Risk Factors For Oral Leukoplakia Research Articles

HPV frequency, p16 expression and risk factors for oral leukoplakia from Córdoba, Argentina

Background: Non-homogeneous results about the frequency of HPV in leukoplakia are presented in current literature, possibly linked to different factors. Among them, a diverse HPV geographical distribution was suggested. This study aimed to describe the frequency of HPV in patients diagnosed with leukoplakia. Patients & Methods: A cross-sectional study was carried out at the Facultad de Odontología, Universidad Nacional de Córdoba. HPV status was studied by polymerase-chain reaction (HPV-PCR) and p16 by immunohistochemistry. HPV status was analyzed concerning the clinical-demographic features using the Fisher test and the McNemar test. Results: There were included 33 patients diagnosed with different subtypes of oral leukoplakia. HPV genome was detected by PCR in 48.5% (n=16). The most common viral genotype was HPV16. p16 was positive in 27% (n=9) of the cases. The concordance between HPV detection techniques showed poor or weak agreement (Mc Nemar 0.1185). Except for chronic mechanical irritation with HPV-PCR + (p=0.0049), and tongue location with HPV-PCR + (p=0.0366), no significant statistical association between the other included variables was found. Conclusions: The low frequency of HPV in this study agrees with previous studies of our region. Chronic mechanical irritation could play a role in the development of HPV-associated leukoplakias, mainly located on the ventrolateral tongue.

Peroxiredoxin 1 inhibits autophagy through interacting with Rab7 in human dysplastic oral keratinocyte cells

ObjectiveAs a major risk factor for oral leukoplakia (OLK), oxidative stress can induce intracellular reactive oxygen species (ROS), which is closely related to autophagy. Ras-related protein 7 (Rab7) is an important molecule involved in autophagy. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, overexpressed in a variety of malignant tumors. We found that the expression of Prx1 in OLK was up-regulated, and Prx1 is associated with autophagy. This study aims to identify mechanisms of Prx1 in oxidative stress associated autophagy in human dysplastic oral keratinocyte (DOK) cells. DesignHydrogen peroxide (H2O2) was used to induce autophagy in DOK cells. CCK8 assay and flow cytometry were conducted to examine cell viability, cell apoptosis and intracellular ROS level. Autophagy-associated proteins were detected by western blot and immunofluorescence. MHY1485 was applied to investigate the role of Prx1 in autophagy. On the basis of online docking tool Zdock, Prx1 interacting with Rab7 was verified by immunofluorescence double-staining, Duolink PLA, and Co-immunoprecipitation (Co-IP). ResultsH2O2 induced autophagy and ROS increase in DOK cells, and the expression of Prx1 increased gradually according to H2O2 concentration. Prx1 knockdown attenuated the inhibition of MHY1485 on the expressions of autophagy-related proteins and the ratio of LC3 II/LC3 I induced by H2O2. Moreover, Prx1 interacted with Rab7 in DOK cells. ConclusionsPrx1 was involved in the regulation of H2O2-induced autophagy in DOK cells partly by physically interacting with Rab7. Prx1 knockdown promoted autophagy maybe by releasing more Rab7 into the autophagy process.

Nicotine promotes the development of oral leukoplakia via regulating peroxiredoxin 1 and its binding proteins.

Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.

THE IMPORTANCE OF A LONGITUDINAL ORAL LEUKOPLAKIA PROGRAM

Leukoplakia is defined as white plaques of questionable risk, since other specific conditions and other oral potentially malignant disorders have been excluded. Leukoplakia malignant transformation rate ranges from 1% to 39%; especially those lesions that exhibit microscopic epithelial dysplasia. In these cases, an increased risk of progression to squamous cell carcinomas is observed. Objective: This study aims to analyze the statistics of the management and follow-up of patients with oral leukoplakia and to report a case of a malignant transformation of this lesion. Study Design: Longitudinal observational study. Results: During 6 years, 87 patients with current or previous oral leukoplakia were examined. In the moment of evaluation, 80.5% were smokers or had recently quit the smoking habit, 77% admitted to alcohol ingestion, and 50.6% had sun exposure. Of all the histopathological diagnoses, 12.6% were dysplastic. Malignant transformation was observed in 3 cases in different sites: the border of the tongue, the soft palate, and the floor of the mouth. Conclusion: Our results agree with global literature that smoking and alcohol ingestion are risk factors for oral leukoplakia. Furthermore, our study highlights the importance of regular monitoring of these patients because they can present with malignant transformation. This type of program also performs oral cancer screenings. Leukoplakia is defined as white plaques of questionable risk, since other specific conditions and other oral potentially malignant disorders have been excluded. Leukoplakia malignant transformation rate ranges from 1% to 39%; especially those lesions that exhibit microscopic epithelial dysplasia. In these cases, an increased risk of progression to squamous cell carcinomas is observed. Objective: This study aims to analyze the statistics of the management and follow-up of patients with oral leukoplakia and to report a case of a malignant transformation of this lesion. Study Design: Longitudinal observational study. Results: During 6 years, 87 patients with current or previous oral leukoplakia were examined. In the moment of evaluation, 80.5% were smokers or had recently quit the smoking habit, 77% admitted to alcohol ingestion, and 50.6% had sun exposure. Of all the histopathological diagnoses, 12.6% were dysplastic. Malignant transformation was observed in 3 cases in different sites: the border of the tongue, the soft palate, and the floor of the mouth. Conclusion: Our results agree with global literature that smoking and alcohol ingestion are risk factors for oral leukoplakia. Furthermore, our study highlights the importance of regular monitoring of these patients because they can present with malignant transformation. This type of program also performs oral cancer screenings.

Is toombak a risk factor for oral leukoplakia and oral squamous cell carcinoma ? A systematic review.

Toombak is a form of smokeless tobacco that is not well known in Western Society but is widely used by the Sudanese population and many others in the sub-Sahara region. However, unlike other smokeless tobacco products, information on the carcinogenic potential of toombak is scarce. The present review explored any potential epidemiological association between the use of toombak and oral leukoplakia and oral squamous cell carcinoma (OSCC). Databases including the Web of Science, SCOPUS, EMBASE and PubMed were searched for literature on the potential association between toombak and oral leukoplakia and OSCC. The search also included grey literature. The search period extended from 1990 to 2018. Following data mining, the study selection was conducted by two reviewers independently. Eight studies that satisfied the inclusion criteria were included. Based on these results, there was a threefoldto sevenfold increased risk of developing the oral leukoplakia and oral squamous cell carcinoma among toombak users compared with non-users. Based on the results of the systematic review, there is a strong epidemiological evidence to suggest toombak to be a major risk factor for both oral leukoplakia and OSCC. Further studies are necessary to evaluate the molecular pathway of toombak-induced oral carcinogenesis.

Oral leukoplakia, a precancerous lesion of squamous cell carcinoma, in patients with long-term pegylated liposomal doxorubicin treatment.

Pegylated liposomal doxorubicin (PLD) has a good safety profile, but long-term use has been associated with development of squamous cell carcinoma of the tongue and oral cavity (SCCTO) in some patients. The study objective was to estimate the prevalence of oral leukoplakia, a known precursor of SCCTO, in patients with ovarian cancer and long-term PLD use.After approval of the institutional review board, medical record of 114 patients who were treated with PLD at our institution between January 2010 and December 2016 were retrospectively reviewed. All those patients have been referred for routine monitoring of oral mucositis every time before administration by a dentist. The patient characteristics included in the evaluation were age, smoking and drinking habits, the PLD dose and schedule, and presence or absence of oral leukoplakia and SCCTO at each oral examination. The relationships of the incidence of oral leukoplakia and patient characteristics were analyzed.The median total PLD dose was 160 (range 40–1550) mg/m2. Oral leukoplakia was seen in 6 (5.3%) patients. The median PLD dose, at the time of oral leukoplakia diagnosis, was 685 (range 400–800) mg/m2. SCCTO was not found. Univariate analysis revealed that age, Brinkman index, and habitual drinking were not considered as risk factors for oral leukoplakia, and only total PLD dose (OR, 1.470; 95% CI, 1.19–1.91; P < .001) remained as a significant independent risk factor for oral leukoplakia. The ROC curve analysis indicated that the optimal cutoff value of the total PLD dose to predict development of oral leukoplakia was 400 mg/m2. The sensitivity was 100% and the specificity was 88.8%. No patient discontinued PLD because of oral leukoplakia or SCCTO.The 2 most important clinical observations were the occurrence of oral leukoplakia in patients with long-term PLD use and that the development of oral leukoplakia was related to a total cumulative dose ≥400 mg/m2. Routine oral surveillance is recommended, particularly when the cumulative total dose exceeds 400 mg/m2.

WITHDRAWN: Human papillomavirus 16 as a risk factor for oral leukoplakia: A meta-analysis

WITHDRAWN: Human papillomavirus 16 as a risk factor for oral leukoplakia: A meta-analysis

Elucidating risk factors for oral leukoplakia affecting gingivae in Japanese subjects

Background: Clinicopathological studies have revealed some distinct anatomical variations in the clinical presentation of oral leukoplakia (OL). Screening studies have shown that gingival leukoplakia (GL) to be more common among the Japanese. Objective: A hospital-based case-control study was undertaken among patients diagnosed with OL to compare clinico-pathological data between GL and OL affecting other sites (n-GL). Methods: One hundred fifty-one subjects attending four city hospitals in Japan diagnosed with OL were recruited to this study. OL was diagnosed by World Health Organization criteria. They were interviewed for risk factors, clinical presentations were charted and investigated by patch testing for allergy to dental materials and by biopsy for dysplasia. Results: Eighty-eight with GL and 63 with n-GL were included in the study. GL lesions were predominantly white (93%) though n-GL leukoplakia had red (speckled) foci in 26%. Eighty percent of GL were seen in association with prosthesis or restorations. There were no significant differences by age or in tobacco and alcohol use in the two groups. Metal allergy test was positive in 58% of the GL but was not significantly higher compared to the n-GL (41%). Histopathological features showed that inflammatory cell infiltrate was predominant in n-GL group ( p = 0.021). Higher dysplasia grades were also found in n-GL ( p = 0.018). During follow-up, nine oral cancers (14%) were detected in n-GL group and among GL cases four developed oral carcinomas (5%) ( p = 0.043). Cox hazard regression analysis revealed that after adjusting for age and sex, GL group was found to have a lower malignant risk, with a hazard ratio of 0.89 (95% CI: 0.51–1.04) when compared to n-GL. Conclusions: GL was more benign compared to n-GL in Japanese subjects, though risk factors appear similar. Further study is warranted to ascertain whether trauma may play an important role for hyperkeratinization of gingival tissues and possible evolution of GL to proliferative verrucous leukoplakia in later years.

OP228: Elucidating risk factors for oral leukoplakia affecting gingivae among a Japanese population

Purpose Population screening studies in Japanese have confirmed that oral leukoplakia (OL) affecting the gingivae (gingival leukoplakia: GL) is the most frequent location of OL. We investigated a cohort of patients with GL and their clinic-pathological features were compared with patients with OL affecting other sites (n-GL). Methods Among 204 subjects diagnosed with OL (GL:114, n-GL:90) during 09-11 in 4 city hospitals in Japan, 151(74%) subjects (GL:88, n-GL:63) (age: 64.4 ± 12.7) were recruited. OL was diagnosed by WHO criteria (Warnakulasuriya et al., J Oral Pathol Med, 2007). They were interviewed for risk factors and investigated by patch testing for dental materials, biopsy for dysplasia recording and detection of aldehyde dehydrogenase (ALDH2) polymorphism in saliva by Real-Time PCR for SNP genotyping (rs671) and screened for HPV-DNA by GP5+/6+PCR from paraffin-embedded tissues among selected subjects ( n = 31). Results There were no significant differences by age (mean ages: GL, 65.9; n-GL, 62.3) or in tobacco and alcohol use in the two groups. Eighty-one percent of GL were seen in association with prosthesis and 27% close to amalgam fillings. Metal allergy test was positive in 58% of the GL but was not significantly higher compared to the n-GL (41%). Higher dysplasia grades were found in n-GL ( P = 0.018). Alcohol intolerance (flush reaction) was higher in n-GL (73%) ( P = 0.035). The homozygous ALDH2∗2/2 and 2∗1/2, which work less efficiently in alcohol metabolism was higher in n-GL (55%) than in GL (41%). HPV-DNA was not detected in any of the samples. Conclusions GL had lower dysplasia scores compared to n-GL, but the risk factors appear similar. Oral leukoplakia in n-GL may be associated with aberrant oxidative pathway of alcohol metabolism in Japanese. There was no evidence to support a causal relationship between HPV-DNA detection and GL nor n-GL (Funded by Sasakawa GB Foundation).

Abstract 2580: Pharmacologic inhibition of cytochrome P450 1B1 attenuates the motility and proliferation of cultured human dysplastic oral leukoplakia cells.

Abstract Oral leukoplakia is a precancerous lesion that may progress to squamous cell carcinoma of the head and neck (HNSCC). The long latency period to invasive cancer provides an opportunity for intervention at the precancerous stage. The inability of surgical resection to prevent the recurrence of oral leukoplakia speaks clearly to the need to develop an efficacious regimen for the chemoprevention of this disease. Tobacco smoke constituents and ethanol, the major risk factors for oral leukoplakia and HNSCC, are metabolized by cytochrome P450 1B1 (CYP1B1) to form potentially carcinogenic species. Our previous data indicate that knockdown of CYP1B1 in human oral leukoplakia cells (MSK-Leuk1) by shRNA decreases cell motility and proliferation, relative to control cells overexpressing empty vector. Homoeriodictyol (HED), a flavonoid found in citrus fruits, is a selective inhibitor of CYP1B1 (IC50 0.24 μM). As a next step, we hypothesized that pharmacologic inhibition of CYP1B1 by HED would attenuate cell motility and proliferation in a manner similar to genetic knockdown. Because HED is commonly found in our diet, its toxicity is expected to be low, making it a promising agent for preventive or therapeutic intervention. The ability of HED to inhibit CYP1B1 activity in MSK-Leuk1 cells was established by incubating cells with either vehicle (0.01% ethanol) or HED (5-10 μM) for 72 hrs and quantifying 7-ethoxyresorufin o-deethylation (EROD), a measure of the activity of CYP1B1 and other enzymes of the CYP1 subfamily. HED decreased EROD activity in a dose-dependent manner, with 40% inhibition observed at 10 μM, as compared to vehicle-treated controls. Western blot analyses revealed that CYP1B1 levels were unaltered following HED treatment. The effect of CYP1B1 inhibition on cell motility was examined by exposing MSK-Leuk1 cells to HED (0-10 μM) for 96 hrs followed by a wound-healing assay, in which the ability of cell monolayers to close a gap was monitored for 23 hrs. HED inhibited cell motility in a concentration dependent manner, with maximum inhibition of gap closure reached at 10 μM (6.7 fold relative to vehicle). To assess the effect of CYP1B1 inhibition on cell growth, MSK-Leuk1 cells were exposed to HED (0-10 μM) for 5 days and proliferation was analyzed (Fluorescent DNA Quantitation kit). A direct association was observed between HED dose and inhibition of proliferation, with a 33% decrease observed at 10 μM. In summary, inhibition of CYP1B1 activity by HED resulted in attenuation of the motility and proliferation of cultured MSK-Leuk1 cells. These data confirm that CYP1B1 is a promising molecular target for intervention in HNSCC and provide strong support for the further development of CYP1B1 inhibitors as efficacious agents for the prevention of HNSCC in patients with oral leukoplakia. (Supported by NCI fellowship 1 F32 CA144199-01). Citation Format: Ekaterina G. Shatalova, Margie L. Clapper. Pharmacologic inhibition of cytochrome P450 1B1 attenuates the motility and proliferation of cultured human dysplastic oral leukoplakia cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2580. doi:10.1158/1538-7445.AM2013-2580

Oral Leukoplakia as It Relates to HPV Infection: A Review.

Leukoplakia is the most common potentially malignant lesion of the oral cavity and can be categorised according to its clinical appearance as homogeneous or nonhomogenous. Tobacco and areca nut use, either alone or in combination are the most common risk factors for oral leukoplakia, but some oral leukoplakias are idiopathic. Some leukoplakias arise within fields of precancerized oral epithelium in which the keratinocytes may be at different stages of cytogenetic transformation. Leukoplakias may unpredictably regress, may remain stable, or may progress to carcinoma. There is a greater risk of carcinomatous transformation of idiopathic leukoplakia, of non-homogenous leukoplakia, of leukoplakia affecting the floor of the mouth; the ventrolateral surface of the tongue and the maxillary retromolar and adjoining soft palate (collectively called high-risk sites), of leukoplakia with high-grade epithelial dysplasia, and of leukoplakia in which the keratinocytes carry cytogenetic alterations associated with carcinomatous transformation. Although there appears to be some link between human papillomavirus (HPV) and oral leukoplakia, there is little evidence to support a causal relationship either between HPV infection and oral leukoplakia or between HPV-infected leukoplakic keratinocytes and their carcinomatous transformation.

Association between different alcoholic beverages and leukoplakia among non- to moderate-drinking adults: A matched case–control study

While heavy drinking is a risk factor for oral leukoplakia, the effects of moderate drinking and of different alcoholic beverages are unclear and were investigated in this case-control study. 187 leukoplakia patients, aged 40-65 years, who were not heavy drinkers and did not change their drinking/smoking habits over the last decade, were age/gender matched to 187 controls. The effect of regular, moderate, overall alcohol, beer, wine, spirit drinking, adjusted for the effects of heavy smoking and other important co-variables, were assessed using conditional logistic regression analysis. Overall alcohol (OR, 0.22), wine (OR, 0.20), spirits (OR, 2.93) were significantly associated to leukoplakia. A statistically significant interaction wine/heavy smoking was also found. Such different effects could be explained by the ethanol antagonising potential of other drink components, such as polyphenols, abundant in red wine and scarce in spirits. Among heavy smokers, the preventive effect of wine was more than multiplicative.

Need to Educate Primary Caregivers About the Risk Factor Profile of Smokeless Tobacco Users

Many cancer risk factors are correlated with one another, and the presence of 1 risk factor may be a marker for other unhealthy behaviors. In this article, we focus on smokeless tobacco (ST), a known risk factor for oral leukoplakia and oral cancer, and the cancer risk factors associated with its use. We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) I and the 1982-1984 NHANES I Epidemiologic Follow-up Study. Risk factor information was available on individuals 25-74 years of age, most of whom would be middle age or elderly today. Older subjects, Black males, and those living in the Southern Unite States had the highest prevalence of ST use. ST use was associated with current smoking (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.5), former smoking (OR, 1.6; 95% CI, 1.4-2.0), low fruit and vegetable intake, low SES, increased alcohol consumption (among nonsmoking ST users), and increased body mass index, all of which elevate cancer risk. CONCLUSION. Physicians and dentists should ask their patients about current or former ST use. Identification of ST users should prompt the physician or dentist to inquire about other chronic disease risk factors that the patient may have and to educate the ST using patient about ways to reduce their risk of cancer.

Assessment of risk factors for oral leukoplakia in West Virginia

To assess risk factors associated with oral leukoplakia in a US population with high use of smoked tobacco and smokeless tobacco. The RJ Gorlin Leukoplakia Tissue Registry was used to identify individuals with oral leukoplakia in West Virginia, USA. This case-control study consisted of 90 cases with oral leukoplakia and 78 controls with periapical cysts. Univariate-univariable (one dependent variable and one independent variable) and univariate-multivariable (one dependent variable and multiple independent variables) logistic regression modeling quantified the association between oral leukoplakia and potential explanatory variables. Unadjusted measures of association indicate that those with oral leukoplakia were more likely to be older [odds ratio of crude: OR(Crude) = 2.72; 95% confidence interval (CI): 1.45-5.11], more likely to currently use smokeless tobacco (OR(Crude) = 3.16; 95% CI: 1.10-9.07), and more likely to currently use snuff (OR(Crude) = 8.32; 95% CI: 1.83-37.80). Individuals currently using smokeless tobacco or currently using snuff were more likely to have oral leukoplakia [adjusted odds ratio, OR(Adj) = 9.21 and 30.08; 95% CI: 1.49-57.00 and 2.67-338.48, respectively], after simultaneously adjusting for age, gender, currently using smoked tobacco, currently using alcohol daily, and dental prostheses use. Generalizability is an issue when studying risk factors associated with oral leukoplakia because of geographical variations in the composition of smokeless tobacco (i.e. betel, lime, ash, and N-nitrosamines) and cultural variations in the use of tobacco (i.e. reverse smoking). Snuff was the main smokeless tobacco product currently used in West Virginia, and was strongly associated with oral leukoplakia, after adjusting for potential explanatory variables.

Cigarette smoking as a risk factor associated with oral leukoplakia

BACKGROUND: It is well known that oral leukoplakia is the most common precancerous lesion of the oral mucosa. Although tobacco and alcohol are known to be major risk factors for oral leukoplakia worldwide, there are no data on risk factors for oral leukoplakia in our country. The aim of our study was to analyze the association between oral leukoplakia and smoking habit, with attention to the duration and quantity of smoking. METHODS: The study population consisted of 352 patients aged 40-70 years. Prior to the clinical examination, each subject answered a standardized questionnaire regarding tobacco-smoking habits. Oral leukoplakia was diagnosed and grouped according to internationally accepted criteria. Chisquare test was used for statistical analysis. RESULTS: Of the entire sample, 279 were smokers and 73 non-smokers. Oral leukoplaka was found in 53 subjects and among them 50 were smokers and 3 were nonsmokers. All smokers had only used cigarettes. The relative risk of developing oral leukoplakia increased with duration of cigarette smoking habit. The majority of smokers with leukoplakia (74.0%) smoked more than 20 cigarettes per day compared to 34.5% of those without leukoplakia. The highest prevalence of leukoplakia (33.3%) was found in subjects who used cigarettes and alcohol. CONCLUSION: In view of these results, cigarette smoking is significantly related to the etiology of oral leukoplakia.

Alcohol drinking, body mass index and the risk of oral leukoplakia in an Indian population

Although tobacco habits have been associated with the risk of oral leukoplakia, alcohol drinking and body mass index (BMI) as risk factors have not been well established. The purpose of this study is to evaluate the independent effects of drinking, BMI, tobacco chewing and smoking on the risk of oral leukoplakia. A case-control study was conducted, with data from an ongoing randomized oral cancer screening trial in Kerala, India. Trained health workers conducted interviews and performed oral visual inspections to identify oral premalignant lesions such as leukoplakia. The logistic regression model in SAS was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 927 leukoplakia cases and 47,773 controls were included in the analysis. Ever alcohol drinking was a significant risk factor for oral leukoplakia among nonsmokers (OR=2.1, 95%CI=1.3, 3.4) and non-chewers (OR=1.8, 95%CI=1.3, 2.5) after adjusting for age, sex, education, BMI and tobacco habits. The association with alcohol drinking was stronger among women (OR=3.9, 95%CI=1.5, 10.4) than men (OR=1.5, 95%CI=1.3, 1.9). An inverse dose-response relationship was observed between BMI and the risk of oral leukoplakia (p for trend=0.0075). Tobacco chewing was a stronger risk factor for women (OR=37.7, 95%CI=24.2, 58.7) than for men (OR=3.4, 95%CI=2.8, 4.1). Smoking was a slightly stronger risk factor for men (OR=3.3, 95%CI=2.5, 4.3) than for women (OR=2.0, 95%CI=1.5, 2.9). In conclusion, alcohol drinking was found to be an independent risk factor while BMI might be inversely associated with the risk of oral leukoplakia in an Indian population. Int. J. Cancer 88:129–134, 2000. © 2000 Wiley-Liss, Inc.

Alcohol drinking, body mass index and the risk of oral leukoplakia in an Indian population

Although tobacco habits have been associated with the risk of oral leukoplakia, alcohol drinking and body mass index (BMI) as risk factors have not been well established. The purpose of this study is to evaluate the independent effects of drinking, BMI, tobacco chewing and smoking on the risk of oral leukoplakia. A case-control study was conducted, with data from an ongoing randomized oral cancer screening trial in Kerala, India. Trained health workers conducted interviews and performed oral visual inspections to identify oral premalignant lesions such as leukoplakia. The logistic regression model in SAS was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 927 leukoplakia cases and 47,773 controls were included in the analysis. Ever alcohol drinking was a significant risk factor for oral leukoplakia among nonsmokers (OR=2.1, 95%CI=1.3, 3.4) and non-chewers (OR=1.8, 95%CI=1. 3, 2.5) after adjusting for age, sex, education, BMI and tobacco habits. The association with alcohol drinking was stronger among women (OR=3.9, 95%CI=1.5, 10.4) than men (OR=1.5, 95%CI=1.3, 1.9). An inverse dose-response relationship was observed between BMI and the risk of oral leukoplakia (p for trend=0.0075). Tobacco chewing was a stronger risk factor for women (OR=37.7, 95%CI=24.2, 58.7) than for men (OR=3.4, 95%CI=2.8, 4.1). Smoking was a slightly stronger risk factor for men (OR=3.3, 95%CI=2.5, 4.3) than for women (OR=2.0, 95%CI=1.5, 2.9). In conclusion, alcohol drinking was found to be an independent risk factor while BMI might be inversely associated with the risk of oral leukoplakia in an Indian population.

Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers.

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.

Nass use, cigarette smoking, alcohol consumption and risk of oral and oesophageal precancer.

In a cross sectional study, conducted in Uzbekistan, an area with a high incidence of oral and oesophageal cancer, 1569 men were interviewed regarding use of nass quid, cigarette smoking and alcohol drinking. All subjects in the study had an oral examination, and oesophagoscopy was performed in 1344 men. Nass use and cigarette smoking emerged as independent risk factors for oral leukoplakia. The prevalence odds ratio (OR) for life-time nass intake equivalent rose from 1.0 in never-users to 5.17 [95% confidence interval (CI), 3.10-8.61] in the highest category; for total pack-years of cigarettes smoked the risk rose from 1.0 in never-smokers to 10.03 (95% CI, 4.9-20.6) in the highest category. There was a significant trend in risk (P < 0.001), for both factors. In the group with oral leukoplakia, the effect of nass use and cigarette smoking appeared to be additive. Cigarette smoking was also found to be an independent risk factor for oesophageal lesions and was significantly associated with chronic oesophagitis. The risk of chronic oesophagitis in the group with the highest pack-years of cigarettes smoked was approximately double that among non-smokers [Odds ratio (OR) = 2.47; 95% CI 1.34-4.56]. There was a weak association between nass use and oesophageal pathology: the highest life-time intake equivalent was associated with an OR of 1.56 (95% CI 1.09-2.23). Alcohol intake was not found to be independently associated with the presence of oral and oesophageal precancerous lesions.