title: Combined effect of tobacco smoking and alcohol drinking in the risk of head and neck cancers: a re-analysis of case-control studies using bi-dimensional spline models.
abstract: The synergistic effect of tobacco smoking and alcohol consumption on the risk of head and neck cancers has been mainly investigated as a cross-product of categorical exposure, thus leading to loss of information. We propose a bi-dimensional logistic spline model to investigate the interacting dose-response relationship of two continuous exposures (i.e., ethanol intake and tobacco smoking) on the risk of head and neck cancers, representing results through three-dimensional graphs. This model was applied to a pool of hospital-based case-control studies on head and neck cancers conducted in Italy and in the Vaud Swiss Canton between 1982 and 2000, including 1569 cases and 3147 controls. Among never drinkers and for all levels of ethanol intake, the risk of head and neck cancers steeply increased with increasing smoking intensity, starting from 1 cigarette/day. The risk associated to ethanol intake increased with incrementing exposure among smokers, and a threshold effect at approximately 50 g/day emerged among never smokers. Compared to abstainers from both tobacco and alcohol consumption, the combined exposure to ethanol and/or cigarettes led to a steep increase of cancer risk up to a 35-fold higher risk (95 % confidence interval 27.30-43.61) among people consuming 84 g/day of ethanol and 10 cigarettes/day. The highest risk was observed at the highest levels of alcohol and tobacco consumption. Our findings confirmed a combined effect of tobacco smoking and alcohol drinking on head and neck cancers risk, providing evidence that bi-dimensional spline models could be a feasible and flexible method to explore the pattern of risks associated to two interacting continuous-exposure variables.
authors: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini, 2, 33081, Aviano, PN, Italy.
authors: Luigino
authors: L
authors: Dal Maso
authors: Department of Economics, Business, Mathematics and Statistics, University of Trieste, Trieste, Italy.
authors: Nicola
authors: N
authors: Torelli
authors: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini, 2, 33081, Aviano, PN, Italy.
authors: Elisa
authors: E
authors: Biancotto
authors: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini, 2, 33081, Aviano, PN, Italy.
authors: Matteo
authors: M
authors: Di Maso
authors: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini, 2, 33081, Aviano, PN, Italy.
authors: Andrea
authors: A
authors: Gini
authors: Division of Radiation Oncology, CRO Aviano National Cancer Institute, IRCCS, Aviano, Italy.
authors: Gianni
authors: G
authors: Franchin
authors: Cancer Epidemiology Unit and Vaud Cancer Registry, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors: Fabio
authors: F
authors: Levi
authors: Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors: Carlo
authors: C
authors: La Vecchia
authors: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini, 2, 33081, Aviano, PN, Italy.
authors: Diego
authors: D
authors: Serraino
authors: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini, 2, 33081, Aviano, PN, Italy. polesel@cro.it.
authors: Jerry
authors: J
authors: Polesel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000453:epidemiology; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D006258:Head and Neck Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013557:Switzerland / Q000453:epidemiology
keywords: Alcohol intake; Dose–response relationship; Head and neck cancers; Spline models; Tobacco smoking