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

To investigate the possible causal association between squamous-cell carcinomas of the oral cavity and use of toombak, we retrospectively compared the history of use of this substance in 375 patients with squamous-cell carcinomas of the lip, buccal cavity and floor of mouth, and 271 patients with squamous carcinomas of the tongue, palate and maxillary sinus, with 204 patients exhibiting non-squamous oral and non-oral malignant neoplasms and 2,820 individuals who had no malignancy, selected from the general population. The study revealed that the high prevalence of oral cancer in the Sudan is largely due to chronic use of toombak. The adjusted ORs associated with toombak dipping for the first case group, cancer of the lip, buccal cavity and floor of mouth in comparison with the hospital and population control groups, were 7.3 and 3.9 (95% confidence limits, 4.3-12.4 and 2.9-5.3) respectively and among long-term users the adjusted ORs were 11.0 and 4.3 (95% confidence limits, 4.8-25.1 and 2.9-6.3) respectively. The elevated risk found when investigating intra-oral cancers of sites in direct contact with toombak quid compared to those with little or no contact, confirms the hypothesis that direct contact with tissues is an important factor in tobacco carcinogenesis in the mouth. The increased risk associated with the use of toombak is of particular concern in view of its wide consumption in the Sudan.
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PMID:Toombak dipping and cancer of the oral cavity in the Sudan: a case-control study. 759 Dec 52

Tobacco (smoking and smokeless) use and excessive consumption of alcohol are considered the main risk factors for oral cancer (ICD9 140-149). Conspicuous national and international variations in oral cancer incidence and mortality rates, as well as observations in migrant populations, raise the possibility that diet and nutritional status could be an important etiologic factor in oral carcinogenesis. As shown in this report, abuse of alcohol and tobacco has serious nutritional implications for the host, and generates increased production of reactive free radicals as well as eliciting immunosuppression. Maintenance of optimal competence of the immune system is critical for cancer surveillance. Active oxygen species and other reactive free radicals mediate phenotypic and genotypic alterations that lead from mutation to neoplasia. Consequently, the most widely used chemopreventive agents against oral cancer (e.g., vitamins A, E, C, and beta-carotene) are anti-oxidants/free radical scavengers. These anti-oxidants, both natural and synthetic, neutralize metabolic products (including reactive oxygen species), interfere with activation of procarcinogens, prevent binding of carcinogens to DNA, inhibit chromosome aberrations, restrain replication of the transformed cell, suppress actions of cancer promoters, and may even induce regression of precancerous oral lesions such as leukoplakia and erythroplakia. Malnutrition is characterized by marked tissue depletion of anti-oxidant nutrients, including GSH (gamma-glutamyl-cysteinyl-glycine), a key cellular anti-oxidant as well as a modulator of T-cell activation. GSH or its precursor cysteine inhibits activation of the nuclear transcription factor kB(NFkB), and has been shown to be protective against chemically induced oral cancer and leukoplakia. Alcohol-, tobacco-, and/or malnutrition-induced immunosuppression promotes impaired salivary gland function and oral mucosal immunity, a prominent reduction in the number of helper CD4 cells with less marked changes in number of suppressor T-cells, and depressed NK cell activity, among others. These suggest a breakdown in capacity or the malnourished to mount effective tumor surveillance. This review article underscores the compounding but important roles of nutritional/dietary factors in the long-established causal link between abuse of alcohol and tobacco (smoking and smokeless) and oral cancer.
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PMID:Bionutrition and oral cancer in humans. 763 67

The habit of betel quid chewing, common in South-East Asia and the South Pacific islands, is causally associated with an increased risk of oral cancer. Reactive oxygen species formed from polyphenolic betel quid ingredients and lime at alkaline pH have been implicated as the agents responsible for DNA and tissue damage. To determine whether hydroxyl radical (HO.) is generated in the human oral cavity during chewing of betel quid, the formation of o- and m-tyrosine from L-phenylalanine was measured. Both o- and m-tyrosine were formed in vitro in the presence of extracts of areca nut and/or catechu, transition metal ions such as Cu2+ and Fe2+ and lime or sodium carbonate (alkaline pH). Omission of any of these ingredients from the reaction mixture significantly reduced the yield of tyrosines. Hydroxyl radical scavengers such as ethanol, D-mannitol and dimethylsulfoxide inhibited the phenylalanine oxidation in a dose-dependent fashion. Five volunteers chewed betel quid consisting of betel leaf, areca nut, catechu and slaked lime (without tobacco). Their saliva, collected after chewing betel quid, contained high concentrations of p-tyrosine, but no appreciable amounts of o- or m-tyrosine. Saliva samples from the same subjects after chewing betel quid to which 20 mg phenylalanine had been added contained o- and m-tyrosine at concentrations ranging from 1010 to 3000 nM and from 1110 to 3140 nM respectively. These levels were significantly higher (P < 0.005) than those of subjects who kept phenylalanine in the oral cavity without betel quid, which ranged from 14 to 70 nM for o-tyrosine and from 10 to 35 nM for m-tyrosine. These studies clearly demonstrate that the HO. radical is formed in the human oral cavity during betel quid chewing and is probably implicated in the genetic damage that has been observed in oral epithelial cells of chewers.
Carcinogenesis 1995 May
PMID:Ortho- and meta-tyrosine formation from phenylalanine in human saliva as a marker of hydroxyl radical generation during betel quid chewing. 776 85

We examined the incidence of human papillomavirus (HPV) in intraoral cancers from 64 patients as determined by the highly sensitive technique of "hot start" polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded tissues. Polymerase-chain-reaction-amplified HPV DNA was detected in the carcinomas of 16 patients (25%). The percentage of men in the HPV-positive (HPV+) group was greater than that in the HPV-negative (HPV-) group (86% versus 68%), but the difference was not statistically significant. There was no intraoral site preference for the HPV+ tumors. The mean age of viral-positive and -negative groups was similar (55 versus 53.8 yr). Three of 16 HPV+ patients (19%) had never smoked cigarettes; however, 16% of the HPV- group had also never smoked. Of interest, 38% of patients interviewed had occupation-related exposures that may have contributed to their carcinogenesis, and a disproportionate percentage of these patients (57%) were from the HPV+ group. There were no statistically significant differences between HPV+ and HPV- cases regarding T stage, clinical stage, and tumor differentiation. The disease-free interval did not differ significantly for HPV+ and HPV- patients in total nor when patients were stratified for tumor stage and clinical stage. The only group that showed some difference in outcome was that of the stage III/IV patients with oral cancer. We observed a shorter survival time for the HPV+ patients as compared with the HPV- patients (P = 0.09). We conclude that, in general, HPV is associated with a minority of intraoral cancers and its presence is not predictive of patient outcome.
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PMID:HPV detection using "hot start" polymerase chain reaction in patients with oral cancer: a clinicopathological study of 64 patients. 782 4

beta-carotene and other antioxidant nutrients, such as vitamin E, are well suited for widespread preventive use because they are nontoxic and easily given in supplement form. Intervention trials designed to show a reduction of cancer incidence in the general population are logistically and practically impossible for most types of cancer, including cancer of the oral cavity. Thus evidence for chemoprevention must be indirect, using laboratory and animal models, epidemiologic surveys, and trials showing reversal of premalignant lesions or cancer prevention in high-risk groups. In several animal models, beta-carotene and other antioxidant nutrients inhibit oral carcinogenesis. Epidemiologic studies consistently relate low intake of these nutrients with high cancer risk. Smokers have lower beta-carotene levels in plasma and oral mucosal cells than nonsmokers. Eight clinical trials have now shown that beta-carotene and vitamin E produce regression of oral leukoplakia, but chemoprevention studies in oral leukoplakia have limitations, which we review. All available evidence supports a significant role for antioxidant nutrients in preventing oral cancer.
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PMID:Emerging role of beta-carotene and antioxidant nutrients in prevention of oral cancer. 784 Sep 19

The chromosome-damaging effects of urine concentrates (UCs) from tobacco plus areca nut (T/AN) chewers (a highly popular habit and a major risk factor for oral cancer in India) were evaluated on Chinese hamster ovary (CHO) cells employing two cytogenetic end-points, namely chromosome aberration (CA) and sister chromatid exchange (SCE) frequencies. Urine creatinine levels were comparable between controls and T/AN chewers. CA and SCE frequencies in CHO cells were found to be elevated significantly (P < 0.001) following treatment with UCs prepared from T/AN chewers (UC-T/AN chewers) as well as with UCs of non-chewer controls (UC-control subjects). Moreover, elevation of these two parameters by UC-T/AN chewers was significantly higher in comparison to that of UC-controls. The results of the present study indicated that besides the oral cavity, which is a target organ for T/AN chewers, mutagens/carcinogens in tobacco and areca nut might be playing a causative role in cancer of the urinary bladder as well.
Carcinogenesis 1995 Feb
PMID:Urine of tobacco/areca nut chewers causes genomic damage in Chinese hamster ovary cells. 785 49

Carcinogenesis is a multi-step process including aberrant expression of two interacting classes of genes--oncogenes and tumour suppressor genes. With recent technological advances, it is feasible to identify the various molecular lesions underlying the different stages of neoplasia. Squamous cell carcinomas of the head and neck, although representing 2-4% of the malignancies in the West, comprise a large fraction (40%) of total cancers in India, posing a major health problem. Further, epidemiological and experimental evidence unequivocally confirms a causal association between tobacco chewing habit, highly prevalent in India, and oral cancers. Thus, the oral cancers offer an excellent in vivo system for the study of the environmental tobacco-carcinogen induced molecular alterations in the malignancy, and associated premalignant lesions such as leukoplakia. With a view to elucidating the molecular lesions involving oncogenes in oral carcinogenesis, we have investigated myc/ras/EGF-R activation by amplification, point mutation, gene rearrangement and allelic losses. Further, a functionally activated potent transforming gene was detected in a NIH3T3 transfection/tumorigenicity assay, unrelated to myc/ras/EGF-R. Studies on the involvement of p53 gene in oral cancer, indicates p53 allelic loss as an event observed in leukoplakia and tumour tissues. Advanced oral cancer stages demonstrate cumulative molecular aberrations, with greater than 95% samples showing oncogene involvement, thus indicating a multi-step process of oral carcinogenesis. The review presents a comparative picture of the oral malignancies seen in Western countries and India, significance of molecular lesions and future perspectives of oncogenes and tumour suppressor gene involvement in oral cancer.
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PMID:Molecular lesions in human oral cancer: the Indian scene. 791 88

Sister chromatid exchange (SCE) values were determined in the lymphocytes of 24 oral cancer patients before therapy and in the lymphocytes of 24 control persons standardized with respect to sex, age and smoking habits. Oral cancer patients showed significantly elevated SCE values (mean 7.82 versus 6.42). In both groups the highest SCE values were found in the subgroups with the highest alcohol consumption. A significant correlation between SCE and gamma-glutamyltranspeptidase (GGT) values by Spearman correlation analysis was detected in the combined group (cancer patients and control persons) (n = 32, r = 0.40, P = 0.023). The SCE values in the oral cancer patients were weakly correlated (Pearson) to DNA adduct levels (n = 22, r = 0.39, P = 0.068) and DNA single-strand breakage frequencies (n = 12, r = 0.56, P = 0.054) in lymphocytes. The correlation (Pearson) between SCE values and DNA strand breakage values in lymphocytes was significant (n = 10, r = 0.67, P = 0.036) in smoking cancer patients. The increase of SCE values with respect to alcohol drinking habits underlines epidemiologic findings that alcohol is an important co-carcinogen in many cancers, especially in oral cancers. Because of the influences on SCE and adduct levels in lymphocytes, alcohol drinking habits should be controlled as broadly as possible in biomarker studies.
Carcinogenesis 1994 Aug
PMID:Sister chromatid exchange frequencies in lymphocytes of oral cancer patients seem to be influenced by drinking habits. 791 76

The significance of the interaction between alcohol and tobacco in causing head and neck cancers is well documented. Our previous reports on in vitro studies using aqueous and organic extracts as well as cytogenetic studies among pan masala consumers have conclusively shown the genotoxic potential of pan masala--a dry mixture of the areca nut, lime, catechu, unspecified flavouring agents, etc., often containing tobacco in it and is widely consumed in India. Now in the present report, the clastogenic effect of ethanol and pan masala in different combinations was evaluated on Chinese hamster ovary cells utilizing chromosome aberration (CA) frequency as an endpoint. An ethanol concentration of up to 2.0% had no effect on CA/cell value. The low-dose continuous treatment and high-dose short-term pre-, post- and simultaneous treatment of ethanol and aqueous extract of pan masala with and without tobacco yielded dose-dependent elevations in CA frequency, compared to any of these two substances alone. Thus, these results provide evidence that alcohol consumption may potentially increase the risk of oral cancer among pan masala chewers.
Carcinogenesis 1994 Sep
PMID:Ethanol potentiates the clastogenicity of pan masala--an in vitro experience. 792 97

Using the hamster cheek pouch oral cancer model, we have performed a comprehensive analysis of the cytogenetic changes in hamster oral keratinocytes during 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis. Tumour induction in the hamster cheek pouch required repeated application of the carcinogen for 14 weeks. We have found that this hamster oral cancer model to be suitable for cytogenetic studies. Unlike human oral cancers where chromosome breaks have been shown, this is only infrequently observed in DMBA-treated hamster oral keratinocytes. Of importance is the finding that at the beginning of the second week of DMBA treatment, there is a significant increase of karyotypes demonstrating tetraploid or near-tetraploidy. We propose that the significant increase in hamster oral keratinocytes exhibiting tetraploidy be further evaluated as a marker of premalignancy/malignancy.
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PMID:Sequential cytogenetic alterations in hamster oral keratinocytes during DMBA-induced oral carcinogenesis. 795 Aug 40


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