Alcohol and Head and Neck Cancer: Updates on the Role of Oxidative Stress, Genetic, Epigenetics, Oral Microbiota, Antioxidants, and Alkylating Agents.

Giampiero Ferraguti,Alessandro Mattia,Christian Barbato,Brunella Caronti,Marco Fiore,Antonio Greco,Maria Grazia Di Certo,Enzo Agostinelli,Giammarco Raponi,Marco De Vincentiis,Antonella Polimeni,Antonio Minni,Mauro Ceccanti,Sergio Terracina,Luigi Tarani,Carla Petrella,Marco Lucarelli,Massimo Ralli

doi:10.3390/antiox11010145

Abstract

Head and neck cancer (HNC) concerns more than 890,000 patients worldwide annually and is associated with the advanced stage at presentation and heavy outcomes. Alcohol drinking, together with tobacco smoking, and human papillomavirus infection are the main recognized risk factors. The tumorigenesis of HNC represents an intricate sequential process that implicates a gradual acquisition of genetic and epigenetics alterations targeting crucial pathways regulating cell growth, motility, and stromal interactions. Tumor microenvironment and growth factors also play a major role in HNC. Alcohol toxicity is caused both directly by ethanol and indirectly by its metabolic products, with the involvement of the oral microbiota and oxidative stress; alcohol might enhance the exposure of epithelial cells to carcinogens, causing epigenetic modifications, DNA damage, and inaccurate DNA repair with the formation of DNA adducts. Long-term markers of alcohol consumption, especially those detected in the hair, may provide crucial information on the real alcohol drinking of HNC patients. Strategies for prevention could include food supplements as polyphenols, and alkylating drugs as therapy that play a key role in HNC management. Indeed, polyphenols throughout their antioxidant and anti-inflammatory actions may counteract or limit the toxic effect of alcohol whereas alkylating agents inhibiting cancer cells’ growth could reduce the carcinogenic damage induced by alcohol. Despite the established association between alcohol and HNC, a concerning pattern of alcohol consumption in survivors of HNC has been shown. It is of primary importance to increase the awareness of cancer risks associated with alcohol consumption, both in oncologic patients and the general population, to provide advice for reducing HNC prevalence and complications.

Highlights

Worldwide, head and neck cancer (HNC) accounts for more than 890,000 cases and450,000 deaths annually [1]
Even though more than 90% of Head and neck cancer (HNC) overexpress epidermal growth factor receptor (EGFR), which is associated with high local recurrence rate and poor survival, only a modest subgroup of HNCs shows amplified copy numbers or mutational activation of the EGFR gene, suggesting the existence of other mechanisms acting downstream on the pathways [123]
It has been proposed that, regarding HNCs, alcohol might enhance the exposure of epithelial cells to carcinogens, but a variety of pathophysiological biomechanisms have been linked to the direct or indirect tumorigenic effects of alcohol [121,172]

Summary

Introduction

Head and neck cancer (HNC) accounts for more than 890,000 cases and450,000 deaths annually [1]. Head and neck cancer (HNC) accounts for more than 890,000 cases and. Together with tobacco smoking, and human papillomavirus (HPV) infection (Table 1) are HNC-recognized risk factors [23,24,25,26]. The role of alcohol in HNC seems to be broader than that of a simple risk factor, as suggested from recent findings which highlighted how significant inverse association exists between alcohol drinking and prognosis among HNC patients [27,28]. The proportion of HNC cases attributable to alcohol is still increasing, emphasizing the importance of alcohol consumption limitation to prevent HNC. Alcohol use among HNC survivors negatively impacts patient outcomes and is an important risk factor for recurrent and second primary tumors

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