Nonlinear association between betel quid chewing and oral cancer: Implications for prevention

Sreenath Arekunnath Madathil, Marie Claude Rousseau, Willy Wynant, Nicolas F. Schlecht, Gopalakrishnan Netuveli, Eduardo L. Franco, Belinda Nicolau

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Purpose Betel quid chewing is a major oral cancer risk factor and the human papillomaviruses (HPV) may play an aetiological role in these cancers. However, little is known about the shape of the dose-response relationship between the betel quid chewing habit and oral cancer risk in populations without HPV. We estimate the shape of this dose-response relationship, and discuss implications for prevention. Methods Cases with oral squamous cell carcinoma (350) and non-cancer controls (371) were recruited from two major teaching hospitals in South India. Information on socio-demographic and behavioral factors was collected using a questionnaire and the life grid technique. The effect of daily amount of use and duration of the habit were estimated jointly as risk associated with cumulative exposure (chew-years). The shape of the dose-response curve was estimated using restricted cubic spline transformation of chew-years in a conditional logistic regression model. Risk estimates for low dose combinations of daily amount and duration of the habit were computed from flexible regression. Results Most (72%) oral cancer cases were betel quid chewers in contrast to only 18% of controls. A nonlinear dose-response relationship was observed; the risk increased steeply at low doses and plateaued at high exposures to betel quid (>425 chew-years). A threefold increase in risk (OR = 3.92, 95%CI: 1.87–8.21) was observed for the lowest dose; equivalent to the use of one quid per day for one year. Conclusion Our findings may be used to counsel people to refrain from even low betel quid chewing.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalOral Oncology
StatePublished - Sep 1 2016


  • Betel quid chewing
  • Dose-response
  • Nonlinearity
  • Oral cancer
  • Restricted cubic spline

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research


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