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

Oral Oncol. 2016 Sep;60:25-31. doi: 10.1016/j.oraloncology.2016.06.011. Epub 2016 Jul 5.


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.

Keywords: Betel quid chewing; Dose-response; Nonlinearity; Oral cancer; Restricted cubic spline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Areca*
  • Carcinoma, Squamous Cell / epidemiology*
  • Case-Control Studies
  • Female
  • Humans
  • India
  • Male
  • Mastication
  • Middle Aged
  • Mouth Neoplasms / epidemiology*
  • Nonlinear Dynamics
  • Risk Factors