Risk factors for oral cancer in newly diagnosed patients aged 45years and younger: a case-control study in Southern England

BACKGROUND: This case-control study aimed to identify the risk factors for oral cancer in patients aged 45 years and under. METHODS: Patients were recruited over a 3-year period between 1999 and 2001 from 14 hospitals in the southeast of England, UK. RESULTS: Fifty-three (80%) newly diagnosed patients with squamous cell carcinoma (SCC) of the oral cavity participated. The mean age of cases at diagnosis was 38.5 years (SD = 7.0) and 53% were male. Patients were interviewed about main risk factors of tobacco, alcohol, cannabis and their consumption of fresh fruit and vegetables in the past. Ninety-one matched control patients were also recruited. Odds ratios (ORs) and 95% confidence intervals (CI) were obtained from adjusted conditional logistic analyses. Significantly elevated ORs were evidenced amongst males who had started to smoke under the age of 16 years (OR = 14.3; 95% CI: 1.1-178.8). A significant reduction in risk was also shown for ex-smokers (OR = 0.2; 95% CI: 0.5-0.8). Consumption of alcohol in excess of recommended amounts also produced an eightfold risk in males (OR = 8.1; 95% CI: 1.6-40.1) and over a fourfold risk of oral cancer from the consumption of excessive amounts of alcohol and having ever smoked (OR = 4.4; 95% CI: 1.1-17.7). CONCLUSION: The study shows that the traditional behavioural risk factors are present in younger people diagnosed with oral cancer. The relatively short duration of exposure and the substantial number of cases without any known risk factors, particularly amongst females, however, suggest that factors other than tobacco and alcohol may also be implicated in the development of oral cancer in a proportion of these younger patients.No Full Tex

Copper stimulates human oral fibroblasts in vitro: a role in the pathogenesis of oral submucous fibrosis

Copper is implicated in the pathogenesis of several fibrotic disorders. Areca nut has been shown to have a high copper content and areca chewing is associated with oral submucous fibrosis (OSF). The effects of copper on human oral fibroblasts were investigated in vitro. Human oral fibroblasts were incubated with copper chloride (CuCl2) at concentrations ranging from 0.01 microM to 500 microM for 24 h, and in vitro cell proliferation was assayed by incorporation of tritiated-thymidine; soluble and non-soluble collagen synthesis was assayed using tritiated-proline. Addition of copper chloride at concentrations ranging from 0.1 microM to 50 microM increased the collagen synthesis by the oral fibroblasts compared with growth without copper (P<0.05). The addition of copper chloride neither increased the synthesis of non-collagenous proteins by the fibroblasts nor influenced their proliferation rate. We conclude that copper upregulates collagen production in oral fibroblasts. This appears to be concentration dependent, with peak collagen synthesis at 50 microM CuCl2. These in vitro results taken together with the recent findings of copper in oral biopsies from OSF subjects support the hypothesis that copper in areca nut acts as a mediator of OSF.No Full Tex

Squamous cell carcinoma of the oral cavity in patients aged 45 years and under: a descriptive analysis of 116 cases diagnosed in the South East of England from 1990 to 1997

Background: there is, currently, much anecdotal and some epidemiological evidence for a rise in oral cancer rates amongst younger individuals, many of whom have had no exposure to traditional risk factors such as tobacco and heavy alcohol use, or at least not the exposure over decades usually associated with this disease. The probity of this assertion and the presence or absence of traditional risk factors needs further evidence. Objectives: this paper describes the demography and the exposure to potential risk factors amongst a cohort aged 45 years and younger, diagnosed with squamous cell carcinoma of the oral cavity between 1990 and 1997 from the South East of England. Materials and methods: eligible patients registered with a cancer registry were included in this retrospective study. Information was accessed from the database and by a postal questionnaire survey. The self-completed questionnaire contained items about exposure to the following risk factors: tobacco; alcohol; diet; frequency of dental visits and familial cancer. Results and conclusions: this is the largest UK epidemiological study so far to be undertaken on young subjects diagnosed with oral cancer. One-hundred and sixteen cases were recruited representing a response rate of 59%. Slightly over 90% of this cohort were classified as white European. A large proportion of cases (40%) were from social classes I & II suggesting either a true social class difference in young cases versus older oral cancer cases or a possible bias in responders or survivors. Risk factors of tobacco use and excessive alcohol consumption were present in the majority (75%) of patients. Significant differences in the pattern of alcohol consumption were found in female subjects, who were less likely to consume over the recommended amounts of alcohol compared with male subjects. Daily regular fresh fruit and vegetable consumption during the ten year period before cancer diagnosis was recorded to be low. There was a distinct subgroup of cases, 26% of the group, that showed little, if any, exposure to any major risk factors.No Full Tex

Mutations of the cell cycle arrest gene p21WAF1, but not the metastasis-inducing gene S100A4, are frequent in oral squamous cell carcinomas from Sudanese toombak dippers and non-snuff-dippers from the Sudan, Scandinavia, USA and UK

PCR and direct DNA sequencing methods were used to analyse the prevalence of mutations in exon 2 of the p21waf1 gene in 14 oral squamous cell carcinomas (OSCCs) and 8 non-malignant oral mucosal lesions from Sudanese toombak dippers. For comparison, OSCCs (14 from the Sudan, 16 from Norway, 11 from Sweden, 21 from the USA and 14 from the UK) and non-malignant oral mucosal lesions (3 from the Sudan) from non-snuff-dippers were included. The prevalence of mutations in exons 2 & 3 of the S100A4 gene were analysed in the 14 OSCCs from toombak-dippers and in 25 cases of OSCCs from the control non-snuff-dippers. Of the 14 OSCCs investigated from toombak-dippers, mutations in the p21waf1 exon 2 were found in 43% (6 out of 14), compared to 14% (2 out of 14), 22% (6 out of 27) and 14% (5 out of 35) found in those from non-snuff-dippers from the Sudan, Scandinavia and the USA/UK, respectively. OSCCs from toombak-dippers showed 13 different mutations distributed as 10 (77%) transitions and 3 (23%) transversions. OSCCs from non-snuff-dippers from the Sudan, Scandinavia, the USA and the UK showed 33 different mutations distributed as 14 (42%) transitions and 19 (58%) transversions. In the OSCCs examined, cases with mutations in the p21waf1 also had p53 gene mutations. Only exon 2 of the S100A4 gene was found mutated in 3 cases of OSCCs (one from a toombak-dipper and two from the non-snuff-dippers). The toombak-dipper OSCC had 4 mutations (one transition, 3 transversions), compared to the OSCCs from non-snuff-dippers which showed 3 mutations each (one transition, 2 transversions). All these 3 cases were negative for mutations in the p21waf1 and p53 genes. No mutations of p21waf1 or S100A4 were found in the non-malignant oral mucosal lesions from the snuff-dippers/non-dippers. These findings suggest that; (i) p21waf1, together with p53, is a target gene of oral carcinogenesis in OSCCs from toombak-dippers, with the tobacco specific nitrosamines present in toombak possibly acting as principal carcinogens in these OSCCs; (ii) findings of p21waf1 exon 2 mutations in the OSCCs unrelated to snuff use further demonstrate that this gene may play an important role during the pathogenesis of OSCCs caused by smoked tobacco use; (iii) mutations in the S100A4 gene are rare in OSCCs, but appears to be complementary to p21waf1 and p53 mutations. Since molecular analysis of OSCCs can provide clues to endogenous or environmental factors contributing to the high risk of OSCCs, further analysis of the role of the p21waf1 gene mutations as a biomarker of malignant transformation, which is linked to the p53 gene, is necessary, especially in habitual users of toombak from the Sudan.Full Tex

Meta-analysis of measures of performance reported in oral cancer and precancer screening studies

Objective To elicit a range of values for sensitivity, specificity and other measures of performance in screening for oral cancer and precancer.Method A literature search which included three databases was conducted. Strict inclusion criteria were applied, Values for sensitivity (Sn) and specificity (Sp), from seven investigations, were expressed as a receiver operator characteristic (ROC) curve. Meta-analysis of the combined results was used to produce a summary operator characteristic (SROC) curve.Results The pooled weighted value of Sri from the seven studies was 0.796. From the SROC, the corresponding value of Sp at this level of Sri was 0.977 (95% Cl 0.941, 0.991). When So was held at 0.977, the corresponding value of Sn from the SROC was 0.796 (95% Cl 0.594, 0.912).Conclusions The reports selected for eventual inclusion revealed a high level of heterogeneity with respect to the location of investigations, prevalence of lesions, the personnel used and other factors. The meta-analysis indicated that overall the studies had high discriminatory ability. The estimates of Sri and So, and values obtained for other measures of screening performance, were considered suitable for input to 2 simulation model in assessing the likely cost-utility of a variety of screening scenarios in further planned research