Betel quid not containing tobacco and oral leukoplakia: a report on a cross-sectional study in Papua New Guinea and a meta-analysis of current evidence

Leukoplakia is an asymptomatic, potentially malignant change in the oral mucosa. Previous studies have reported that smoking and betel quid chewing are associated with increased risk of leukoplakia; few studies have reported on these associations in populations where betel quid does not contain tobacco. We conducted a case-control study nested in a cross-sectional study in Papua New Guinea and a systematic review of studies that included chewers of betel quid without tobacco. Our study recruited 1,670 adults. We recorded betel quid chewing and smoking. The prevalence of leukoplakia was 11.7%. In the nested case-control study of 197 cases and 1,282 controls, current betel chewing was associated with increased risk of leukoplakia with an adjusted odds ratio for current chewers of 3.8 (95% CI 1.7, 8.4) and in the heaviest chewers of 4.1 (95% CI 1.8, 9.1) compared to non-chewers. Current smoking was associated with an increased risk of leukoplakia with an adjusted odds ratio for current smokers of 6.4 (95% CI 4.1, 9.9) and amongst heaviest smokers of 9.8 (95% CI 5.9, 16.4) compared to non-smokers. The systematic review identified 5 studies examining risk of leukoplakia associated with betel quid chewing in populations where betel quid did not contain tobacco and that controlled for smoking. In studies that adjusted for smoking, the combined random effect odds ratio was 7.9 (95% CI 4.3, 14.6) in betel quid chewers. The results of this study and systematic review of similar studies provide evidence of the role of betel quid not containing tobacco and leukoplakia.     

Impact of betel quid, tobacco and alcohol on three-stage disease natural history of oral leukoplakia and cancer: implication for prevention of oral cancer.

The natural history of the three-stage process from normal, oral leukoplakia to oral cancer in relation to betel quid chewing, smoking and drinking is rarely addressed. The aim of this study was to simultaneously quantify the effects of three risk factors on occurrence of oral leukoplakia and malignant transformation to oral cancer. A hospital-based case-control study design derived from three retrospective cohorts from 1988 to 1998 was conducted. A total of 74 oral cancer patients, 164 patients with oral leukoplakia and 187 controls were interviewed to collect information on their betel chewing, smoking and drinking habits. The effects of the three risk factors on the progression rates of the three-stage disease process were estimated using the three-state Markov model. Subjects who chewed betel quid were at greater risk of leukoplakia (adjusted odds ratio (OR) 17.7 (9.03-34.5)) but there was no significant effect on malignant transformation (OR 1.04 (0.61-1.76)). Smoking played a major role in the onset of leukoplakia (OR 4.26 (2.21-8.23)) but a minor role in malignant transformation (OR 1.36 (0.69-2.68)). Alcohol was positively associated with malignant transformation (OR 2.37 (1.47-3.82)) but unrelated to occurrence of leukoplakia (OR 0.76 (0.04-1.43)). We concluded that smoking and betel quid were two significant risk factors for the occurrence of leukoplakia, whereas alcohol was significantly responsible for malignant transformation.     

Betel quid not containing tobacco and oral cancer: a report on a case-control study in Papua New Guinea and a meta-analysis of current evidence

Smoking and betel quid chewing are associated with increased risk of oral cancer but few studies have reported on associations in populations where betel quid does not contain tobacco. We conducted a case-control study in Papua New Guinea and a systematic review. Our case-control study recruited 143 cases with oral cancer and 477 controls. We collected information on smoking and betel quid chewing. Current smoking was associated with an increased risk of oral cancer with an adjusted odds ratio (OR) for daily smokers of 2.63 (95% confidence intervals (95% CI) 1.32, 5.22) and amongst heaviest smokers of 4.63 (95% CI 2.07, 10.36) compared to never-smokers. Betel chewing was associated with increased risk of oral cancer with an adjusted OR for current chewers of 2.03 (95% CI 1.01, 4.09) and in the heaviest chewers of 2.47 (95% CI 1.13, 5.40) compared to nonchewers. The OR in those who both smoked tobacco and chewed betel quid was 4.85 (95% 1.10, 22.25), relative to those who neither smoked nor chewed. The systematic review identified 10 previous studies that examined risk of oral cancer associated with betel quid chewing that controlled for smoking in populations where betel quid did not contain tobacco. In studies that reported results for non-smokers the combined OR was 2.14 (95% CI 1.06, 4.32) in betel quid chewers and in studies that adjusted for smoking the combined OR was 3.50 (95% CI 2.16, 5.65) in betel quid chewers. Preventive efforts should discourage betel quid chewing as well as smoking.     

Chewing areca nut, betel quid, oral snuff, cigarette smoking and the risk of oesophageal squamous-cell carcinoma in South Asians: a multicentre case-control study

Oesophageal cancer remains an important public health problem worldwide. This multicentre matched case-control study examined the chewing areca nut alone, betel quid with tobacco, oral snuff (snuff dipping) and cigarette smoking as the risk factors for oesophageal squamous-cell carcinoma. We enrolled 91 cases of oesophageal squamous-cell carcinoma and 364 matched controls from three tertiary-care hospitals in Karachi, Pakistan. A structured questionnaire was used to collect the data through face-to-face interview of the participants. Multivariable conditional logistic regression model showed that after adjusting for the effect of ethnicity, ever chewed areca nut alone (adjusted matched odds ratio (mOR(adj))=3.7; 95% confidence interval (CI): 1.6-8.5), ever chewed betel quid with tobacco (mOR(adj)=12.8; 95% CI: 6.3-26.2), ever practiced snuff dipping (mOR(adj)=4.3; 95% CI: 1.6-11.7) and ever smoked cigarettes (mOR(adj)=2.9; 95% CI: 1.4-5.9) were significantly and independently associated with oesophageal squamous-cell carcinoma status. The adjusted summary population attributable risk (PAR) percent for all four substances together was 67.0. Furthermore, despite incomplete synergy, there was manifold increase in the risk of oesophageal squamous-cell carcinoma, if the respondents ever smoked cigarettes and ever chewed betel quid with tobacco (mOR(adj)=21.4; 95% CI: 6.3-72.4) or if they ever smoked cigarettes and ever practiced snuff dipping (mOR(adj)=14.4; 95% CI: 2.3-91.1). The adjusted PAR (%) was higher for the dual practice of smoking cigarettes and chewing betel quid with tobacco (64.3) than the dual practice of smoking cigarettes and snuff dipping (32.2). Public awareness to curtail the addiction to these substances may result in a substantial reduction in the incidence of oesophageal squamous-cell carcinoma and related mortality in this and similar settings.     

The precancer risk of betel quid chewing,tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan

In areas where the practise of betel quid chewing is widespread and the chewers also often smoke and drink alcohol, the relation between oral precancerous lesion and condition to the three habits is probably complex. To explore such association and their attributable effect on oral leukoplakia (OL) and oral submucous fibrosis (OSF), a gender-age-matched case-control study was conducted at Kaohsiung, southern Taiwan. This study included 219 patients with newly diagnosed and histologically confirmed OL or OSF, and 876 randomly selected community controls. All information was collected by a structured questionnaire through in-person interviews. A preponderance of younger patients had OSF, while a predominance of older patients had OL. Betel quid chewing was strongly associated with both these oral diseases, the attributable fraction of OL being 73.2% and of OSF 85.4%. While the heterogeneity in risk for areca nut chewing across the two diseases was not apparent, betel quid chewing patients with OSF experienced a higher risk at each exposure level of chewing duration, quantity and cumulative measure than those who had OL. Alcohol intake did not appear to be a risk factor. However, cigarette smoking had a significant contribution to the risk of OL, and modified the effect of chewing based on an additive interaction model. For the two oral premalignant diseases combined, 86.5% was attributable to chewing and smoking. Our results suggested that, although betel quid chewing was a major cause for both OL and OSF, its effect might be difference between the two diseases. Cigarette smoking has a modifying effect in the development of oral leukoplakia.     

Correlates of Betel Nut Chewing among Burmese Refugees in Nebraska

Background: Betel nut chewing is an important risk factor for oral cancer, yet there has been little research identifying correlates of betel nut chewing among Burmese refugees in the U.S. Methods: Based on survey data from 188 Burmese refugees from Nebraska between 2015 and 2016, logistic regression was estimated to identify correlates of betel nut chewing. Results: The prevalence rate of betel nut chewing among participating Burmese refugees in Nebraska was 29%. Relative to Burmese refugees who had an education of less than high school, refugees with higher education were less likely to report betel nut chewing (AOR=0.1, 95% CI (0.02, 0.61)). Refugees who worked full time had higher odds of chewing betel nuts compared to those otherwise (AOR=6.17, 95% CI (1.80, 21.10)). Delaying medication purchase due to cost during the past 12 months was associated with higher odds of betel nut chewing (AOR=5.20, 95% CI (1.02, 26.39)). Conclusions: Betel nut chewing was common among Burmese refugees in the U.S., yet the odds of betel nut chewing varied across different socioeconomic groups. Health education programs that aim to reduce betel nut chewing might become more cost-effective by disproportionately targeting and serving high-risk groups among Burmese refugees.     

Dose-response relationships of oral habits associated with the risk of oral pre-malignant lesions among men who chew betel quid

Betel quid, cigarettes and alcohol are well-recognized risk factors for oral cancer. However, the combined effect of the frequency and duration of these oral habits on the risk for developing oral pre-malignancies among betel quid users has not been fully addressed. In this study, an oral screening programme for men chewing betel quid was carried out by well-trained dentists for early detection of oral pre-malignancy lesions. Using generalized logit model and proportional odds model, we found that, compared with the occasional user, the adjusted odds ratios of developing leukoplakia for men chewing one to 10 pieces of betel quid, 11-20 pieces, and more than 20 pieces per day were estimated as 2.14 (95% confidence interval [CI] 1.62-2.81), 2.99 (95% CI 2.06-4.27), and 5.37 (95% CI 3.76-7.47), respectively. The corresponding figures for erythroleukoplakia were 3.69 (95% CI 1.55-8.79), 13.78 (95% CI 5.76-32.98), and 36.64 (95% CI 15.94-84.16), respectively. Similar results were found while the duration was considered. The dose-response relationships were not as noteworthy for cigarette and alcohol drinking.     

Different impact from betel quid, alcohol and cigarette: risk factors for pharyngeal and laryngeal cancer

The risks of betel quid chewing with or without tobacco, alcohol drinking and cigarette smoking have been well explored in the oral cavity but not in the pharynx and larynx. We conducted a case-control study to investigate the association of these three risk factors to cancers of the pharynx and larynx in Taiwan. A total cases of 148 pharyngeal cancer, 128 laryngeal cancer and 255 hospital controls, all men, were recruited. Betel quid chewing was a significant independent risk factor (adjusted odds ratio [aOR] = 7.7; 95% confidence interval [CI] = 4.1-15.0) similar to that of alcohol drinking (aOR = 6.6; 95% CI = 3.5-13.0) for pharyngeal cancer, but not for laryngeal cancer (aOR = 1.3; 95% CI = 0.7-2.5) on which cigarette smoking (aOR = 7.1) exerts a stronger significant independent risk than alcohol drinking (aOR = 3.8). For pharyngeal cancers, chewers who consumed >20 quid/day, chewed with inflorescence in the quid or swallowed the betel quid juice were at higher risks; significant dose-response effects were found in daily quantity of drinking and chewing, and cumulative quantity of drinking. Synergistic effects from the 3 risk factors existed both on the pharynx (aOR = 96.9) and the larynx (aOR = 40.3), and attributed for 93.1% and 92.9% respectively. Our study is the first evidence to show that betel quid chewing without tobacco has different impact on the pharynx (digestive tract) and the larynx (airway), and supports the concept that exposure quantity and direct mucosal contact with the betel quid juice may contribute to carcinogenesis. Our results show an important insight into the impact of betel quid chewing on other sites of the digestive tract other than the oral cavity.     

Association between metabolic syndrome and oral pre-malignancy: a community- and population-based study (KCIS No. 28)

To elucidate the effect of metabolic syndrome (MetS) on oral pre-malignancy (OPM) and also to examine whether the effect is independent of areca nut chewing. We enrolled a total of 79,940 subjects aged 20 years or older undergoing both oral mucous examination and health check-up for MetS within the Keelung Community-based Integrated Screening program between 2003 and 2008. We identified 368 leukoplakia, 72 erythroleukoplakia, and 69 oral submucous fibrosis. The multi-variable logistic regression was used to assess the association between MetS and OPM with adjustment of age, gender, areca nut chewing, smoking, and alcohol drinking. Subjects with MetS were at increased risk for OPM (adjusted odds ratio (aOR)=1.68, 95% confidence interval (CI): 1.39-2.04) compared with those without MetS after taking all explanatory factors into account. Among the five components of MetS, subjects with hypertriglyceride (aOR=1.43, 95% CI: 1.17-1.75) and hyperglycemia (aOR=1.30, 95% CI: 1.02-1.67) had higher risk of presenting OPM compared with those within normal ranges. The association between MetS and OPM still persisted even in non-chewers (aOR=1.85, 95% CI: 1.42-2.40) while other risk factors were controlled. We demonstrate a positive association between MetS and OPM, which is independent of areca nut chewing and other confounding factors. This finding provides an insight into a new direction of preventing OPM in contrast to conventional viewpoint focusing on the most important factor of area nut chewing.     

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.     

Areca nut chewing and esophageal squamous-cell carcinoma risk in Asians: A meta-analysis of case–control studies

Purpose

This meta-anlaysis quantitatively assessed an overall independent association between areca nut chewing and esophageal squamous-cell carcinoma in Asians.

Methods

Studies (case–control and/or cohort) were identified by searching the PubMed, Medline, and Embase databases through 30 September, 2012, using the keywords o/esophageal squamous-cell carcinoma, o/esophageal cancer, chewing areca nut, betel quid without tobacco, Asia, and the reference lists of retrieved articles. Random-effects model was used to compute adjusted summary OR_RE for the main effect of areca nut chewing and additive (biological) interaction between areca nut chewing and tobacco smoking along with their corresponding 95 % confidence intervals (CI). To quantify the impact of between-study heterogeneity on adjusted main-effect summary OR_RE, Higgins’ H and I ² statistics along with their 95 % uncertainty intervals were used. Funnel plot and Egger’s test were used to evaluate publication bias.

Results

Meta-analysis of 12 case–control studies (2,836 cases; 9,553 controls) showed that areca nut chewing was significantly and independently associated with an increased risk of esophageal squamous-cell carcinoma (adjusted main-effect summary OR_RE = 3.05; 95 % CI 2.41, 3.87). Furthermore, pooled analysis of additive interaction between areca nut chewing and tobacco smoking reported by six of the included studies revealed manifold increased risk of esophageal squamous-cell carcinoma among those who indulged in both the practices compared with those who practiced none (adjusted additive interaction-effect summary OR_RE = 6.79; 95 % CI 4.71, 9.79). There was no significant publication bias (p = 0.289).

Conclusions

Areca nut chewing was significantly and independently associated with an increased risk of esophageal squamous-cell carcinoma in Asians. Additionally, individuals who indulged in both areca nut chewing and tobacco smoking had manifold increased risk of esophageal squamous-cell carcinoma. The efforts aimed at curtailing the addiction to areca nut chewing may contribute to lower the incidence of esophageal squamous-cell carcinoma and related mortality in Asians.     

Betel quid without tobacco as a risk factor for oral precancers

The IARC monographs recently classified chewing betel quid without tobacco as a human carcinogen. Several studies in Taiwan have reported that betel quid without tobacco may increase the risk of oral precancers such as oral leukoplakia and oral submucous fibrosis. However in India, since most betel quid chewers prefer to add tobacco to the quid, the independent effect of betel quid on the risk of oral precancers is difficult to assess and has not yet been fully explored. We conducted a large case-control study in Kerala, India, including 927 oral leukoplakia cases, 170 oral submucous fibrosis cases, 100 erythroplakia cases, 115 multiple oral precancer cases and 47,773 controls. The focus of this reanalysis is on the minority of individuals who chewed betel quid without tobacco. Among nonsmokers and nondrinkers, chewing betel quid without tobacco conferred ORs of 22.2 (95%CI = 11.3, 43.7) for oral leukoplakia, 56.2 (95%CI = 21.8, 144.8) for oral submucous fibrosis, 29.0 (95%CI = 5.63, 149.5) for erythroplakia and 28.3 (95%CI = 6.88, 116.7) for multiple oral precancers, after adjustment for age, sex, education and BMI. Dose-response relationships were observed for both the frequency and duration of betel quid chewing without tobacco on the risk of oral precancers. In conclusion, our study supports the hypothesis that chewing betel quid without tobacco elevates the risks of various oral precancers.     

Betel quid chewing as a risk factor for hepatocellular carcinoma: a case-control study

The role of betel quid chewing in the aetiology of hepatocellular carcinoma (HCC) was evaluated in a case-control study including 263 pairs of age- and sex-matched HCC patients and healthy controls. Serum hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus (anti-HCV) were determined, and standardized personal interview conducted using a structured questionnaire. Multivariate analysis indicated that betel quid chewing (odds ratio (OR), 3.49; 95% confidence interval (CI), 1.74-6.96), HBsAg (OR, 16.69; 95% CI, 9.92-28.07), anti-HCV (OR, 38.57; 95% CI, 18.15-81.96), and educational duration of less than 10 years (OR, 1.71; 95% CI, 1.05-2.78) are independent risk factors of HCC. In addition, there was an additive interaction between betel quid chewing and chronic infection with either hepatitis B virus (synergy index, 5.37) or hepatitis C virus (synergy index, 1.66). Moreover, risk on HCC increased as duration of betel quid chewing increased, or amount of betel quid consumed (each P for trend < 0.0001).     

The Risk of Oral Cancer among Different Categories of Exposure to Tobacco Smoking in Sri Lanka

Background: The global incidence of oral squamous cell carcinoma (OSCC) is on the rise with no improvement seen in survival rates. Tobacco consumption varies depending on geographic location, ethnicity and culture. The present case-controlled study aimed to determine the relative risk of OSCC for different tobacco consumption patterns in a selected Sri Lankan population. Methods: One hundred and five patients with histopathologically confirmed OSCC attending the National Cancer Institute (Apeksha Hospital) of Sri Lanka and 210 age and gender-matched controls from the community responded to an interviewer-administered questionnaire regarding their smoking and betel-quid chewing (with/ without smokeless tobacco) habits were included in the study. The odds ratios (OR) and 95% confidence intervals (CI) were calculated. p<0.05 was considered as statistically significant. Results: The overall risk of OSCC increased 2.93-fold for smokers. Those smoking two packets of cigarettes or more per day (OR=5.56; 95% CI-2.822-10.984; p=0.000) had more than double the risk of OSCC than those smoking 1-2 packets per day. Smoking for more than 20 years had a 3.4-fold risk of OSCC. Consumption of betel quid containing tobacco (smokeless tobacco) had a 4.26-fold higher risk for OSCC (OR=4.26; 95% CI-2.21-8.21; p=0.000), and the risk increased when all four ingredients (betel leaf, slaked lime, areca nut, and tobacco) were consumed together (OR=4.26; 95% CI-2.34-7.74; p=0.000). The combined effect from concurrent smoking and betel chewing emerged as the highest risk for OSCC (OR=15.34) which significantly exceeded the risks evident for the two habits practised in isolation from each other. Conclusions: Use of smokeless tobacco, consumption of all four ingredients together, duration of smoking, the number of cigarettes smoked per day and combined consumption of betel quid and smoking are significant risk factors in the development of OSCC among Sri Lankans.     

Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujarat, India.

In Gujarat, India, 6718 industrial workers, over 35 years of age, with oral leukoplakia (confirmed clinically and microscopically), were studied. After 2 years, 4762 (71%) of the individuals were re-examined. The buccal mucosa was the most common site of occurrence; 98.3% of these individuals had oral habits, with smoking alone or smoking in combination with "pan" or "supari" chewing accounting for 74.9% of the habit forms. Six individuals (0.13%) with oral leukoplakia developed oral carcinomas within 2 years. This incidence of malignant transformation was equivalent to 63/100,000 per year, which far exceeds that of new oral cancers expected even in high-risk populations. While 57.3% the leukoplakic lesions remained unchanged during a 2-year interval, 31.6% disappeared and 11% had an altered appearance. This study confirmed the precancerous nature of oral leukoplakia.     

Role of tobacco smoking, chewing and alcohol drinking in the risk of oral cancer in Trivandrum, India: a nested case-control design using incident cancer cases

Oral cancer is one of the most common cancers in the world, with two-thirds of the cases occurring in developing countries. While cohort and nested case-control study designs offer various methodological strengths, the role of tobacco and alcohol consumption in the etiology of oral cancer has been assessed mainly in case-control studies. The role of tobacco chewing, smoking and alcohol drinking patterns on the risk of cancer of the oral cavity was evaluated using a nested case-control design on data from a randomized control trial conducted between 1996 and 2004 in Trivandrum, India. Data from 282 incident oral cancer cases and 1410 matched controls were analyzed using multivariate conditional logistic regression models. Tobacco chewing was the strongest risk factor associated with oral cancer. The adjusted odds ratios (ORs) for chewers were 3.1 (95% confidence interval (CI) = 2.1–4.6) for men and 11.0 (95%CI = 5.8–20.7) for women. Effects of chewing pan with or without tobacco on oral cancer risk were elevated for both sexes. Bidi smoking increased the risk of oral cancer in men (OR = 1.9, 95%CI = 1.1–3.2). Dose-response relations were observed for the frequency and duration of chewing and alcohol drinking, as well as in duration of bidi smoking. Given the relatively poor survival rates of oral cancer patients, cessation of tobacco and moderation of alcohol use remain the key elements in oral cancer prevention and control.     

Betel nut and tobacco chewing; potential risk factors of cancer of oesophagus in Assam, India

Cancer of the oesophagus is the most commonly diagnosed cancer in males in Assam, in north-eastern India, and ranks second for females. The chewing of betel nut, with or without tobacco and prepared in various ways, is a common practice in the region and a case-control study has been designed to study the pattern of risk associated with different ways of preparing and chewing the nuts. 358 newly diagnosed male patients and 144 female have been interviewed together with 2 control subjects for each case chosen at random from among the attendants who accompanied patients to hospital. There were significant trends in risk ratios associated with the frequency of chewing each day, with the duration of chewing in years and with the age at which the habit was started that were apparent for both males and females and which remained significant after allowance was made for other known risk factors, notably tobacco smoking and alcohol consumption. The adjusted ratios, in comparison with non-chewers, were 13.3 M and 5.7 F for chewing more than 20 times a day, 10.6 M and 7.2 F for persons who had chewed for more than 20 years and 10.3 M and 5.3 F for those who had started before the age of 20. Among the different combinations of ingredients that were chewed the adjusted odds ratios were highest for those who had been using fermented betel nut with any form of tobacco (7.1 M and 3.6 F). The risk associated with tobacco smoking and alcohol consumption, which are high in some parts of the world, were less in Assam than those associated with the chewing of betel nut.     

Glutathione S-transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokers

Polymorphism in glutathione S-transferase (GST) genes, causing variations in enzyme activities, may influence susceptibility to oral cancer and leukoplakia in smokers and/or smokeless tobacco users. In this case-control study consisting of 109 leukoplakia and 256 oral cancer patients and 259 controls, genotype frequencies at GSTM1, GSTT1, GSTM3 and GSTP1 loci were determined by polymerase chain reaction-restriction fragment length polymorphism methods and analyzed by multiple logistic regression to determine the risks of the diseases. There were no significant differences in the distributions of GSTM1, GSTM3 and GSTT1 genotypes in patients and controls when all individuals were compared. In contrast, frequencies of ile/ile genotype at codon 105 and variant val-ala haplotype of GSTP1 was significantly higher (OR = 1.5; 95% CI = 1.0-2.0) and lower (OR = 1.4; 95% CI = 1.0-1.9) in oral cancer patients compare to controls, respectively. The impacts of all genotypes on risks of oral cancer and leukoplakia were also analyzed in patients with different tobacco habits and doses. Increased risks of cancer and leukoplakia were observed in tobacco smokers with GSTM3 (A/A) genotype (OR = 2.0, 95% CI = 1.0-4.0; OR = 2.0, 95% CI = 1.0-4.4, respectively). So, GSTM3 (A/A) genotype could become one of the markers to know which of the leukoplakia would be transformed into cancer. Heavy tobacco chewing (> 124 chewing-year) increased the risk of cancer in individuals with GSTT1 homozygous null genotype (OR = 3.0; 95% CI = 1.0-9.8). Furthermore, increased lifetime exposure to tobacco smoking (> 11.5 pack-year) increased the risk of leukoplakia in individuals with GSTM1 homozygous null genotype (OR = 2.4; 95% CI = 1.0-5.7). It may be suggested that polymorphisms in GSTP1, GSTM1, GSTM3 and GSTT1 genes regulate risk of cancer and leukoplakia differentially among different tobacco habituals.     

Impact of RECK gene polymorphisms and environmental factors on oral cancer susceptibility and clinicopathologic characteristics in Taiwan

Oral cancer is the fourth common male cancer and causally associated with environmental carcinogens in Taiwan. The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) has a significant effect on tumorigenesis by limiting angiogenesis and invasion of tumors through the extracellular matrix. RECK downregulation has been confirmed in many human cancers and associated with lymph node metastasis clinically. In the present hospital-based case-controlled study, the demographic, RECK genotype and clinicopathologic data from 341 male oral cancer patients and 415 cancer-free controls were investigated. We found that RECK rs10814325, rs16932912, rs11788747 or rs10972727 polymorphisms were not associated with oral cancer susceptibility. Among 488 smokers, RECK polymorphisms carriers with betel quid chewing have a 7.62-fold [95% confidence interval (CI), 2.96-19.64] to 25.33-fold (95% CI, 9.57-67.02) risk to have oral cancer compared with RECK wild-type carrier without betel quid chewing. Among 352 betel quid chewers, RECK polymorphisms carriers with smoking have a 6.68-fold (95% CI, 1.21-36.93) to 18.57-fold (95% CI, 3.80-90.80) risk to have oral cancer compared with those who carried wild-type without smoking. In 263 betel quid chewing oral cancer patients, RECK rs10814325 polymorphism have a 2.26-fold (95% CI, 1.19-4.29) risk to have neck lymph node metastasis compared with RECK wild-type carrier. These results support that gene-environment interactions between the RECK polymorphisms, smoking and betel quid may alter oral cancer susceptibility and metastasis.     

Assessment of risk factors for oral squamous cell carcinoma in Chidambaram, Southern India: a case-control study.

Oral squamous cell carcinoma, the fifth most common cancer worldwide, is a major cause of morbidity and mortality in India. The effect of lifestyle factors, including tobacco chewing, smoking and alcohol drinking, diet and dental care, on the risk of oral cancer was investigated in a case-control study conducted in Rajah Muthiah Dental College and Hospital, Annamalainagar, Annamalai University, Chidambaram, Tamil Nadu, India during the period 1991-2003. The study included 388 oral squamous cell carcinoma cases and an equal number (388) of age and sex-matched controls. All participants were interviewed using a structured questionnaire that contained data on demographic factors, family history of cancer, tobacco habits, use of alcohol, frequency, duration, cessation of these habits, dietary practices and oral hygiene. The data were analysed using multiple logistic regression model. Among people with chewing habits, those who chewed betel quid with tobacco [odds ratio (OR) 3.19, 95% confidence interval (CI): 0.48-2.13] and tobacco alone (OR 2.89) showed a greater risk than controls. Bidi smoking (OR 4.63) and alcohol drinking (OR 1.65) emerged as significant risk factors for oral cancer. These three habits showed increasing risk with increasing frequency and increase in duration of habits. Addition of alcohol to other habits also enhanced the risk for oral cancer. The combination of chewing and smoking together with alcohol drinking showed very high relative risk (OR 11.34). A positive association was observed between non-vegetarian diet, poor oral hygiene and poor dentition with the risk of oral squamous cell carcinoma. The fact that these risk factors are modifiable emphasizes the need for increasing awareness among the general public and policy makers as a first step in the prevention and control of oral squamous cell carcinoma.