Esophageal cancer (EC) is the 8th
most common incident cancer in the world and, because of its high fatality rate, ranks 6th
among all cancers in mortality [1
]. It is not surprising, therefore, that the etiology of EC has been investigated for over a century. Based on clinical observations, Craver in 1932 and Watson in 1939 list excessive use of alcohol and tobacco, low socioeconomic status, poor oral health, and consumption of hot drinks as risk factors for EC [3
]. They also cite papers on EC etiology published decades earlier. For example, Craver cites a 1920 article from Argentina that suggests maté drinking as a risk factor for EC.
Etiology of EC differs by histology. EC can be histologically classified into two main types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). These two cancer types differ not only histologically, but also with respect to their incidence trends, populations that they affect, and risk factors. One could call EA “an emerging disease”. Until the 1970s, ESCC constituted the large majority (over 90%) of all EC cases in all parts of the world. Since then, however, incidence rates of EA have sharply increased in many countries in the Western World [5
], so that this cancer type now constitutes approximately half of all EC cases in some Western countries. In contrast, ESCC continues to be the dominant type in the rest of the world.
Most etiological studies conducted before the 1980s did not distinguish between ESCC and EA, but their results were mainly relevant to ESCC, because EA was uncommon before then. Also, results of the more recent studies from Asia, South America, or Africa that do not report histology are mainly applicable to ESCC because EA is still relatively uncommon in these areas [10
]. Extensive investigations into the etiology of EA started only in the 1990s, mainly in Western countries, where larger numbers of this cancer began to be diagnosed.
Some parts of the world have distinct epidemiologic patterns of ESCC. In most parts of the world, incidence rates of ESCC, adjusted to the 1970 World Population, are lower than 15/105
person-years and ESCC is 2–3-fold more common in men than in women [13
]. However, in certain areas of China (in the Taihang mountain region) and Iran (in Golestan Province), a completely different pattern is observed: incidence rates above 100/105
person-years have been reported, and men and women have similar incidence rates [13
]. As we shall see below, ESCC risk factors in these areas may be different from those seen elsewhere. For example, unlike almost everywhere else, tobacco smoking and alcohol consumption play a minor role [14
ESCC and EA have known precursor lesions, esophageal squamous dysplasia (ESD) and Barrett’s esophagus (BE), respectively. Compared to subjects with no ESD, those with mild, moderate and severe ESD have an increased risk of ESCC of approximately 3-, 10- , and 30-fold, respectively [16
]. Presence of BE substantially increases EA risk; risk of progression to EA is 0.5 – 1% per year [17
]. Therefore, ESD and BE have been used as surrogate endpoints for ESCC and EA, respectively.
With this background, we review some factors that increase or decrease EC risk. Where data are available, we discuss the effect of each factor separately for ESCC and EA. Many factors have been investigated in relation to EC, among which we have chosen those that are established risk factors, or those for which there is substantial data, or those for which there is currently strong research interest. These factors include habits (tobacco use, alcohol consumption, opium consumption, maté drinking, consumption of hot drinks, consumption of carbonated soft drinks, eating pickled vegetables), nutritional deficiencies (low intake of fresh fruit and vegetables, vitamin and mineral deficiencies), medications (non-steroidal anti-inflammatory drugs, medications that relax lower esophageal sphincter, H2 receptor antagonists), infections (Helicobacter pylori, Human papillomavirus), chemical carcinogens (polycyclic aromatic hydrocarbons, nitrosamines, acetaldehyde), physiologic or pathologic predisposing conditions (gastroesophageal acid reflux, hiatal hernia, achalasia, gastric atrophy, poor oral health), occupational exposure (to silica and asbestos), and low socioeconomic status ().
Environmental risk factors and predisposing conditions for esophageal cancer