This study found that betel quid chewing was the principal cause of OL and OSF. Subjects who ever chewed areca nut experienced a more than 11-fold risk of these precancerous conditions. The risks increased with the duration and frequency of the habit, as previously shown in Pakistan, India, Taiwan and Mainland China (Mehta et al, 1981
; Maher et al, 1994
; Tang et al, 1997
; Shiu et al, 2000
The chewing of betel quid is practised in several different ways in various countries, while the major components are comparatively consistent. In India and Southeast Asia, tobacco was usually used as an ingredient for areca nut products (called ‘pan’), but not in Taiwan. A higher relative risk of oral cancer for betel quid chewing with tobacco was notably higher than that for betel quid chewing without tobacco, and the evidence for OL was also in the same direction (Gupta et al, 1982
). Our study showed that non-smokers and nondrinkers who chewed betel quid had, respectively, a 10.0–15.6- and 26.5–39.3-fold significant risk of OL and OSF (), and both risks were lower than that reported for tobacco-contained areca nut products (OR=17.4 and 44.1 for OL and OSF, respectively) (IARC, 1985
; Hashibe et al, 2000
). The difference in risks between areca nut with and without tobacco implies that tobacco could have an additional effect on OL and OSF.
Significantly elevated risks of OL and OSF were registered at the lowest levels of betel chewing quantity (1–10 pieces
) and duration (1–10 years). The data indicated that even a relatively short exposure is sufficient to induce leukoplakia or mucous fibrosis, as previously suggested (Seedat and Van Wyk, 1988
; Maher et al, 1994
). Arecoline, the most abundant alkaloid in areca nut, has been observed experimentally to stimulate collagen synthesis by fibroblasts in vitro
(Canniff and Harvey, 1981
). Studies of human buccal fibroblasts found that arecoline was not only cytotoxic but stimulated double-stranded polynucleic acid synthesis; both might act synergistically on the pathogenesis of OSF as well as oral cancer (Chang et al, 1998
OL and OSF are clinically distinct precancerous lesions that precede the development of oral cancer. Our study showed that the risk of OSF at each exposure level of betel quid chewing was stronger than those of OL, although the difference was not large enough to reject the null. Similar results were found in large-scale case–control studies conducted in India (Hashibe et al, 2000
). We also found that mainly younger patients had OSF compared with mainly older patients with OL. The fact that OSF patients started betel quid chewing at a younger age than OL patients and chewed more quids per day may partly explain the age differences between the two diseases.
Our multivariate analyses indicated that cigarette smoking was an independent risk factor for OL, but not for OSF. While the associations between tobacco smoking and the two types of oral premalignant diseases have not been definitely established, comparable findings were observed in India and Europe (Banoczy et al, 2001
; Hashibe et al, 2000
). We found a significant precancer risk of cigarette smoking among OL patients who did not chew betel. In contrast, the effects of betel quid chewing alone on OSF among nonsmokers and nondrinkers were much higher than those on OL (OR ratios
1.7), reflecting the substantial role of smoking in OL, although the effect of betel quid chewing is much stronger on OSF, as discussed earlier. In addition, it has been noticed that the risk of OL and OSF is greatly increased in the presence of both betel quid chewing and smoking (). Cigarette smoking was found to modify the effect of betel quid chewing in OL based on an additive interaction model. However, the joint risk of OSF for the two factors was still higher than the combined risk of OL, assessed by multiple logistic regression models.
Although ethanol has been recognized as a solvent that may damage the oral cells and increase the mucosal penetration of certain oral carcinogens (Hashibe et al, 2000
), the role of alcohol drinking in the development of OL is still unclear. In a cross-sectional study, an independent effect of alcohol use on OL was not identified (Gupta, 1984
) nor in Uzbekistan (Evstifeeva and Zaridze, 1992
). In contrast, studies in Kenya (Macigo et al, 1996
) and India (Hashibe et al, 2000
) suggested that drinking was a moderate risk factor, and a clear dose–response relation between alcohol consumption and OL was evidenced. In our study, alcohol intake was not associated with OL. Among OL patients with precancerous lesion, 88.7 and 98.1% of alcohol users were also betel quid and tobacco consumers, respectively. The nonsignificant risks in the multiple regression models indicated that the effect of drinking was explained by betel quid chewing and cigarette smoking. Alcohol use was not an important risk factor for OL in our southern Taiwan population. On the other hand, our study indicated that alcohol consumption was not related to OSF. This result was consistent with the findings from previous studies (Maher et al, 1994
; Yang et al, 2001
Oral cancer has been one of the 10 leading causes of cancer deaths in Taiwan since 1982. The mortality of oral cancer increased about 2.6-fold from 1971 to 1997 (Department of Health (ROC), 1998
), making its prevention an important public health issue in Taiwan. Since it is often preceded by OL and OSF, and the cessation of areca nut chewing has been associated with a regression in the incidence of OL (Gupta et al, 1995
), study of their risk factors and their population attributable risk proportion may allow better directed prevention efforts. Our study showed that 73.2 and 56.4% of the aetiologic fraction of OL were, respectively, attributable to betel quid chewing and cigarette smoking. In contrast, the habit of chewing betel quid accounted for 85.4% of attributable risk of OSF. Additionally, it is reasonable to expect that the avoidance of chewing and smoking may possibly prevent 86.5% of the two oral premalignant diseases, and thereby be of considerable health benefit to Taiwan.
One concern in this study is that the oral cavity status of controls was not examined. Since the incidence of the two oral diseases was relatively low, the bias resulting from the inclusion of possible cases in the control group should be limited, and should, if anything, tend to underestimate the risks.
In summary, the chewing of betel quid significantly contributed to the risks of having OL and OSF, and an overwhelming majority were attributable to the practise of areca nut chewing. Cigarette smoking also had a substantial role in the occurrence of OL and potentiated the effect of betel quid chewing.