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.     

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.     

Betel quid chewing,oral cancer and other oral mucosal diseases in Vietnam: a review

Background: Betel quid chewing (BQC) in Vietnam is still prevalent, however, no detailed information about its association with oral cancer and pre‐cancer are available in the English literature. Respective online searches (PubMed, Medline) were negative. Methods: Relevant publications in Vietnamese were collected by the authors and translated. Visits to cancer centres and institutes of odontology (Ho Chi Minh City, Hanoi) were made and seminars with respective scientists were held. Field excursions to local markets and interviews with betel quid vendors and individual BQ chewers gave further insights. Results: Generally, BQC is on the decline in Vietnam. 6.7% of the female population still seems to indulge in this habit. In an earlier study, a prevalence of 0.06% of oral cancer was reported. In a study of 1084 cases of oral cancer, the male:female ratio was 1.05:1 (1997). The age group between 60 and 75 years is most often affected by oral cancer. In BQ chewing women, the buccal mucosa (27.9%), tongue (23.1%) and lips (22.4%) are most often affected. Verrucous carcinoma is seen in the age group 70–79 years with women most often being affected (male:female ratio 1:3.4). The most important risk factor for oral cancer in women is BQC compared with men where smoking, alcohol drinking or combined smoking and drinking habits are the most common risk factors. Oral leukoplakia in BQ chewers is observed in 3.8%, oral submucous fibrosis in 13%. Conclusions: BQC in Vietnam is on the decline. Association between BQC and oral cancer in elderly women is still of importance. Eventually, the BQC habit will vanish and only play a role in socio‐ritual contexts.     

Infrequent p53 mutations in patients with areca quid chewing-associated oral squamous cell carcinomas in Taiwan

Mutations in the conserved regions (exons 5-9) of the p53 gene were investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing analyses. P53 mutations were detected in 2 of 37 (5.4%) oral SCC cases. One tumor sample (case 23) showed a mis-sense point mutation at codon 177, changing CCC to CTC, which resulted in a substitution of proline to leucine in the p53 protein. The other tumor (case 33) had a point mutation at codon 266, changing GGA to AGA and causing a substitution of glycine to arginine in the p53 protein. These two patients with p53 mutations did not have an areca quid chewing habit. These results suggest that mutations in the p53 gene may not play a role in the pathogenesis of human oral SCCs in Taiwan. Recently, we have shown that positive p53 staining was observed in 47 of 81 (58%) cases of oral SCC. The discrepancies between positive p53 protein staining and the low prevalence of p53 mutation in oral SCCs indicate that other mechanism(s) are involved in p53 overexpression.     

Expression of p53 protein correlates with decreased survival in patients with areca quid chewing and smoking-associated oral squamous cell carcinomas in Taiwan

Expression of p53 protein was examined in oral squamous cell carcinoma (SCC) from patients who were areca quid (AQ) chewers and/or tobacco smokers, using anti-p53 antibodies with an immunoperoxidase technique. Positive p53 stain was observed in 47 of 81 (58%) cases of oral SCC. p53 overexpression was found to higher in patients without AQ chewing and smoking habits than in patients with these two habits (80% vs 52%, P=0.076). No significant correlation was found between p53 expression and the patients' age, sex, cancer location, clinical staging, primary tumor TNM status, or histological differentiation of SCC. The Kaplan-Meier analysis showed that the prognosis for patients with p53-negative tumors was significantly better than that for patients with p53-positive tumors (P<0.05). A significant correlation was also observed between positive lymph node status and poor prognosis (P<0.05). These results suggest that p53 may serve as an adjuvant marker of poor survival in patients with oral SCCs in Taiwan.     

Precancerous and other oral mucosal lesions related to chewing, smoking and drinking habits in Thailand

In a field study (1979-1984) four out of six major hilltribes of Northern Thailand, namely the Lahu, Karen, Lisu and Meo, as well as a group of rural Thai, were examined. Chewing, smoking and drinking habits and lesions of the oral mucosa (leukoedema, preleukoplakia, leukoplakia and chewer's mucosa) were recorded. 1866 individuals were examined. Considerable differences in the chewing and smoking habits among the various tribes were recorded and some of them were considered tribe-specific. Chewing of betel and miang was more prevalent among older people; these habits seem to have lost their attraction for the younger people. Cigarette smoking was more prevalent among middle-aged individuals. Leukoedema was observed in 12.4%, preleukoplakia in 1.8%, leukoplakia in 1.1% and chewer's mucosa in 13.1%. Men and the older generation were affected more often, except that more women (Karen and Thai) revealed chewer's mucosa. A positive correlation could be demonstrated between some mucosal lesions (leukoedema, chewer's mucosa) and some smoking and chewing habits.     

Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25-27, 1996

A variety of betel/areca nut/tobacco habits have been reviewed and categorized because of their possible causal association with oral cancer and various oral cancer and various oral precancerous lesions and conditions, and on account of their widespread occurrence in different parts of the world. At a recent workshop in Kuala Lumpur it was recommended that "quid" be defined as "a substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or any manufactured or processed form." Clear delineations on contents of the quid (areca nut quid, tobacco quid, and tobacco and areca nut quid) are recommended as absolute criteria with finer subdivisions to be added if necessary. The betel quid refers to any quid wrapped in betel leaf and is therefore a specific variety of quid. The workshop proposed that quid-related lesions should be categorized conceptually into two categories: first, those that are diffusely outlined and second, those localized at the site where a quid is regularly placed. Additional or expanded criteria and guidelines were proposed to define, describe or identify lesions such as chewer's mucosa, areca nut chewer's lesion, oral submucous fibrosis and other quid-related lesions. A new clinical entity, betel-quid lichenoid lesion, was also proposed to describe an oral lichen planus-like lesion associated with the betel quid habit.     

Prevalence and related risk factors of betel quid chewing by adolescent students in southern Taiwan

The prevalence and related risk factors of betel quid chewing among adolescent students were studied in a junior high school (group 1) and in a vocational school (group 2) in southern Taiwan. Group 1 consisted of 3548 participants (89.7% response rate) and group 2 of 1358 (97.6% response rate). The students were asked to complete a questionnaire anonymously. In the junior high school 1.9% of students including all grades (13-15 years old) and both sexes was found to be a current betel quid chewer and 14% was an ex-chewer, whereas 10.2% of vocational school students (16–18 years old) was a current chewer and 31% was an ex-chewer. The prevalence of betel chewing was significantly higher among boys than girls. A high proportion of chewers were also a smoker and alcohol drinker. A statistical analysis of sociodemographic factors showed that male students who smoked tobacco, consumed alcohol and were friends or classmates of students who were betel quid chewers, were the likeliest adolescents to chew betel quid.     

MDM2 expression in areca quid chewing-associated oral squamous cell carcinomas in Taiwan

MDM2 (murine double minute gene 2) overexpression has been implicated in the pathogenesis of human tumors via inhibition of the p53 tumor suppressor protein. To investigate the potential involvement of MDM2 overexpression in the pathogenesis of oral squamous cell carcinomas (SCCs) in Taiwan, we examined the expression of MDM2 protein and its relationship to p53 protein levels in 52 oral SCCs using antibodies to MDM2 and p53. Of the 52 patients, 36 (69 %) had tumors with positive MDM2 nuclear staining and 32 (61%) had tumors with p53 nuclear staining. Co-expression of MDM2 protein and p53 was detected in 25 (48%) cases; and 9 (17%) tumors showed neither MDM2 protein nor p53 staining. A significant correlation was observed between MDM2 protein and p53 expression in 38 cases with an areca quid (AQ) chewing habit (P=0.032). No significant correlation was found between the degree of MDM2 protein staining and the patients' ages, sex, cancer location, clinical staging, primary tumor TNM status or histological differentiation of SCC at the time of initial presentation. Kaplan-Meier analysis showed that either MDM2 protein expression or co-expression of p53 and MDM2 protein did not relate significantly to patient overall survival. Nevertheless, the high prevalence of MDM2 protein overexpression found in this study suggest that MDM2 may also participate in the carcinogenesis of AQ chewing-associated oral SCCs in Taiwan.     

Prognostic role of p21WAF1 expression in areca quid chewing and smoking-associated oral squamous cell carcinoma in Taiwan.

BACKGROUND: Alterations in p21WAF1 protein expression have been observed in a wide variety of human cancers by immunohistochemistry, and both decreased and increased levels of p21WAF1 protein expression have been shown to correlate with poor prognosis. METHOD: To examine the relation between p21WAF1 protein expression and prognosis in oral squamous cell carcinomas (SCCs), we performed an immunohistochemical study with antip21WAF1 antibody on 43 oral SCCs. Immunostaining results were then correlated with p53 protein levels, clinicopathological parameters of the tumors and overall patient survival. RESULTS: Of the 43 patients, 31 (72%) had tumors with positive p21WAF1 nuclear staining and 27 (63%) had tumors with p53 nuclear staining. There was no significant correlation between p21WAF1 and p53 protein expressions and both mutant p53-containing oral SCCs overexpressed p21WAF1 protein. In addition, no significant correlation was found between the p21WAF1 expression and the patients' age, sex, oral habit, cancer location, or primary tumor TNM status at the time of initial presentation. The Kaplan-Meier analysis showed a significant correlation between p21WAF1 protein overexpression and poor patient overall survival (P = 0.049). When p53 and p21WAF1 were evaluated together, the 5-year overall survival was lowest in p53(+)-p21WAF1(+) patients and highest in p53(-)-p21WAF1(-) patients (P = 0.057). CONCLUSION: Combined evaluation of p21WAF1 and p53 expressions may be useful in estimating the prognosis of patients with oral SCCs in Taiwan.     

Oral lichenoid contact lesions induced by areca nut and betel quid chewing: a mini review

Betel quid (BQ) and areca nut chewing is widely prevalent in many parts of Asia and Asian‐migrant communities throughout the world. Global reports estimate 600 million users. Sufficient evidence of carcinogenicity has been found for BQ and its main ingredient, areca nut. BQ areca nut users have an increased risk of potentially malignant disorders. Among chewers, BQ remains in contact with the oral mucosa for prolonged periods. This review examines the clinical and pathological aspects of lichenoid lesions caused by areca nut and BQ, a condition that has received little attention in the published literature.     

Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing

Oral submucous fibrosis (OSF) is a high risk precancerous condition, predominantly affecting Indians. Consumption of chilli was hypothesized as an etiologic factor on the basis of ecological observations and a solitary animal experimental study. Subsequent epidemiologic studies that included case-series reports, large cross-sectional surveys, case-control studies, cohort and intervention studies have identified areca nut as the major etiologic agent. Tissue-culture studies involving human fibroblasts, areca nut extracts and areca nut alkaloids supported this etiologic hypothesis by showing fibroblastic proliferation and increased collagen formation. Currently, the role of genetic susceptibility and that of autoimmunity are receiving attention. The influence of nutritional factors, if any, remains unclear.     

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.     

Pilot survey of oral mucosa in areca (betel) nut chewers on Hainan Island of the People''s Republic of China

100 people on Hainan Island were studied for their smoking and chewing habits and the condition of their oral mucosa. Ninety-five percent of the study population chewed areca (betel) nut. In men this habit was supplemented with either smoking cigarettes or water pipe. In two men a small commissural leukoplakia was found. In three women clinical and histologic changes pointed towards oral submucous fibrosis.     

875例口腔黏膜鳞癌患者吸烟、饮酒、咀嚼槟榔情况的回顾性分析

目的 初步反映吸烟、饮酒、咀嚼槟榔与口腔黏膜鳞癌发病情况的关系。方法 查阅湖南地区12家大型三甲医院2004—2008年间口腔黏膜鳞癌病例资料,详细了解其发病前吸烟、饮酒、咀嚼槟榔情况并加以分析。结果 本研究中日吸烟量在1~20支占绝大多数(70.5%),吸烟年限在20年以上占68.5%,吸烟指数在400支×年以上占73.1%;日饮酒量在5两及以下占54.7%,饮酒年限在20年以上占62.1%,饮酒者口底部位构成比有所增高(P<0.05);槟榔咀嚼者发病部位构成比变化大(P<0.05),尤以颊、舌最为明显;31~50岁年龄段构成比明显增高(P<0.05),平均年龄48.6岁,而非槟榔咀嚼者平均年龄56.0岁;同时有吸烟、饮酒、咀嚼槟榔习惯者平均年龄50.3岁。结论 吸烟、饮酒、咀嚼槟榔对口腔黏膜鳞癌发病都有一定的影响。     

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.     

Betel‐quid and oral submucous fibrosis: a cross‐sectional study in Hunan province,China

J Oral Pathol Med (2012) 41 : 748–754 Background: The development of betel‐quid (BQ) processing industry in Hunan has increased the usage of this substance and may produce significant health consequences. However, the update data for the prevalence of BQ chewing and its effect on oral submucous fibrosis (OSF) are limited. Methods: A population‐based survey was conducted to investigate the prevalence of BQ chewing and OSF in Hunan. A questionnaire interview and an oral examination were conducted. A multivariate logistic regression model was used to study the effect of socio‐demographic characteristics on area‐specific behaviors of BQ chewing. Results: A total of 2356 subjects participated in this survey, with a 78.5% of response rate. The lifetime prevalence of BQ chewing was 16.2% (2.9% for ex‐chewers and 13.3% for current‐chewers). The findings from multivariate logistic regression model showed that a higher prevalence of this habit was among individuals who were males, urban residents, 15–49 years old, educated for 9–12 years, smokers, and drinkers. Male chewers occupied a fairly higher percentage of the combined use of tobacco and/or alcohol (86.1–87.5%) than the non‐chewers (50.6–56.7%). The overall prevalence of OSF was 1.0%. Compared with the subjects without OSF (1.7–23.2%), a significantly higher proportion of OSF patients were a current‐chewer (62.3% in men and 100.0% in women). Conclusions: BQ chewing is a vital risk factor for OSF in Hunan. A high prevalence of BQ chewing found among the younger cohort (15–49 years old) is an urgent warning for this oral premalignant disorder.     

Epidemiologic study of 6000 villagers of oral precancerous lesions in Bilugyun: preliminary report

Abstract A house-to-house survey of 11 villages selected by random sampling was carried out in Bilugyun, Chaung-zone township, Mon State of South Eastern Burma to study the prevalence of oral precancerous lesions and smoking and chewing. A total of 6000 villagers who were above 15 years at the time of this study were examined. The prevalence of preleukoplakia was 0.3%, leukoplakia 1.7%, lichen planus 0.4%, leukokeratosis nicotina palati 2.3, erythroplakia 0.1%, submucous fibrosis 0.1 %, and cancer 0.03%. A correlation was done between habits and lesions.     

Lycopene: features and potential significance in the oral cancer and precancerous lesions

J Oral Pathol Med (2010) 40 : 361–368 Data from epidemiological studies have indicated that diets rich in fruits and vegetables are likely to benefit many aspects of the prevention of oral malignancy. Lycopene is a red‐coloured carotenoid predominantly accumulated in tomatoes as well as other fruits and vegetables. It has been claimed to alleviate chronic diseases such as cancers and cardiovascular disease. Hence, the aim of this review is to summarize the features and its potential significance of lycopene in the development, prevention and treatment of oral premalignant lesions and oral cancer. Studies showed that lycopene might have beneficial effects in the management of some premalignant lesions in the oral cavity including oral submucous fibrosis and oral leukoplakia and may be an adjunct in the prevention and therapy of oral cancer. However, more mechanistic studies and randomized controlled trials of large sample size are necessary to further confirm these effects and to eventually make lycopene to be used in the community prevention and clinically routine management of these diseases.     

Prevalence of betel quid chewing habit in Taiwan and related sociodemographic factors

The prevalence of betel quid chewing habit in Taiwan was surveyed in a group of Chinese people from Kaohsiung city and in a second group from the aboriginal inhabitants of South Taiwan. In all 1299 participants constituted Group 1 (85.2% response rate) and 827 Group 2 (70.1% response rate). People were interviewed in their homes in house-to-house survey, according to a structured questionnaire developed and evaluated by the authors. Of the Kaohsiung inhabitants covering all ages and both sexes, 6% was a current betel chewer and 4% was an ex-chewer, whereas 42% of the aborigines aged over 15 yr was a current chewer and 1% an ex-chewer. Lifetime prevalence was 10%. Betel chewing enjoys islandwide popularity among the 20 million inhabitants of Taiwan; the number of current and ex-users was estimated at 2.0 million (95% CI 1.6-2.4 million). The betel quid was prepared in two different ways. In one, used mainly by aborigines, fresh areca nut was simply wrapped with betel leaf and in another, popular mainly among Chinese, a lengthwise piece of betel fruit and lime paste was sandwiched between two halves of an areca nut. A high proportion of chewers was also a smoker and drinker, but tobacco was not found to be chewed together with betel quid. Consumption varied between 14 to 23 portions per day, with individual frequencies ranging widely from 1 to over 200 portions a day. A statistical analysis of sociodemographic factors showed that lesser educated older men, blue collar workers, smokers and drinkers were the likeliest betel chewers.