R. B. Bhonsle

An epidemiologic assessment of cancer risk in oral precancerous lesions in India with special reference to nodular leukoplakia.

A cohort of 12,212 tobacco users was followed up annually to assess malignant potential of oral precancerous lesions in the Ernakulam district in Kerala, India. A total of 19 new oral cancers were diagnosed over a period of 8 years, and 15 (79%) of these arose from some preexisting precancerous lesion or condition. Nodular leukoplakia showed highest rate of malignant transformation (16% per year) as six of 13 nodular leukoplakia underwent malignant transformation over a mean follow‐up period of 2.8 years. The relative risk (3243.2) compared with individuals with tobacco habits but without any precancerous oral lesion was also the highest for nodular leukoplakia. In addition, nodular leukoplakia was associated with submucous fibrosis in two patients, which progressed to oral cancer and was the clinical diagnosis for four lesions that turned out to be malignant on histopathologic examination. Nodular appearance was noted in two other precursor lesions as well. Thus, 14 of 19 oral cancers (74%) were either preceded by nodular leukoplakia and with lesions showing a distinct nodular appearance, or had the clinical appearance of nodular leukoplakia.

Epidemiology of Cancer by Tobacco Products and the Significance of TSNA

Globally, oral cancer is one of the ten common cancers. In some parts of the world, including the Indian subcontinent, oral cancer is a major cancer problem. Tobacco use is the most important risk factor for oral cancer. The most common form of tobacco use, cigarette smoking, demonstrates a very high relative risk--in a recent cohort study (CPS II), even higher than lung cancer. In areas where tobacco is used in a smokeless form, oral cancer incidence is generally high. In the West, especially in the U.S. and Scandinavia, smokeless tobacco use consists of oral use of snuff. In Central, South, and Southeast Asia smokeless tobacco use encompasses nass, naswar, khaini, mawa, mishri, gudakhu, and betel quid. In India tobacco is smoked in many ways; the most common is bidi, others being chutta, including reverse smoking, hooka, and clay pipe. A voluminous body of research data implicating most of these forms of tobacco use emanates from the Indian subcontinent. These studies encompass case and case-series reports, and case-control, cohort, and intervention studies. Collectively, the evidence fulfills the epidemiological criteria of causality: strength, consistency, temporality, and coherence. The biological plausibility is provided by the identification of several carcinogens in tobacco, the most abundant and strongest being tobacco-specific N-nitrosamines such as N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These are formed by N-nitrosation of nicotine, the major alkaloid responsible for addiction to tobacco. The etiological relationship between tobacco use and oral cancer has provided us with a comprehensive model for understanding carcinogenesis.

INTERVENTION STUDY FOR PRIMARY PREVENTION OF ORAL CANCER AMONG 36 000 INDIAN TOBACCO USERS

In a house-to-house survey, 36 471 tobacco chewers and smokers were selected from the rural population in three areas of India. These individuals were interviewed for their tobacco habits and examined for the presence of oral leukoplakia and other precancerous lesions, first in a baseline survey, and then annually over a 5-year period. By personal advice and via the mass media they were encouraged to give up their tobacco habits. The follow-up rate was 97%. The control cohort was provided by the first 5-year results from a 10-year follow-up study conducted earlier in the same areas with the same methodology but on different individuals without any educational intervention. In Ernakulam district (Kerala) and Srikakulam district (Andhra) substantially more people stopped their tobacco habit and reduced the frequency of tobacco use in the intervention cohort than in the control cohort; in Bhavnagar district (Gujarat) the intervention group showed only a slightly higher proportion stopping their tobacco habits and no difference in the proportion reducing them. The 5-year age-adjusted incidence rate of leukoplakia in Ernakulam district was 11.4 in the intervention group versus 47.8 among men, and 5.8 versus 33.0 among women; and for palatal lesions in Srikakulam district the corresponding figures were 59.8 versus 260.8 among men and 289.5 versus 489.5 among women. In Bhavnagar the incidence rate of leukoplakia did not differ between the cohorts. Since most oral cancers are preceded by precancerous lesions, education on tobacco habits should be a feasible and effective approach to primary prevention of oral cancer.

Development and testing of a quantitative food frequency questionnaire for use in Kerala, India

OBJECTIVE To develop and test a food frequency questionnaire (FFQ) for use in rural areas of Kerala, India. DESIGN Based on food use and market surveys of the study area, a quantitative 81-item interviewer-administered FFQ was developed. A validation study was conducted consisting of 24-h diet recalls (24HR) administered on 8 days randomly selected over an entire year and two administrations of the FFQ, one at the beginning of the 1-year period and the other at the end. FFQ and 24HR-derived nutrient scores were compared using correlation and regression analyses and by examining differences in the nutrient scores. SETTING Rural villages in Ernakulum district, Kerala, South India. SUBJECTS In each of 30 households, the male head of household and female food preparer were enrolled. RESULTS Pearson (parametric) correlation coefficients (r(p)) averaged about 0.50 in comparing nutrient scores derived from the 24HR with those from the first FFQ and about 0.55 in comparing the second FFQ. On average, Spearman correlation coefficients (r(s)) were slightly lower than the r(p) in comparing the scores derived from the first FFQ, but virtually identical for the second FFQ. Regression analyses indicated better agreement in the comparison of the 24HR-derived scores with the first FFQ than the second FFQ. Difference scores, however, tended to be larger in comparing the first FFQ scores with the 24HR. CONCLUSIONS This FFQ produces results broadly comparable to those used in Europe and North America, indicating its suitability for comparing exposures within a study population in reference to health-related endpoints.

Incidence and early forms of oral submucous fibrosis

The yearly incidence of submucous fibrosis per 100,000 person-years was found to be 9 for males and 20 for females over a 10-year period in the Ernakulam district of Kerala, South India. In the same area possible early case of submucous fibrosis, under the clinical diagnosis of leukoplakia and lichen planus, showed the typical histologic features of the disease.

Influence of Dietary Factors on Oral Precancerous Lesions in a Population-Based Case-Control Study in Kerala, India

Although tobacco is the primary etiologic factor for oral precancerous lesions in India, evidence from other sources indicates that diet may modify risk. This case–control study was designed to minimize a variety of biases in its attempt to investigate the relation between diet and oral precancerous lesions.

Dietary exposures and oral precancerous lesions in Srikakulam District, Andhra Pradesh, India

OBJECTIVE To test the effect of dietary nutrients on oral precancerous lesions in a reverse-smoking (i.e. smoking with the glowing end inside the mouth) population in South India. DESIGN Case-control. Cases with precancerous lesions were matched to an equal number of lesion-free controls matched on age (+/- 5 years), sex and village. All subjects used tobacco in some form. Dietary data were obtained using an interviewer-administered food-frequency questionnaire, designed for use in this population. All interviews were conducted blinded to the disease status of the subject. Data were analysed using logistic regression. SETTING Nineteen rural villages in Srikakulam District, Andhra Pradesh. SUBJECTS From a survey of 6007 tobacco users, 485 (79% women) were found to have precancerous, mostly palatal, lesions (cases), and 487 lesion-free subjects were selected as controls. RESULTS All eligible subjects consented to participate and nearly all (> 99%) had complete data for analyses. Reverse smoking was the most common form of tobacco use among cases (81.9%) and controls (73.5%), and reverse smokers were 5.19 times more likely than chewers to have these lesions (95% confidence interval = 1.35, 19.9). After controlling for relevant covariates, including the type of tobacco use, protective linear effects were observed for zinc (70% reduction across the interquartile range, P < 0.002), calcium (34% reduction, P < 0.002), fibre (30% reduction, P < 0.009), riboflavin (22% reduction, P < 0.03) and iron (17% reduction, P < 0.05). CONCLUSIONS Several dietary nutrients appear to protect against oral precancerous lesions that are strongly associated with reverse smoking. The results of this study indicate scope for targeting dietary factors in preventing oral cancer, which should be coupled with aggressive anti-tobacco use efforts.

Determinants of accuracy in estimating the weight and volume of commonly used foods: A cross‐cultural comparison

Inaccuracy of dietary self‐reports may result from an inability to estimate portion sizes of foods. To determine the influence of cultural factors, 162 subjects at three study locations in rural India and 100 subjects in Massachusetts, USA were asked to estimate weights and volumes of four commonly used food items. Compared with their Massachusetts counterparts, subjects in India evinced errors in their estimates of food weights which averaged only about 20% as large, with standard deviations less than half as large. In the combined data from the four study locations, relative to those with just primary education, individuals with some college overestimated the small and large reference weights by 79% and 52%, respectively (p <0.01). Implications of this research, including the use of quantitative dietary assessment methods in low literacy populations with relatively little formal education and possibilities of bias in epidemiologic studies, are discussed.

Oro-facial lesions of tuberous sclerosis

The occurrence of tuberous sclerosis among Indians has not been reported earlier. In the Ernakulam District, Kerala, in a kindred of 27, seven cases with oro-facial or facial lesions of tuberous sclerosis were observed. None of the individuals was mentally retarded, nor was there any history of systemic anomalies. The cases in this series possibly represent an incomplete form (Forme frustes) of the syndrome. The pedigree in the present material supports the autosomal dominant inheritance.