Abstract

Abstract Background Northeast India has a high incidence of esophageal cancer(EC), with age-adjusted incidences ranging from 19 to 50 per 100,000 (in females and males respectively). This is over ten times the average incidence of EC in India. The local preparation of raw betel nut,‘kwai’, is integral to the culture, but its role has not been established. This study aimed to assess the role of betel nut, with or without tobacco as a causative agent for EC. The role of alcohol was also studied. Methods A multi-centric, matched case-control study was performed from October 2022 to March 2024 in three centres situated in the Northeast region of India. All cases of biopsy proven squamous EC, arising from the cricopharynx to the gastroesophageal junction were included, with matched controls (1:3 ratio) being patients visiting the hospital for minor ailments and healthy volunteers from the community. A validated questionnaire was administered by trained trial coordinators. The data was analysed using a conditional multivariate logistic regression which incorporated the individual matching of cases with 3 controls. A p-value of < 0.05 was considered statistically significant. Results A total of 185 cases and 556 controls were matched for age (± 5 years), ethnicity, and gender. There was an increased risk of EC for those consuming betelnut with slaked lime [Calcium hydroxide Ca(OH)2] (Odds Ratio(OR) of 3.77 (Confidence Interval(CI) 1.30-10.92)); alcohol (OR 2.00 CI: 1.80-6.67) and tobacco (OR 3.47 CI:1.80-6.67). The risk was higher for those who swallowed the betel quid and juice as compared with those who spit it out (OR 4.01 CI: 2.24-6.73). The risk was increased in those consuming betelnut while hungry, instead of a meal (OR 10.40 CI 3.66-29.57). The risk was increased in those with no formal education (OR of 4.13 CI: 2.01-8.49). On adjusting with other risk factors (tobacco and alcohol), the risk was highest for betelnut with tobacco (OR 7.84 CI 2.12-29.90) and betelnut with alcohol (OR 2.84 CI 1.11-7.29). All these OR were statistically significant. Conclusion Consumption of betelnut with slaked lime increases the risk of EC. This risk is increased by the concomitant use of tobacco and alcohol.

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