title: Nonlinear association between betel quid chewing and oral cancer: Implications for prevention.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our findings may be used to counsel people to refrain from even low betel quid chewing.
authors.affiliation: Faculty of Dentistry, 2001 McGill College Ave, Suite 500, McGill University, Montreal, QC H3A 1G1, Canada; Epidemiology and Biostatistics Unit, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, QC H7V 1B7, Canada.
authors.forename: Sreenath Arekunnath
authors.initials: SA
authors.lastname: Madathil
authors.affiliation: Faculty of Dentistry, 2001 McGill College Ave, Suite 500, McGill University, Montreal, QC H3A 1G1, Canada; Epidemiology and Biostatistics Unit, INRS-Institut Armand-Frappier, 531 boulevard des Prairies, Laval, QC H7V 1B7, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Rousseau
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, 1020 Pine Avenue West, McGill University, Montreal, QC H3A 1A2, Canada.
authors.forename: Willy
authors.initials: W
authors.lastname: Wynant
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.affiliation: Institute of Health and Human Development, UH250, Stratford Campus, University of East London, Water Lane, London E15 4LZ, UK.
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Netuveli
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, 1020 Pine Avenue West, McGill University, Montreal, QC H3A 1A2, Canada; Division of Cancer Epidemiology, Department of Oncology, 546 Pine Avenue West, McGill University, Montreal, QC H2W 1S6, Canada.
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Franco
authors.affiliation: Faculty of Dentistry, 2001 McGill College Ave, Suite 500, McGill University, Montreal, QC H3A 1G1, Canada. Electronic address: belinda.nicolau@mcgill.ca.
authors.forename: Belinda
authors.initials: B
authors.lastname: Nicolau
mesh_terms: D000368:Aged; D001114:Areca; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008409:Mastication; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology*; D017711:Nonlinear Dynamics; D012307:Risk Factors
keywords: Betel quid chewing; Dose-response; Nonlinearity; Oral cancer; Restricted cubic spline