Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies

Abstract

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

Figure 1.

Odds ratios for pharyngeal cancer by categories of pack-years of cigarette smoking and number of cigarettes smoked per day (CPD), as well as fitted linear odds ratio models in pack-years. Bars, 95% confidence interval. Pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium were limited to never and current cigarette-only smokers.

Figure 2.

Estimated excess odds ratios per pack-year for cancers of the larynx, pharynx, and oral cavity within categories of cigarettes/day (square symbol) with 95% confidence intervals. Model 1 was fitted to all data (solid line) and to never and ≥10 cigarettes-per-day smokers (dashed line). Pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium were limited to never and current cigarette-only smokers.

Figure 3.

Odds ratios for pharyngeal cancer by categories of drink-years and number of drinks/day, as well as fitted linear odds ratio models in drink-years (drinks/day × years of consumption). Bars, 95% confidence interval. Pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium were for all pharyngeal cancer cases and controls.

Figure 4.

Estimated excess odds ratios per drink-year for cancers of the larynx, pharynx, and oral cavity within categories of drinks/day (square symbol) with 95% confidence intervals. Model 1 was fitted to all data (solid line) (upper panels) and to subjects consuming ≤10 drinks/day (dashed line). Pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium were for all pharyngeal cancer cases and controls.