Oral Diseases (1998) 4, 200–206  1998 Stockton Press All rights reserved. 1354-523X/98 $12.00 http://www.stockton-press.co.uk/od Dietary factors in oral leukoplakia and submucous fibrosis in a population-based case control study in Gujarat, India PC Gupta 1 , JR Hebert 2 , RB Bhonsle 1 , PN Sinor 1 , H Mehta 1 , FS Mehta 1 1 Epidemiology Research Unit, Tata Institute of Fundamental Research, Homi Bhabha Road, Bombay 400005, India; 2 Division of Preventive and Behavioral Medicine, Department of Medicine, University of Massachusetts Medical School, 55, Lake Avenue, Worcester, MA 01655, USA OBJECTIVES: To investigate the relationship of specific nutrients and food items with oral precancerous lesions among tobacco users. DESIGN : A population-based case-control study. SET T IN G: Villages in Palitana taluk of Bhavnagar district, Gujarat, India. SUBJECTS AND METHODS: An interviewer-adminis- tered food frequency questionnaire, developed and vali- dated for this population, was used to estimate nutrient intake in blinded, house-to-house interviews. Among 5018 male tobacco users, 318 were diagnosed as cases. An equal number of controls matched on age ( 5 years), sex, village, and use of tobacco were selected. MAIN OUTCOME MEASURES: Odds ratios (OR) from multiple logistic regression analysis controlling for rel- evant variables (type of tobacco use and economic status). RESULTS: A protective effect of fibre was observed for both oral submucous fibrosis (OSF) and leukoplakia, with 10% reduction in risk per g day 1 ( P  0.05). Ascorbic acid appeared to be protective against leukoplakia with the halving of risk in the two highest quartiles of intake ( versus the lowest quartile: OR = 0.46 and 0.44, respect- ively; P  0.10). A protective effect of tomato consump- tion was observed in leukoplakia and a suggestion of a protective effect of wheat in OSF. CO N CLU SIO N : In addition to tobacco use, intake of spe- cific nutrients may have a role in the development of oral precancerous lesions. Keywords: India; oral neoplasms; precancerous conditions; nutrition; diet; -carotene; zinc; iron; ascorbic acid; submucous fibrosis; leukoplakia; tobacco chewing; smoking Introduction Oral cancer is the sixth commonest cancer in the world (Parkin et al, 1993). Its incidence is particularly high in India, some other countries in Asia, and certain places in Correspondence: Dr Prakash C Gupta, Epidemiology Research Unit, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai- 400 005, India Received 16 February 1998; revised and accepted 20 April 1998 the Western hemisphere, e.g., parts of France and Brazil. In the Western hemisphere, smoking and alcohol drinking are major risk factors, whereas in India, the chewing of tobacco products, in addition to smoking in various forms, is primarily responsible for the high incidence. The WHO have estimated that 90% of oral cancers in India among men are attributable to the chewing and smoking of tobacco (WHO, 1984). Nutritional risk factors have also been implicated in can- cers of the oral cavity. A number of studies have indicated that the consumption of various vegetables and fruits reduces risk. These relationships may be independent of other risk factors and show a dose-response (Marshall et al, 1982; Winn et al, 1984; Franco et al, 1989). However, there is considerable potential for confounding, and this may be difficult or impossible to control in most epidemiol- ogic studies on the subject (Marshall and Boyle, 1996). Oral cancer is often preceded by oral precancerous lesions and conditions (Pindborg, 1980). Conversely, the relative risk of individuals with oral precancerous lesions developing oral cancer has been demonstrated to be very high, even after controlling for the use of tobacco (Gupta et al, 1989). The association of oral precancerous lesions with tobacco habits follows a pattern similar to that of oral cancer (Gupta et al, 1980). Because the prevalence of oral precancerous lesions is much higher than that of oral can- cer, these lesions provide useful clinical markers for oral cancer. They have been used as such in large-scale inter- vention trials (Gupta et al, 1992a). A focus on precancerous lesions avoids much of the potential for measurement bias and confounding that affect most studies of diet and oral cancer (Marshall and Boyle, 1996) because many of these conditions, such as oral leuko- plakia, would have no plausible effect on dietary intake. It should be noted, however, that oral submucous fibrosis (OSF) may affect intake to some extent because of associa- ted symptoms, a common one being a burning sensation on intake of spicy food. An additional rationale for conducting a study in an Indian population included a probable wide range of variability in nutrient exposures (Rao, 1987; NIN, 1991). The primary goal of this research was to test the relation- ship between precancerous changes in the mouth and diet- ary intake of specific nutrients; in particular the antioxidant vitamins, several minerals, the B-vitamins, and fibre