Chewing tobacco, alcohol, and the risk of erythroplakia. (1/7)

Although chewing tobacco, smoking, and alcohol drinking have been suggested as risk factors for oral cancer, no study has examined the relationship between those factors and the risk of erythroplakia, an uncommon but severe oral premalignant lesion. In this study, we have analyzed the effects of chewing tobacco, smoking, alcohol drinking, body mass index, and vegetable, fruit, and vitamin/iron intake on the risk of erythroplakia and explored potential interactions between those factors in an Indian population. A case-control study including 100 erythroplakia cases and 47,773 controls was conducted, as part of an on-going randomized oral cancer screening trial in Kerala, India. The analysis was based on the data from the baseline screening for the intervention group, where the diagnostic information was available. The information on epidemiological risk factors was collected with interviews conducted by trained health workers. The erythroplakia cases were identified by health workers with oral visual inspections, and then confirmed by dentists and oncologists who made the final diagnosis. The odds ratios (OR) and their 95% confidence intervals (CIs) were calculated by the logistic regression model using SAS software. The adjusted OR for erythroplakia was 19.8 (95% CI, 9.8-40.0) for individuals who had ever chewed tobacco, after controlling for age, sex, education, body mass index, smoking, and drinking. The adjusted OR for ever-alcohol-drinkers was 3.0 (95% CI, 1.6-5.7) after controlling for age, sex, education, body mass index, chewing tobacco, and smoking. For ever-smokers, the adjusted OR was 1.6 (95% CI, 0.9-2.9). A more than additive interaction on the risk of erythroplakia was suggested between tobacco chewing and low vegetable intake, whereas a more than multiplicative interaction was indicated between alcohol drinking and low vegetable intake, and between drinking and low fruit intake. We concluded that tobacco chewing and alcohol drinking are strong risk factors for erythroplakia in the Indian population. Because the CIs of interaction terms were wide and overlapping with those of the main effects, only potential interactions are suggested.  (+info)

Erythroplasia of queyrat: coinfection with cutaneous carcinogenic human papillomavirus type 8 and genital papillomaviruses in a carcinoma in situ. (2/7)

Erythroplasia of Queyrat is a carcinoma in situ that mainly occurs on the glans penis, the prepuce, or the urethral meatus of elderly males. Up to 30% progress to squamous cell carcinoma. The cause of erythroplasia of Queyrat is largely unknown. Human papillomavirus type 16 DNA has previously been detected only in very few distinctly characterized patients. We have investigated 12 paraffin-embedded biopsies from eight patients with penile erythroplasia of Queyrat and control biopsies of inflammatory penile lesions, of genital Bowen's disease, and of premalignant/malignant cervical or vulvar lesions by 10 different polymerase chain reaction protocols for the presence of cutaneous and genital/mucosal human papillomaviruses. Human papillomavirus typing was performed by sequencing (cloned) polymerase chain reaction products. Human papillomavirus DNA was detected in all erythroplasia of Queyrat patients and in none of the controls with inflammatory penile lesions. The rare cutaneous carcinogenic epidermodysplasia verruciformis-associated human papillomavirus type 8 was present in all erythroplasia of Queyrat patients and the genital high-risk human papillomavirus type 16 in seven of eight patients (88%). In addition to human papillomavirus type 8 and human papillomavirus type 16, four patients carried the genital carcinogenic human papillomavirus type 39 and/or type 51. All human papillomavirus type 8 sequences found in erythroplasia of Queyrat showed some polymorphism among each other and differed in specific nucleotide exchanges from the human papillomavirus type 8 reference sequence. Viral load determinations (human papillomavirus copies/beta-globin gene copies) by realtime polymerase chain reactions showed that the human papillomavirus type 16 levels in the erythroplasia of Queyrat biopsies were one to five orders of magnitude higher than the human papillomavirus type 8 levels. Human papillomavirus type 8 was not detected in cervical or vulvar precancerous and cancerous lesions and in Bowen's disease lesions that carried genital human papillomavirus types. The data suggest that in erythroplasia of Queyrat, in contrast to other genital neoplasias, a coinfection with human papillomavirus type 8 and carcinogenic genital human papillomavirus types occurs. The presence or absence of human papillomavirus type 8 might help to distinguish between penile erythroplasia of Queyrat and Bowen's diseases.  (+info)

Gross genomic aberrations in precancers: clinical implications of a long-term follow-up study in oral erythroplakias. (3/7)

PURPOSE: Gross genomic aberrations are increasingly seen as a cause rather than a consequence of carcinogenesis. Carcinomas may be prevented by systemically acting agents when used in high-risk individuals. If gross genomic aberrations could be shown to be predictive markers in precancers, they could serve as a tool for identifying high-risk individuals to be included in chemopreventive trials. PATIENTS AND METHODS: To investigate the predictive power of gross genomic aberrations in several types of oral premalignancies, we analyzed 57 biopsies from oral erythroplakias of 37 patients, both histologically and for DNA content. DNA content was measured by high-resolution image cytometry, and distribution histograms of DNA content were generated and interpreted according to established protocols. The primary end point was cancer-free survival. RESULTS: Fifty-seven dysplastic oral red lesions from 37 patients were investigated. Forty-one lesions from 25 patients were classified with aberrant DNA content (DNA aneuploidy), of which 23 patients (92%) later developed an oral carcinoma (after a median observation time of 53 months; range, 29 to 79 months). Of 12 patients having altogether 16 lesions with normal DNA content, none developed a carcinoma (median observation time, 98 months; range, 23 to 163 months; P <.001). In multivariate analysis, DNA content was a significant prognostic factor (P <.001), whereas histologic grade, sex, use of tobacco, size and location of lesions, and the presence multiple of lesions were not. CONCLUSION: Gross genomic aberrations are highly predictive for the subsequent occurrence of carcinomas from a wide range of oral premalignancies.  (+info)

Chromosome instability in lymphocytes: a potential indicator of predisposition to oral premalignant lesions. (4/7)

Oral premalignant lesions (OPLs) are related to tobacco use and mark individuals at high risk for oral cancer development. Increased mutagen sensitivity as measured by an in vitro mutagen challenge assay has been shown to be a risk factor for upper aerodigestive tract cancers. In this case control study, we used two assays with mutagens relevant to tobacco exposure (benzo[a]pyrene diol epoxide (BPDE) and bleomycin) to see whether sensitivity to these mutagens could be used as biomarkers for assessing risk of premalignant lesions. Furthermore, we evaluated whether 3p21.3 is a molecular target of BPDE damage in lymphocytes of patients with OPLs. There were 82 patients with OPLs and 89 healthy controls frequency matched to the cases on age, sex, ethnicity, and smoking status. These subjects' lymphocytes were treated in two separate experiments with either 2 microM BPDE for 24 h or 0.03 units/ml bleomycin for 5 h, and the frequency of induced chromatid breakage in Giemsa-stained preparations was determined. BPDE-induced 3p21.3 aberrations were scored by fluorescent in situ hybridization technique in 1000 interphases/sample. We found that the mean BPDE-induced chromatid breaks per cell were higher in cases than controls (1.05 +/- 0.40 and 0.55 +/- 0.27, respectively; P < 0.01). Similar results were evident with bleomycin-induced chromatid breaks per cell (0.78 +/- 0.37 and 0.57 +/- 0.31, respectively; P < 0.01). After adjusting for age, sex, ethnicity, and smoking status, significantly elevated odds ratios (95% confidence interval) for OPL risk were noted for BPDE sensitivity [12.96 (5.51, 30.46)] and bleomycin sensitivity [3.33 (1.64, 6.77)]. When subjects were categorized into quartiles of the number of breaks per cell, a dose response was observed for both assays. The adjusted odds ratios for subjects with increasing numbers of breaks per cell in quartiles were 2.34, 9.14, and 54.04 for BPDE sensitivity and 1.92, 3.33, and 7.15 for bleomycin sensitivity, respectively. Subjects sensitive to both mutagens had a 50-fold increased risk for OPLs. In addition, there were significantly more BPDE-induced chromosome aberrations at the 3p21.3 locus in cases (51.13/1000) than in controls (40.93/1000; P < 0.0001). However, no such difference was observed for 3q13, a control locus. BPDE-induced 3p21.3 aberrations were associated with an elevated risk for OPLs of 6.08 (2.57, 14.4). The degree of BPDE sensitivity at 3p21.3 and risk for OPLs increased in a dose-dependent manner. In summary, BDPE sensitivity and bleomycin sensitivity appear to be individually and jointly associated with elevated risk of OPLs. Furthermore, 3p21.3 may be a molecular target of BPDE in OPLs. This is the first study to examine mutagen sensitivity in a premalignant condition. The next step is to correlate these findings in surrogate (lymphocyte) tissue with molecular events in the target tissue.  (+info)

Advances in the diagnosis of oral premalignant and malignant lesions. (5/7)

The diagnosis and treatment of oral premalignant lesions and squamous cell carcinoma are currently based on histopathologic features, site of involvement and stage of disease. Recent advances in techniques for detecting lesions and predicting their progression or recurrence are reviewed here. Adjuncts for detection of lesions and selection of biopsy sites include vital tissue staining (with toluidine blue) and exfoliative cytology. Advances in diagnosis and staging at the molecular level are expected to affect choice of treatment and patient outcomes. Oral health care providers should be aware of these advances in the evaluation and diagnosis of oral premalignant lesions and squamous cell carcinoma.  (+info)

Oral erythroplakia and speckled leukoplakia: retrospective analysis of 13 cases. (6/7)

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Frequent gene deletions in potentially malignant oral lesions. (7/7)

Some oral cancers are preceded by premalignant lesions which include leucoplakia and erythroplakia. At present there are no reliable markers to identify lesions that may progress to malignancy. We have analysed 30 potentially malignant oral lesions for deletions at chromosomal regions that harbour tumour-suppressor genes for oral cancer. A total of 16 of 30 cases (53%) showed loss of heterozygosity (LOH) or allele imbalance at TP53, DCC, 3p21.3-22.1 or 3p12.1-13. These genetic alterations were detected in dysplastic lesions but not in histologically normal mucosa and may be early events in the carcinogenic process. A total of 64% of dysplastic lesions that recurred during the study showed LOH or allele imbalance in the initial biopsy and the number of genetic abnormalities increased in the tumours that developed. This type of molecular profiling may help to identify patients with lesions that may recur or acquire additional genetic events and progress to malignancy.  (+info)