Abstract
Alcohol drinking and tobacco smoking are assumed to have significant independent and joint effects on oral cancer (OC) development. This assumption is based on consistent reports from observational studies, which, however, overestimated the independent effects of smoking and drinking, because they did not account for the interaction effect in multivariable analyses. This case-control study sought to investigate the independent and the joint effects of smoking and drinking on OC in a homogeneous sample of adults. Case patients (N = 1,144) were affected by invasive oral/oropharyngeal squamous cell carcinoma confirmed histologically, diagnosed between 1998 and 2008 in four hospitals of São Paulo (Brazil). Control patients (N = 1,661) were not affected by drinking-, smoking-associated diseases, cancers, upper aero-digestive tract diseases. Cumulative tobacco and alcohol consumptions were assessed anamnestically. Patients were categorized into never/ever users and never/level-1/level-2 users, according to the median consumption level in controls. The effects of smoking and drinking on OC adjusted for age, gender, schooling level were assessed using logistic regression analysis; Model-1 did not account for the smoking-drinking interaction; Model-2 accounted for this interaction and included the resultant interaction terms. The models were compared using the likelihood ratio test. According to Model-1, the adjusted odds ratios (ORs) for smoking, drinking, smoking-drinking were 3.50 (95% confidence interval –95CI, 2.76–4.44), 3.60 (95CI, 2.86–4.53), 12.60 (95CI, 7.89–20.13), respectively. According to Model-2 these figures were 1.41 (95CI, 1.02–1.96), 0.78 (95CI, 0.48–1.27), 8.16 (95CI, 2.09–31.78). Analogous results were obtained using three levels of exposure to smoking and drinking. Model-2 showed statistically significant better goodness-of-fit statistics than Model-1. Drinking was not independently associated with OC, while the independent effect of smoking was lower than expected, suggesting that observational studies should be revised adequately accounting for the smoking-drinking interaction. OC control policies should focus on addictive behaviours rather than on single lifestyle risk factors.
Highlights
Tobacco smoking and alcohol drinking are lifestyle risk factors which play an etiological role in oral cancer development with sufficient evidence
Such a high level of evidence is corroborated by a multitude of consistent observational studies published since the 709s, which reported that these lifestyle risk factors were significantly associated with oral cancer [1,2,3,4]
Pooled- and meta-analyses were designed to formally estimate the magnitude of this joint effect: two studies used the Multiplicative Interaction Parameter and found that the joint effect was three [6] and two [7] times greater than the individual effects of smoking and drinking multiplied by each other; another study investigated the Interaction Contrast Ratio and found that the joint effect was greater than the additive effect of both exposures by a factor of two [8]
Summary
Tobacco smoking and alcohol drinking are lifestyle risk factors which play an etiological role in oral cancer development with sufficient evidence. Such a high level of evidence is corroborated by a multitude of consistent observational studies published since the 709s, which reported that these lifestyle risk factors were significantly associated with oral cancer [1,2,3,4]. Subsequent observational studies reported that oral cancer risk in subjects exposed to both smoking and drinking was greater than additive It was higher than the sum of the two individual risks attributable to smoking alone and to drinking alone. Pooled- and meta-analyses were designed to formally estimate the magnitude of this joint effect: two studies used the Multiplicative Interaction Parameter and found that the joint effect was three [6] and two [7] times greater than the individual effects of smoking and drinking multiplied by each other; another study investigated the Interaction Contrast Ratio and found that the joint effect was greater than the additive effect of both exposures by a factor of two [8]
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