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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Shamma, a complex mixture of powdered tobacco, slaked lime, ash, oils, spices and other additives, has been linked to oral cancer in Saudi Arabia. Shamma varies in colour and odour due to the nature of the additives which characterize different brands. Using the Ames Salmonella assay, a chloroform extract of a brand named 'white shamma' (WSH) was found to be mutagenic, while that of a brand called 'brown shamma' (BSH), which is known to contain mint as a flavouring agent, was found to be non-mutagenic. Using HPLC, a mutagenic and a non-mutagenic fraction were isolated from the extract of BSH. The non-mutagenic fraction of BSH was found to neutralize the genotoxic effect of the mutagenic fraction when the two were recombined. A chloroform extract of mint showing no mutagenic activity in the Ames assay effectively inhibited the mutagenicity of carcinogens/mutagens like benzo[a]-pyrene, aflatoxin B1, methylmethane sulfonate and extract of WSH. A carcinogenicity assay designed to test the effects of WSH and BSH in the hamster cheek pouch model showed that the former was tumorigenic, while the latter was not. However, when crushed leaves of mint were mixed with powdered WSH (in 1:1 proportion), the tumorigenic effect of the latter was abolished. These data strongly suggested that mint has a chemopreventive effect against shamma-induced carcinogenesis, which could be due to its antimutagenic properties.
Carcinogenesis 1998 Oct
PMID:Mint prevents shamma-induced carcinogenesis in hamster cheek pouch. 980 61

Risk of oral cancer has been associated with exposure to tobacco smoke, alcohol and with genetic predisposition. The aromatic amines and their metabolites, a class of carcinogens present in tobacco smoke, undergo metabolism (activation or detoxification) through an N- or O-acetylation pathway by the polymorphic enzymes, N-acetyltransferases (NAT)1 or NAT2. The genes that encode these enzymes, NAT1 and NAT2, have a variety of high and low activity alleles and we analyzed these genetic polymorphisms in 62 oral squamous cell carcinoma cases, and 122 healthy control subjects from Japan. NAT1 alleles tested were NAT1*3 (C1095A), NAT1*4 (functional reference allele), NAT1*10 (T1088A,C1095A), NAT1*11(9 bp deletion), NAT1*14 (G560A), NAT1*15 (C559T) and NAT1*17 (C190T). No low activity alleles (NAT1*14, NAT1*15 and NAT1*17) were observed in these Japanese subjects. We observed significantly increased risk [odds ratio 3.72; 95% confidence interval (CI) 1.56-8.90; P < 0.01] associated with the NAT1*10 allele, an allele that contains a variant polyadenylation signal. Stratifying by smoking status we found odds ratios of 5.9 (95% CI 1.13-30.6; P < 0.05) for non-smokers with the NAT1*10 allele and 3.1 (95% CI 1.09-9.07; P < 0.05) for smokers, but these risks were not significantly different from each other. Thus, we did not observe that NAT1*10 alleles confer differential risk among smokers and non-smokers. NAT2 rapid acetylation genotype was not a significant risk factor for oral cancer in this Japanese study population. This is the first study to test for oral cancer risk associated with polymorphism in the NAT1 and NAT2 genes, and these positive findings in our pilot study, while based on small numbers, suggest that the NAT1*10 allele may be a genetic determinant of oral squamous cell carcinoma among Japanese people.
Carcinogenesis 1998 Oct
PMID:A pilot study testing the association between N-acetyltransferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people. 980 62

We showed differential expression of HSP70 during oral tumorigenesis. The precise functional role of HSP70 overexpression in the pathogenesis of betel and tobacco related oral cancer remains to be determined. To evaluate the utility of HSP70 as an indicator of the biological stress experienced by tumour cells or the malignant potential of oral epithelial lesions and predicting clinical outcome, its expression was assessed in different stages of oral carcinogenesis by immunohistochemical analysis and correlated with clinicopathological parameters. Overexpression of HSP70 protein was observed in 38 of 64 (59%) dysplastic lesions and 92 of 125 (74%) oral squamous cell carcinomas (SCCs) which included 76 of 105 cases (72%) of primary oral SCCs and 16 of 20 (80%) of recurrent oral SCCs. A significant correlation of HSP70 expression was observed with severity of dysplasia (P = 0.0006767), poor histological differentiation of primary tumours (P = 0.0184348), increase primary tumour size (P = 0.0221103) and consumption of betel and tobacco (P < 0.01). Follow-up studies showed that in patients with premalignant lesions the median transition time (premalignancy to malignancy) was significantly shorter in HSP70 overexpressing cases than those showing basal level of HSP70 (P = 0.012). Oral cancer patients with elevated levels of HSP70 showed decreased median disease-free survival time (no recurrence/metastasis) than those showing basal HSP70 immunoreactivity (P = 0.0246). The results suggest that HSP70 expression may not be a mere marker of biological stress but may also be implicated in the pathogenesis of oral cancer.
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PMID:Expression of 70-kDa heat shock protein in oral lesions: marker of biological stress or pathogenicity. 993 Mar 61

To initially analyze the genomic abnormalities in human oral squamous cell carcinoma, DNA extracted from each of four oral carcinoma cell lines (Ca9-22, HO-1-u-1, HSC-2, KB) was examined using restriction landmark genomic scanning (RLGS), a method especially conducive to detection of amplifications and rearrangements of genomic DNA. Isolated cell line and normal oral epithial DNAs were sequentially cleaved with specific restriction enzymes, radiolabelled and separated in two-dimensional gel electrophoreses. Thirteen distinct fragments were commonly amplified in the oral cancer cell lines, six of which were evident in all samples. These results suggest genetic alterations characteristic of oral squamous cell carcinogenesis.
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PMID:Genomic alterations in oral squamous cell carcinoma cell lines detected by two-dimensional gel analysis. 993 Mar 63

A probability-based multivariate statistical algorithm combining partial least-squares (PLS) and logistic regression was developed to identify the development stages of oral cancer through analysis of autofluorescence spectra of oral tissues. Tissues were taken from a 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis model. Analyses were conducted at various excitation wavelengths, ranging from 280 nm to 400 nm in 20 nm increments, to assess classification performance at different excitations. For each excitation the PLS analysis and logistic regression were combined, on the basis of cross validation, to calculate the posterior probabilities of samples belonging to four stages of cancer development: normal tissues, hyperplasia, dysplasia and early cancers and frankly invasive cancers. Results showed that the 320 nm excitation wavelength optimally classified the cancer development stages: the accuracy rates for identifying samples at that excitation were 91.7%, 83.3%, 66.7% and 83.3% for the four respective stages. The average accuracy rate was 81.3%. These results suggest that the algorithm described in this study might be useful for the detection of human oral cancers.
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PMID:A probability-based multivariate statistical algorithm for autofluorescence spectroscopic identification of oral carcinogenesis. 1021 79

Dysregulation of the epidermal growth factor receptor (EGFR) is one of the most frequently studied molecular events leading to oral carcinogenesis. Overexpression of EGFR is a common event in many human solid tumors. Elevated levels of EGFR mRNA in human cancer occur with and without gene rearrangement. Structural alterations in the receptor can also result in the dysregulation of the EGFR pathway. EGFR overexpression without gene re-arrangement is frequently observed in human oral cancers. However, little is known whether structural alterations in the receptor or perturbations in the EGFR pathway contribute to oral carcinogenesis. Several preliminary studies suggest that EGFR-targeted therapeutic approaches might be successful in controlling oral cancer.
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PMID:Epidermal growth factor receptor (EGFR) biology and human oral cancer. 1021 11

Oral cancer is the most common cancer in males and third most common in females in India, the main causative agent being the use of chewing tobacco with or without betel quid (BQ). However, nothing is known about the role of the host metabolic genes in oral cancer in ethnic Indian population. In this study, the prevalence of GSTM1 and GSTT1 null genotypes (GSTM1*2 and GSTT1*2) in oral premalignant leukoplakia cases and controls was ascertained in genomic DNA by a multiplex PCR technique. Biopsies taken from 98 oral leukoplakia patients and exfoliated cells from 82 healthy controls both of Indian ethnicity were analysed. GSTM1*1 (active) was present in 83% and GSTT1*1 (active) was present in 78% of all control subjects, while prevalence of GSTM1*2 and GSTT1*2 null genotypes was significantly higher among oral leukoplakia cases. The prevalence of GSTM1*2 in leukoplakia cases was 81.6% compared with 17% in controls [odds ratio (OR), 22; 95% confidence interval (CI), 1047] and GSTT1*2 was 75.5% in the cases versus 22% in controls (OR, 11; 95% CI, 5-22). Combined null genotypes of GSTM1 and GSTT1 prevailed in 60.2% of the cases with none detected in controls. Glutathione S-transferase M1 and T1 enzymes are both known to catalyse detoxification of reactive oxygen species, lipid peroxidation products and tobacco-derived carcinogens that have been found in the saliva of BQ/tobacco chewers. Our results, still requiring confirmation by a larger study, demonstrate that the null genotypes of both GSTM1 and GSTT1 increase with high penetrance, separately or in combination, the risk for developing leukoplakia in an Indian ethnic population.
Carcinogenesis 1999 May
PMID:Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers. 1033 89

One of the most important components of G1 checkpoint is the retinoblastoma protein (pRB110). The activity of pRB is regulated by its phosphorylation, which is mediated by genes such as cyclin D1 and p16/MTS1. All three genes have been shown to be commonly altered in human malignancies. We have screened a panel of 26 oral squamous cell carcinomas (OSCC), nine premalignant and three normal oral tissue samples as well as eight established OSCC cell lines for mutations in the p16/MTS1 gene. The expression of p16/MTS1, cyclin D1 and pRB110 was also studied in the same panel. We have found p16/MTS1 gene alterations in 5/26 (19%) primary tumours and 6/8 (75%) cell lines. Two primary tumours and five OSCC cell lines had p16/MTS1 point mutations and another three primary and one OSCC cell line contained partial gene deletions. Six of seven p16/MTS1 point mutations resulted in termination codons and the remaining mutation caused a frameshift. Western blot analysis showed absence of p16/MTS1 expression in 18/26 (69%) OSCC, 7/9 (78%) premalignant lesions and 8/8 cell lines. One cell line, H314, contained a frameshift mutation possibly resulting in a truncated p16/MTS1 protein. pRB was detected in 14/25 (56%) of OSCC but only 11/14 (78%) of these contained all or some hypophosphorylated (active) pRB. In premalignant samples, 6/8 (75%) displayed pRB, and all three normal samples and eight cell lines analysed contained RB protein. p16/MTS1 protein was undetectable in 10/11 (91%) OSCCs with positive pRB. Overexpression of cyclin D1 was observed in 9/22 (41%) OSCC, 3/9 (33%) premalignant and 8/8 (100%) of OSCC cell lines. Our data suggest p16/MTS1 mutations and loss of expression to be very common in oral cancer cell lines and less frequent in primary OSCC tumours. A different pattern of p16/MTS1 mutations was observed in OSCC compared to other cancers with all the detected p16/MTS1 mutations resulting in premature termination codons or a frameshift. The RB protein was expressed in about half (44%) of OSCCs and its expression inversely correlated with p16/MTS1 expression. In conclusion, we show that abnormalities of the RB pathway are a common mechanism of oral carcinogenesis.
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PMID:Role of p16/MTS1, cyclin D1 and RB in primary oral cancer and oral cancer cell lines. 1038 82

Lip cancer (140 ICD-9) is a form of oral cancer that has a distinctive global epidemiology. This review summarises global incidence rates for male and female lip cancer with the aid of cancer atlases. High male lip cancer rates are reported for regions of North America (12.7 per 100 000 per annum), Europe (12.0 per 100 000 per annum) and Oceania (13.5 per 100 000 per annum), while it is virtually unknown in parts of Asia. Factors commonly cited as important in the aetiology of lip cancer include solar radiation, tobacco smoking and viruses. An attempt is made to summarise the evidence for factors that may be important in lip carcinogenesis. While incidence rates are generally stable or falling among males worldwide, they are rising in many female populations. The aetiology of the disease is far from established and much information regarding its pathogenesis is based on anecdotal rather than case-controlled epidemiological evidence. The epidemiology of lip cancer supports the proposal that the lip should be considered as a distinct cancer site, rather than being included with other forms of intraoral cancer.
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PMID:The epidemiology of lip cancer: a review of global incidence and aetiology. 1048 63

Mutations of the p53 tumor suppressor gene have been found to be the single most frequent event in human cancers. In India and other southeast Asian countries tobacco chewing with betel quid was attributed to be the major factor in oral carcinogenesis. We have analyzed 72 untreated primary oral squamous cell carcinomas (SCCs) for mutations in the tumor suppressor gene p53 exons 4-9 by PCR-SSCP and DNA sequencing. Sequencing analysis revealed 16 missense mutations, one silent mutation in codon 307 and four A to G substitution polymorphism in codon 213. The incidence of p53 mutation was 21% (15 of 72) excluding the polymorphism and the silent mutation. Eight mutations were clustered in codons 266-282 of exon 8. Of the total mutation events 37.5% were G to A transitions and 31.3% were G to T transversions. These results indicate the possible involvement of tobacco derived nitrosamines and their adducts in the genesis of oral cancer among Indians.
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PMID:Low incidence of p53 mutations in betel quid and tobacco chewing-associated oral squamous carcinoma from India. 1056 19


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