highest risk of infection in our community. METHODS: A total of 937 serum samples from 215 HBV-infected cases and 722 members of their households were screened prospectively for markers of HBV by commercial enzyme-linked immunosorbent assay. RESULTS: Among family members, 140 (19.4%) were HBsAg positive and 272 (37.6%) were negative for HBsAg but positive for either anti HBc or anti HBs. There were 145 HBsAg-positive adults among the index cases whose 133 adult siblings, 59 spouses and 59 mothers participated in the study. Interestingly, 28.81% mothers and 28.57% adult siblings of these adult index cases were positive for HBsAg compared with only 8.75% of their spouses (P < 0.001). Only 15.2% of the HBsAg-positive women in the childbearing age group were found to be HBeAg positive. CONCLUSIONS: Our results suggest that intrafamilial childhood horizontal transmission is important for HBV transmission in our community, and highlight the need for screening of adult siblings and mothers of adult HBsAg carriers in addition to their spouses and children.
Subject(s)
Carrier State/blood , Family Health , Hepatitis B/epidemiology , Mass Screening , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Cluster Analysis , Disease Transmission, Infectious/prevention & control , Enzyme-Linked Immunosorbent Assay , Female , Hepatitis B/blood , Hepatitis B/prevention & control , Hepatitis B/transmission , Hepatitis B Surface Antigens/blood , Humans , India/epidemiology , Infant , Male , Middle Aged , Mothers/statistics & numerical data , Risk Factors , Siblings , Surveys and QuestionnairesABSTRACT
One of the most promising strategies for cancer prevention is chemoprevention by daily used food and beverages. Black tea, the most widely consumed beverage, is a source of compounds with antioxidative, antimicrobial, antimutagenic and anticarcinogenic properties. Lung cancer is the most common cause of cancer deaths in both men and women worldwide. Over one million people around the world are likely to be killed by lung cancer due to increased tobacco smoking and environmental pollutants, especially car exhausts. Therefore chemopreventive intervention using black tea and its active components may be a viable means to reduce lung cancer death. In the present investigation, we used benzo(a)pyrene (BP) to induce lung carcinogenesis in mice for the assessment of potential apoptosis-inducing and proliferation-suppressing effects of theaflavins and epigallocatechin gallate, active components of black tea. Hyperplasia, dysplasia and carcinoma in situ evident in the carcinogen control group on the 8th, 17th and 26th weeks respectively, were effectively reduced after treatment with theaflavins and epigallocatechin gallate. Significant reduction in number of proliferating cells and increased number of apoptotic cells was also found on the 8th, 17th and 26th week of treatment with theaflavins and epigallocatechin gallate in BP-exposed mice. Our observation suggests a promising role for black tea polyphenols in the prevention of lung cancer.
Subject(s)
Biflavonoids/pharmacology , Catechin/analogs & derivatives , Cell Proliferation/drug effects , Lung Neoplasms/prevention & control , Tea/chemistry , Animals , Apoptosis/drug effects , Benzo(a)pyrene/toxicity , Carcinoma in Situ/physiopathology , Carcinoma in Situ/prevention & control , Catechin/pharmacology , Lung Neoplasms/veterinary , MiceABSTRACT
BACKGROUND: The predictive value of codon 72 arginine homozygosity at the p53 gene for human papilloma virus associated cervical cancer risk remains inconclusive. It has also been proposed that the inheritance of specific germline haplotypes based on three biallelic polymorphisms of p53 (intron 3 16 bp duplication, codon 72 Bst UI (Arg/Pro), and intron 6 Nci I restriction fragment length polymorphism at nucleotide 13494) is a better predictor of various cancer risks. AIMS: To determine the genotype and haplotype frequency of these three p53 polymorphisms in 61 patients with cervical squamous cell carcinoma and 94 ethnically matched controls from the eastern region of India and estimate the risk, if any, of specific genotypes and haplotypes. METHODS: Samples were genotyped by polymerase chain reaction followed by variant specific restriction enzyme digestion. Haplotypes were estimated by the maximum likelihood method using the expectation maximisation algorithm. RESULTS: Genotype distributions of the three polymorphisms in patients and controls showed a good fit to the Hardy-Weinberg equilibrium. The p53 codon 72 arginine homozygous genotype was significantly over represented in patients compared with controls. Those with the homozygous arginine genotype exhibited a 2.59 fold higher risk of developing squamous cell carcinoma of the uterine cervix. A significant risk was also seen with a combination of two haplotypes, 1-2-1 and 1-2-2. CONCLUSION: p53 codon 72 arginine homozygotes appear to be at greater risk of developing squamous cell carcinoma of the uterine cervix. The high risk haplotypes 1-2-1 and 1-2-2 also contain the arginine allele, further strengthening this conclusion.
Subject(s)
Carcinoma, Squamous Cell/genetics , Genes, p53/genetics , Genetic Predisposition to Disease , Uterine Cervical Neoplasms/genetics , Adult , Arginine/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Female , Genotype , Haplotypes , Humans , Middle Aged , Neoplasm Staging , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Polymorphism, Genetic , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virologyABSTRACT
OBJECTIVES: We have been done the detailed deletion mapping of chromosome (chr.) 8p21.3-23 to localize the candidate tumor suppressor gene(s) (TSGs) loci as well as studied the mechanism of activation of c-myc gene, located at chr.8q24.1, by analyzing the amplification/rearrangement/HPV integration within approximately 580 kb of c-myc locus in uterine cervical carcinoma (CaCx) of Indian patients. The association between the deletions in chr.8p21.3-23 and alterations in the c-myc locus has also been analyzed. METHODS: The deletion mapping of chr.8p21.3-23 was done by 15 microsatellite markers and the alterations in the c-myc locus were analyzed by Southern hybridization using the pal-1/c-myc/mlvi-4/HPV 16/18 probes in seven cervical intraepithelial neoplasia (CIN) and 55 primary uterine cervical carcinoma. The alterations in chr.8p/q have been correlated with the different clinicopathological parameters. RESULTS: Three discrete minimal deleted regions with high frequencies of loss of heterozygosity (LOH) (37-43%) were identified in the chr.8p23.1-23.2 (D1), 8p23.1 (D2), and 8p 21.3-22 (D3) regions within 0.41-4.62 Mb. The deletion in the D1 region was significantly associated with the deletion in the D2 region (P = 0.03), whereas the deletion in D2 was marginally associated with the deletion in the D3 region (P = 0.07). The alterations in the c-myc locus were seen in 43% of the samples. About 35% of the samples showed coalterations in both arms of chr.8. No significant association was observed with the alterations in chr.8p/q as well as with the different clinicopathological parameters. CONCLUSIONS: The deletions in chr.8p21.3-23 and the alterations in the c-myc locus are independently associated with the development of CaCx. The D1-D3 regions in chr.8p21.3-23 could harbor candidate TSGs associated with the development of this tumor. The c-myc gene was activated by amplification/rearrangement at the pal-1/c-myc/mlvi-4 loci as well as HPV integration in the pal-1 locus in this tumor.
Subject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 8/genetics , Uterine Cervical Neoplasms/genetics , Adult , Aged , Chromosome Mapping , Female , Genes, Tumor Suppressor , Genes, myc/genetics , Genetic Predisposition to Disease , Humans , India , Loss of Heterozygosity , Middle Aged , Papillomaviridae , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virologyABSTRACT
Deletion in the 22.9 -Mb chromosomal (chr.) 8p21.3-23 region has been shown to be necessary for the development of breast carcinoma (CaBr). In this study, we have attempted to detect the minimal deleted region(s) in the chr.8p21.3-23 region in 62 primary breast lesions having 56 CaBr tumors and six other breast lesions of Indian patients using 15 microsatellite markers. The loss of heterozygosity (LOH) was observed for at least one marker in 96.4% (54/56) of the CaBr samples. Three discrete minimal deleted regions with high frequencies of LOH (39-65%) were identified in the chromosomal 8p23.1-23.2 (D1), 8p23.1 (D2) and 8p 21.3-22 (D3) regions within 2.03, 0.41, 2.47 Mb, respectively. No significant correlation was observed with the high deleted regions and the different clinicopathological parameters. Interestingly, 51.8% (29/56) CaBr samples showed either loss of chr.8p or interstitial deletions in this arm, indicating the importance of chr.8p in the development of CaBr. The pattern of allelic loss in the bilateral lesions had indicated that the lesions were clonal in origin and probably the deletion in the D3 region was the early event among the D1-D3 regions. Thus, our data have indicated that the D1-D3 regions could harbor candidate tumor suppressor gene(s) (TSGs) associated with the development of CaBr.
Subject(s)
Breast Neoplasms/genetics , Chromosomes, Human, Pair 8/genetics , Fibroadenoma/genetics , Adult , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , DNA, Neoplasm/genetics , Female , Fibroadenoma/epidemiology , Fibroadenoma/pathology , Genes, Tumor Suppressor , Humans , India/epidemiology , Loss of Heterozygosity , Microsatellite RepeatsABSTRACT
BACKGROUND & OBJECTIVES: Deletions in chromosome 8 (chr.8) have been shown to be necessary for the development of head and neck squamous cell carcinoma (HNSCC). Attempts have been made in this study to detect the minimal deleted region in chr.8 associated with the development of HNSCC in Indian patients and to study the association of clinicopathological features with the progression of the disease. METHODS: The deletion mapping of chr.8 was done in samples from 10 primary dysplastic lesions and 43 invasive squamous cell carcinomas from the head and neck region of Indian patients to detect allelic alterations (deletion or size alteration) using 12 highly polymorphic microsatellite markers. The association of the highly deleted region was correlated with the tumour node metastasis (TNM) stages, nodal involvement, tobacco habit and human papilloma virus (HPV) infection of the samples. RESULTS: High frequency (49%) of loss of heterozygosity (LOH) was seen within 13.12 megabase (Mb) region of chromosomal 8p21.3-23 region in the HNSCC samples, whereas the dysplastic samples did not show any allelic alterations in this region. The highest frequency (17%) of microsatellite size alterations (MA) was observed in the chr.8p22 region. The loss of short arm or normal copy of chr.8 and rare bi-allelic alterations were seen in the stage II-IV tumours (939, 5184, 2772, 1319 and 598) irrespective of their primary sites. The highly deleted region did not show any significant association with any of the clinical parameters. However, HPV infection was significantly associated (P < 0.05) with the differentiation grades and overall allelic alterations (LOH/MA) of the samples. INTERPRETATION & CONCLUSION: Our data indicate that the 13.12 Mb deleted region in the chromosomal 8p21.3-23 region could harbour candidate tumour suppressor gene(s) (TSGs) associated with the progression anti invasion of HNSCC tumours in Indian patients.
Subject(s)
Carcinoma, Squamous Cell/genetics , Chromosome Deletion , Chromosomes, Human, Pair 8 , Head and Neck Neoplasms/genetics , Alleles , Base Sequence , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , DNA Primers , Female , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/virology , Humans , India , Loss of Heterozygosity , Male , Papillomaviridae/isolation & purificationABSTRACT
BACKGROUND: Deletions in chromosome 3 occur frequently in uterine cervical carcinoma (CA-CX). The common consensus regions deleted during CA-CX development are not well defined, and have not been correlated with tumour progression. AIMS: To define specific regions of chromosome 3 deleted during development of CA-CX and to correlate these with clinicopathological data. METHODS: Deletion mapping of chromosome 3 was done in seven cervical intraepithelial neoplasia (CIN) and 43 primary CA-CX samples using 20 highly polymorphic microsatellite markers. RESULTS: Deletions of chromosome 3 were significantly associated with tumour progression. High frequencies (33-53%) of loss of heterozygosity (LOH) were found in 3p26.1, 3p22.3, 3p21.2, and 3p13, suggesting the location of putative tumour suppressor genes (TSGs) in these regions. Among these four regions, deletions in 3p21.2 were suggested to occur early during CA-CX development. A significant correlation was found between LOH at 3p26.1 and 3p22.3 with tumour progression from stage I/IIB to stage III/IV. No association was found with the highly deleted regions and human papillomavirus positivity, parity, or menopausal status. Microsatellite size alteration was seen in only seven of the samples. However, rare biallelic alterations were seen in and around the highly deleted regions. Loss of normal copy of chromosome 3 and interstitial alterations in chromosome 3p were seen in some samples. CONCLUSION: These four regions on chromosome 3p may be differentially deleted during specific stages of CA-CX development. The putative TSGs located in these regions may have a cumulative effect on tumour progression.