Polymorphisms in the apoptosis‐associated genes FAS and FASL and risk of oral cancer and malignant potential of oral premalignant lesions in a Taiwanese population

J Oral Pathol Med (2010) 39: 155–161 Background: Our aim was to measure the relationship of FAS (?1377G>A and ?670A>G), FASL (?844C>T) gene variants and risk of oral cancer. Methods: Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) analysis was used to determine the FAS and FASL polymorphisms in 294 oral squamous cell carcinoma (OSCC), 53 oral submucous fibrosis (OSF), and 84 oral leukoplakia (OL) patients, as well as in 333 healthy controls. A standardized questionnaire was applied to collect demographic data, and potential confounding factors. JMP statistical software was used to analyze the association. Results: FAS and FASL polymorphisms were not correlated with OSCC development or the malignant potential of OL by simple and multivariate logistic regression. However, a two‐ to fourfold difference in the risks of betel quid chewing, alcohol consumption, and smoking on OSCC development were observed between participants with different FAS polymorphisms. FAS polymorphisms were significantly correlated with the malignant potential of OSF. Multivariate logistic regression analysis indicated that FAS A_?1377‐G_?670 vs. G_?1377‐A_?670 haplotype (OR = 2.26, 95% CI = 1.16–4.41) was correlated with the malignant potential of OSF. Conclusions: We suggest that FAS and FASL polymorphisms are not significantly correlated with OSCC development or malignant potential of OL. The impact of substance usage on OSCC development could be differentiated by FAS polymorphisms. FAS A_?1377‐G_?670 haplotype may play a role in the malignant potential of OSF.     

Risk of oral cancer associated with human papillomavirus infection, betel quid chewing, and cigarette smoking in Taiwan — an integrated molecular and epidemiological study of 58 cases

BACKGROUND: The association between oral squamous cell carcinoma (OSCC) and human papillomavirus (HPV) 6, 11, 16 and 18 is uncertain. Past reports varied in the methodology and results. We conducted this study using in situ PCR in situ hybridization (ISH) assay which was considered as the most sensitive method for detection of viral DNA. We undertook an epidemiologic survey about the history of betel quid chewing and cigarette smoking, since these habits are common in Taiwan. METHODS: In situ PCR ISH was performed on the tumor specimens from 29 patients with OSCC and the oral mucosal specimens from 29 patients without OSCC. Their betel quid chewing and cigarette smoking histories were also reviewed. RESULTS: HPV16, HPV18, betel quid chewing and cigarette smoking were statistically significant risk factors in univariate analysis. HPV6 and 11 were not. Multivariate analysis showed that HPV16 infection (adjusted Odds ratio = 11.20) and betel quid chewing (adjusted Odds ratio = 17.06) remained to be independent factors for OSCC. CONCLUSIONS: Our results showed that HPV16 and betel quid chewing were two major risk factors for OSCC in Taiwan, indicating that they act through different mechanisms in the pathogenesis of OSCC.     

Quantification of betel quid chewing and cigarette smoking in oral cancer patients

Background: Betel quid chewing and cigarette smoking are two of the risk factors for some dental diseases as well as oral cavity cancer in Taiwan. The aim of the study was to quantify these factors in oral cavity cancer patients and compare the prevalence of these factors in patients and the general population. Methods: A questionnaire was designed to evaluate betel quid chewing, cigarette smoking and alcohol drinking in 254 patients, who had squamous cell carcinoma of the oral cavity, and had received surgical excision at the Changhua Christian Hospital in Taiwan between 2005 and 2008. The results were compared with those of population of Taiwan, based on a nation‐wide survey with sample of 26 744 people. Results: We found that more than 80% of the male patients were both betel quid chewers and smokers. Few women in the survey practiced betel quid chewing, cigarette smoking or alcohol drinking. Chewers and smokers usually started the habits in their 20s. On average, a chewer patient consumed 12 508 betel quid pieces per year, for 23.3 years before the diagnosis of oral cavity cancer, making the total amount of betel quid consumed nearly 310 000 pieces; and a smoker patient consumed 469 packs per year, for 28.5 years before diagnosis, making the total number of about 14 000 packs. Patients with both habits had the age at diagnosis 4 years earlier than the smoker‐only patients, 5 years earlier than the chewer‐only patients, and 6 years earlier than those with neither. Conclusions: On average, it took two decades of betel quid chewing and cigarette smoking before oral cavity cancer diagnosis, making the life‐time consumption of these substances an astonishing amount. Betel quid chewing and cigarette smoking patients are more likely to be diagnosed with oral cavity cancer at a younger age than those who have just one habit or none. Patients that smoke more are not only more likely to be diagnosed at a younger age, but also at an advanced stage.     

Functional variants of IL4 and IL6 genes and risk of tobacco-related oral carcinoma in high-risk Asian Indians

Oral Diseases (2011) 17 , 720–726 Background: Tobacco‐related oral squamous cell carcinoma (OSCC) is one of the most common cancers involving Indian males. We assessed the association of IL4 promoter –589 T>C, –33 T>C, and IL6–174 G>C functional genetic polymorphisms with tobacco‐related OSCC in Asian Indians. Patients and Methods: The IL4 and IL6 promoter polymorphisms were assessed in 140 patients with OSCC and 120 normal subjects by PCR–RFLP technique, and significance of the data was determined using chi‐square test. Results: The frequency of TC, CC genotype, and C allele at IL4 promoter sites –589 and –33 were higher in patients when compared with controls. Consequently, TC/CC genotypes and C allele at both sites appeared as susceptible. However, IL6–174 G>C single‐nucleotide polymorphisms (SNP) appeared to be protective in patients with OSCC. Of eight haplotypes, five were associated with two‐ to seven‐fold increased risk of tobacco‐related OSCC. These SNPs further showed heterogeneity among different ethnic population, but their distribution in Asian Indians stand closer to other Asian populations. Conclusions: In this study, IL4–589 CC, –33 CC genotype, and *C allele at both sites appeared to be susceptible, while IL6–174 CC genotype and *C allele appeared to be protective in patients with OSCC; hence, these SNPs may be a potential prognostic markers for tobacco‐related OSCC in Asian Indians.     

Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan

A hospital-based case-control study of matched pairs was conducted to explore (a) the relationship between the use of betel quid chewing, cigarette smoking, alcohol drinking and oral cancer and (b) synergism between these factors. The case group consisted of 104 male and 3 female oral cancer patients and these were compared with 194 male and 6 female matched controls. We found by univariate analysis that alcohol consumption, smoking, betel quid chewing, educational level and occupation were associated with oral cancer. The adjusted odds ratios were to be found elevated in patients who were smoking and betel quid chewing. After adjusting for education and occupation covariates, the incidence of oral cancer was computed to be 123-fold higher in patients who smoked, drank alcohol and chewed betel quid than in obstainers. The synergistic effects of alcohol, tobacco smoke and betel quid in oral cancer were clearly demonstrated, but there was a statistically significant association between oral cancer and betel quid chewing alone. Swallowing betel quid juice (saliva extract of betel quid produced by chewing) or including unripened betel fruit in the quid both seemed to enhance the risks of contracting oral cancer.     

Survivin SNP-carcinogen interactions in oral cancer

In Taiwan, oral cancer is causally associated with environmental carcinogens. Survivin is an anti-apoptotic protein and is generally considered a marker of malignancy. The current study explored the combined effect of survivin gene polymorphisms and environmental carcinogens on the risk and clinico-pathological development of oral cancer. Five single-nucleotide polymorphisms (SNPs) of survivin genes from 439 male patients with oral cancer and 424 male control participants (who did not have cancer) were analyzed. The survivin -31GG, +9194 GG, and +9809 TT homozygotes exhibited higher risk for oral cancer compared with the corresponding ancestral genotype, after adjustment for related confounders. The survivin -31, +9194, and +9809 SNPs combined with betel quid chewing and/or tobacco consumption could robustly elevate susceptibility to oral cancer. The distribution frequency of the -31 G: +9194 A: +9809 T haplotype was significantly higher in oral cancer patients than in control participants. These results suggest that survivin gene polymorphisms and their interactions with environmental carcinogens may increase susceptibility to oral cancer in Taiwanese men. Abbreviations: AOR, adjusted odds ratio; CI, confidence intervals; PCR, polymerase chain-reaction; SNP, single-nucleotide polymorphisms.     

School-level contextual factors associated with betel quid chewing among schoolchildren in Taiwan

Abstract – Objectives: Previous to this research, no literature had explored the clustering of betel quid chewing at the school‐level and the contextual factors contributing to this behavior among elementary schoolchildren. This study therefore examines this in clusters stratified according to school geography and the rate of aboriginal students in each school. Individual‐level characteristics are controlled in the study. Methods: The data used derive from student and parent surveys of the School Smoking Survey Project from a sampling of third and fourth grade children from 13 elementary schools in Tao‐Yuan County, Taiwan (n = 1585). The individual‐ and school‐level characteristics regarding betel quid chewing were estimated using multi‐level logistic regression analysis. Results: Compared to their counterparts, students attending schools with higher percentages of aboriginal students (OR = 3.60, 95% CI: 1.31–9.95), or those schools located in a mountainous region (OR = 2.82, 95% CI: 1.19–6.70), were found to have a greater risk of chewing behavior. Other observed characteristics having a significant relationship to student chewing behavior were drinking alcohol and smoking cigarettes. Conclusions: The new findings from this study suggest that the specific school attended is an important point of intervention. Therefore, effective policies and preventive programs should be strongly considered for implementation in schools that are putting students at the greatest risk for betel quid chewing behavior. Our study also confirmed the relationship between betel quid chewing, cigarette smoking, and alcohol drinking, suggesting that multifaceted intervention strategies need to be considered in regard to such behaviors among elementary schoolchildren.     

Oral cancer in Myanmar: a preliminary survey based on hospital‐based cancer registries

J Oral Pathol Med (2011) 40 : 20–26 The occurrence of oral cancer is not clearly known in Myanmar, where betel quid chewing habits are widely spread. Since betel quid chewing has been considered to be one of the important causative factors for oral cancer, the circumstantial situation for oral cancer should be investigated in this country. We surveyed oral cancer cases as well as whole body cancers from two cancer registries from Yangon and Mandalay cities, both of which have representative referral hospitals in Myanmar, and we showed that oral cancer stood at the 6th position in males and 10th in females, contributing to 3.5% of whole body cancers. There was a male predominance with a ratio of 2.1:1. Their most frequent site was the tongue, followed by the palate, which was different from that in other countries with betel quid chewing habits. About 90% of male and 44% of female patients had habitual backgrounds of chewing and smoking for more than 15 years. The results revealed for the first time reliable oral cancer frequencies in Myanmar, suggesting that longstanding chewing and smoking habits are etiological backgrounds for oral cancer patients.     

A quantitative evaluation of the aetiological role of betel quid in oral carcinogenesis

Computer aided search and review of bibliographies of published papers and monographs revealed 17 case control studies of oral cancer and betel quid chewing from 1933 to 1990. Studies were assessed and site specific risk of oral cancer associated with chewing betel quid with and without tobacco in the quid among smokers and non-smokers was computed. Tobacco smoking and chewing betel quid containing tobacco arose as important risk factors for oral cancer, betel quid without tobacco significantly increased risk in only one study. Heterogeneity in estimates of risk among studies was reduced by restricting analysis to those with more exact definition of exposure and site of the cancer. Variation in risk among studies reflects bias in selection and inadequate definition of exposure and tumour site and an inability to control effectively for confounding. Further studies, addressing these issues are advised, to clarify the role of betel quid without tobacco as a carcinogen, alone and in combination with tobacco smoke.     

The effect of betel quid and cigarette on multistate progression of oral pre-malignancy

Background:  Although the effect of betel quid chewing and smoking on oral cancer has been well documented, both influences, dose and duration during life time, on multistate progression of oral pre-malignancy are hardly addressed.
Methods:  By recruiting a group of male chewers from different occupation groups, we modeled the effects of both duration and quantity of betel quid chewing and smoking on annual incidence rate of developing leukoplakia and average dwelling times (ADTs) staying in leukoplakia and erythroleukoplakia.
Results:  The annual incidence rate (per year) of leukoplakia was estimated as 0.35% (95% CI: 0.22–0.48%). The ADTs were 24 years for leukoplakia and 7 years for erythroleukoplakia. Annual incidence rate of leukoplakia with high consumption and long duration of betel quid and smoking was higher. Both quantity and duration of smoking and betel quid chewing play minor roles in the influence of ADT. The risks of developing oral cancer after 20 years of follow-up were 42.2% for leukoplakia and 95.0% for erythroleukoplakia.
Conclusion:  The effects of betel quid chewing and smoking on multistate progressions between oral pre-malignancies were elucidated. These results can be applied to predict long-term risk of malignant transformation varying with different duration and quantity of betel quid and cigarette.     

Relationship between betel quid additives and established periodontitis among Bangladeshi subjects

Aim: To determine the relationship between betel quid chewing additives and established periodontitis in Bangladeshi subjects. Material and Methods: A total of 864 subjects participated in this study. Among them, 140 pairs of sex‐ and age‐matched case subjects and control subjects were selected. A case was defined as a person who had at least two sites with a clinical attachment level (CAL)6 mm and at least one site with probing depth (PD)5 mm. Subjects who did not fulfill these criteria were considered as controls. Information on sociodemographic variables, psychological stress, dental health behaviour, smoking and betel quid chewing habits was obtained. Results: Multiple logistic regression analysis showed that current betel quid chewers had greater probabilities of having established periodontal disease than did non‐chewers (odds ratio=3.97, p<0.05). Mean PD, mean CAL, mean percentage of bleeding on probing and number of missing teeth were significantly higher in chewers of betel quid with tobacco and masala than in chewers of betel quid without such additives adjusting for age, sex, smoking habit, body mass index, dental visit pattern, stress and plaque index. Higher frequency and longer duration of betel quid chewing showed a significant relation to an increase in periodontal parameters. Conclusion: The results indicate that betel quid additives might significantly enhance periodontitis in the population studied.     

Hypoxia inducible factor‐1α expression in areca quid chewing‐associated oral squamous cell carcinomas

Oral Diseases (2010) 16 , 696–701 Objectives: Hypoxia inducible factor (HIF)‐1α gene expression is mainly induced by tissue hypoxia. Overexpression of HIF‐1α has been demonstrated in a variety of cancers. The aim of this study was to compare HIF‐1α expression in normal human oral epithelium and areca quid chewing‐associated oral squamous cell carcinoma (OSCC) and further to explore the potential mechanisms that may lead to induce HIF‐1α expression. Methods: Twenty‐five OSCC from areca quid chewing‐associated OSCC and 10 normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line GNM cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N‐acetyl‐l ‐cysteine (NAC), AP‐1 inhibitor curcumin, extracellular signal‐regulated protein kinase inhibitor PD98059, and protein kinase C inhibitor staurosporine were added to find the possible regulatory mechanisms. Results: Hypoxia inducible factor‐1α expression was significantly higher in OSCC specimens than normal specimen (P < 0.05). Arecoline was found to elevate HIF‐1α expression in a dose‐ and time‐dependent manner (P < 0.05). The addition of NAC, curcumin, PD98059, and staurosporine markedly inhibited the arecoline‐induced HIF‐1α expression (P < 0.05). Conclusions: Hypoxia inducible factor‐1α expression is significantly upregulated in areca quid chewing‐associated OSCC and HIF‐1α expression induced by arecoline is downregulated by NAC, curcumin, PD98059, and staurosporine.     

Heat shock protein 47 expression in oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells

J Oral Pathol Med (2010) 40 : 390–396 Background: Heat shock protein 47 (HSP47) is a product of CBP2 gene located at chromosome 11q13.5, a region frequently amplified in human cancers. Areca quid chewing is a major risk factor of oral squamous cell carcinoma (OSCC). The aim of this study was to compare HSP47 expression in normal human oral epithelium and OSCC and further to explore the potential mechanisms that may lead to induce HSP47 expression. Methods: Thirty‐two OSCC specimens and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line OC2 cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N‐acetyl‐l ‐cysteine (NAC), extracellular signal‐regulated protein kinase (ERK) inhibitor PD98059, phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002, cyclooxygenase‐2 inhibitor NS‐398, and tyrosine kinase inhibitor herbimycin A were added to find the possible regulatory mechanisms. Results: HSP47 expression was significantly higher in OSCC specimens than normal epithelium (P < 0.05). No significant difference in HSP47 expression was observed with respect to age, sex, T category, stage, and differentiation (P > 0.05). The lower HSP47 expression was associated with lymph node metastasis (P = 0.015). Arecoline was found to elevate HSP47 expression in a dose‐ and time‐dependent manner (P < 0.05). The addition of NAC, PD98059, LY294002, NS398, and herbimycin A markedly inhibited the arecoline‐induced HSP47 expression (P < 0.05). Conclusion: Our findings demonstrated that HSP47 expression is significantly upregulated in areca quid chewing‐associated OSCCs. HSP47 could be used clinically as a marker for lymph node metastasis of oral carcinogenesis. In addition, arecoline‐induced HSP47 expression was downregulated by NAC, PD98059, LY294002, NS398, and herbimycin A.     

Khmer dental and medical students' knowledge about the betel quid chewing habit in Cambodia

95 of 144 questionnaires submitted by volunteer Khmer medical and dental students on the betel quid chewing habit in Cambodia were evaluated (58 medical, 37 dental). Questions related to the composition of the betel quid, the physiological and oral effects as well as traditional and sociological aspects. Statistical tests showed that there were differences between dental and medical students, particularly relating to the knowledge about oral effects. While 81.1% of dental students knew that betel quid chewing causes oral cancer, only 31.0% of the medical students were adequately informed. Similarly, 51.4% of the dental students knew about the relation between betel quid chewing and submucous fibrosis compared to 8.6% of the medical students (P < 0.001). In contrast, only 18.9% of the dental students thought that betel quid chewing strengthens the gum, while 56.9% of the medical students believed that betel quid chewing would have this effect (P < 0.001). The answers also showed that students do not indulge in the betel quid habit. The decline of the betel quid chewing habit was also indicated by the fact that while 5.3% of students had parents chewing betel quid, in contrast 40% of students reported grandparents with this habit. There are deficiencies of knowledge about the most important effects of betel quid chewing, particularly in medical students. Since both medical and dental students will in their future professional life have an enormous impact on health and health education, it seems justified that the dental and medical curricula should focus on these traditional habits. Proper health education starting in the dental and medical school is warranted in Cambodia and probably also in other South and Southeast Asian countries where the betel quid chewing habit is prevalent so as ultimately to improve public knowledge on the oral and other effects of this habit.     

Comparing dose–response measurements of oral habits on oral leukoplakia and oral submucous fibrosis from a community screening program

J Oral Pathol Med (2010) 39 : 306–312 Background: Many studies have reported that the interaction and dose–response effects of betel quid chewing, tobacco smoking and alcohol drinking habits are important risk factors for oral cancer and precancerous lesions or conditions. These results are useful for comparing statistics, but may not be informative for personal disease‐related information. Methods: This study used data from a community screening program to evaluate the dose–response effects of daily frequency and duration from oral habits in Taiwan. The receiver operating characteristic (ROC) curves were further used to compare exposure measurements on indicating the occurrence of lesions/conditions. Results: Our results showed that the highest prevalence was found in leukoplakia (11.1%) and followed by oral submucous fibrosis (OSF, 4.4%). Betel quid chewing habit was found to have dose–response effects on leukoplakia and OSF, cigarette smoking habit only has the dose–response effect on leukoplakia, and alcohol drinking was not associated with both oral precancers. The daily frequency of chewing habit is a better indicator than other dose–response measurements for the occurrence of precancers. In addition, the cut‐off points of two to five counts per day have about 60–82% of sensitivities and 79–88% of specificities. Conclusions: The cut‐off points from ROC curves can provide an informative message to people with oral habits and their chances of developing diseases. High daily frequency of chewing can lead to excessive irritation to oral mucosa. Although the tobacco is never added to chewing quid in Taiwan, intensive irritation may play an important role in developing oral precancers in Taiwan.     

Single nucleotide polymorphisms of the vascular endothelial growth factor gene associated with incidence of oral squamous cell carcinoma

J Oral Pathol Med (2010) 39 : 786–792 Background: Vascular endothelial growth factor (VEGF) plays an important role in promoting angiogenesis and is overexpressed in several malignancies. Polymorphisms of the VEGF gene can alter VEGF protein expression, which may be biologically significant and account for heterogeneity in disease risk and outcome. The aim of this case–control study was to evaluate potential associations between single nucleotide polymorphisms (SNP) of the VEGF gene with susceptibility of oral squamous cell carcinoma (OSCC). Patients and methods: Five VEGF SNP (?1154 G/A, +405 G/C, +936 C/T, ?2578 C/A and ?460 C/T) were determined in peripheral blood isolated from 80 patients with OSCC and from 40 age‐ and gender‐matched healthy volunteers (RT‐PCR). Results: The +936 T allele and the ?2578 C/A SNP were expressed significantly more often in the OSCC‐group (P = 0.002; P < 0.0001) where three associations between two SNPs (+936 and +405, ?2578 and ?1154, ?460 and ?2578) were found. Conclusion: Our findings provide support that +936 T allele and ?2578 C/A SNP of the VEGF gene alone or in combination with other SNP are associated with OSCC. The SNPs may be used as biomarker for the development of specialized anti‐VEGF drugs. Further studies must confirm the value of preoperative genetic analysis for prognosis.     

Oral Candida carriage,quantification, and species characterization in oral submucous fibrosis patients and healthy individuals

Aim: To determine the prevalence of oral Candida carriage, candidal quantification, and various subtypes of Candida species in oral submucous fibrosis patients and healthy individuals. Methods: The study comprised 30 clinically‐diagnosed and ‐staged oral submucous fibrosis patients aged 20–40 years, and 20 age‐ and sex‐matched controls. Buccal mucosa was sampled by sterile swab technique. Each sample was inoculated on Sabouraud’s dextrose agar and CHROMagar culture media. Candida species identification was done using the KB006 Candida identification kit. Results: Eleven (36.67%) cases in the study group, and two (10%) cases in the control group, yielded Candida on culture. The value of CFU/mL increased with an increased duration of betel quid chewing habit. All Candida‐positive oral submucous fibrosis patients complained of a burning sensation. Candida albicans and Candida tropicalis were the most common species in the oral submucous fibrosis cases. Candida dubliniensis was isolated in both the study and control groups. Conclusions: Our observations in this study affirm that oral submucous fibrosis favors the colonization of Candida. Mucosal alterations due to the underlying disease process or betel quid chewing, coupled with other factors, might lead to candidal colonization, even in the absence of clinically‐related mycotic manifestations.     

The effects of chewing areca/betel quid with and without cigarette smoking on oral submucous fibrosis and oral mucosal lesions

OBJECTIVES: The purpose of this study was to investigate the risk of areca/betel quid chewing with or without cigarette smoking on oral submucous fibrosis (OSF) and other oral mucosal lesions. METHODS: A stratified case-control study was designed. There were in total 102 patients with oral mucosal lesions or OSF (confirmed pathologically) in the case group. OSF (n = 62) and oral mucosal lesions (n = 62) in 102 subjects were separately analyzed for men and women investigating their risks. RESULTS: For OSF, people with both smoking and chewing habits had a statistically significant odds ratio (OR) 8.68 (95% CI = 1.87, 40.23). For the group of people with chewing habit only and without any lifetime cigarette smoking habit, the OR was 4.51 (95% CI = 1.20, 16.94). For other oral mucosal lesions, people with mixed habits and chewing only had also significant risks (OR = 8.37 and 3.95, respectively). For both OSF and other oral lesions, the ORs of mixed habits and chewing only were both higher in women than in men. Conclusions: The areca/betel quid used in Taiwan does not contain any tobacco product. The only way of areca/betel quid could synergize with any tobacco product is through cigarette smoking. A statistically significant association with oral mucosal lesions and OSF was still found in the group of areca/betel quid chewing only.     

Epidemiological survey of oral submucous fibrosis and leukoplakia in aborigines of Taiwan

A population-based survey was designed to investigate the prevalence of areca/betel quid chewing, oral submucous fibrosis and leukoplakia in a typical aboriginal community of southern Taiwan. Three hundred and twelve people 20 years of age or older were collected in the study. The prevalence of chewing areca/betel quid was 69.5%, with an average of 17.3 portions a day for an average 24.4 years. More women (78.7%) than men (60.6%) chewed areca/betel quid. The prevalences of oral submucous fibrosis and leukoplakia were 17.6% and 24.4%, respectively. It was found that the odds ratio for chewing areca/betel quid and having at least one of the above oral mucosal lesions was 8.21. Any additional smoking or drinking habits were not significant for having oral mucosal lesions. Although the areca/betel quid in Taiwan does not contain any tobacco, a significant association was still identified between areca/betel quid chewing and oral mucosal lesions.     

A case-control study of oral cancer in Changhua County, Taiwan

Forty oral cancer patients identified consecutively in Changhua Christian Hospital between 1990 and 1992 were compared with 160 population-based controls, matched for sex, age, area of residence, and educational background. Betel quid chewing was positively associated with the risk of oral cancer with an adjusted odds ratio of 58.4 (95% CI: 7.6–447.6). The greater the number of years of chewing betel quid, the higher the risk of oral cancer; the adjusted odds rations were 12.9, 93.7 and 397.5 for <21, 21–40, and >40 years of betel chewing as compared with the non-users. The risk also increased with the quantity chewed per day; the odds ratios for those chewing <10, 10–20 and >20 quids/day were 26.4, 51.2 and 275.6, respectively. These odds ratio estimates were all statistically significantly different from the null value of unity.