1. Introduction

Our body obtains nutritional supplies from the environment through two primary pipes: bronchus and esophagus, the two simplest organs in the respiratory and digestive systems, respectively. While the bronchus passes oxygen to the lung and expels carbon dioxide out of our biological system, the esophagus transports water and food into the stomach from where a sophisticated process of digestion and nutrient extraction begins.

Although skin cancer might be the most common malignancy in the world, accounting for at least 40% of all cancer cases [1], it is usually excluded from the annual cancer report due to its least perniciousness. The remainders are mostly found in the respiratory and digestive systems, particularly in the digestive system, which hides about twice as much cancer as found in the respiratory system. Five of the top 10 deadliest cancers take place in the digestive organs, including stomach, liver, colon, pancreas, and esophagus. Esophageal cancer is ranked as No. 6 on the list. While the incidence of most cancers is declining year by year, esophageal cancer continues climbing as the fast growing malignancy in the world. Based on a recent prediction, by the year of 2035, the global population of the esophageal cancer patients will be up by 77.4% [2]. In some regions of Asia, Africa, and the South America, the numbers could be doubled in less than 20 years. Logically, esophageal malignancy will very likely become one of the top global concerns in the near future.

The human esophagus is just a short tube of ~25 cm, separating from the rest of the body by two muscular rings at the ends, the upper esophageal sphincter and the lower esophageal sphincter, which control the flow of ingested materials from the mouth to the stomach. Like a corridor that sends visitors from the gate to the main building, the esophagus sends food from the mouth to the stomach. It is a rather simple structure, but, because of its critical location, any abnormalities associated with this organ can be devastating.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

When food is being swallowed, the upper sphincter relaxes, allowing food to enter the pipe. Peristaltic contractions of the esophageal muscle push the food down through the lower sphincter into the stomach. Besides controlling the amount of swallowed food going down into the stomach, the lower esophageal sphincter also works like a dam sitting in between the esophagus and the stomach to prevent the stomach contents to back up into the esophagus. When this muscular structure does not hold well, gastroesophageal reflux disease (GERD) occurs, in which case stomach acid mixed with duodenal content flows back into the esophagus. If this happens frequently enough, it leads to esophagitis, and then to Barret's esophagus, a premalignant metaplasia of the esophageal lining changing from stratified squamous epithelium to simple columnar epithelium. Compared to normal people, individuals with Barret's esophagus can have as high as a 400-fold increased risk to develop esophageal cancer [3].

While the use of tobacco and alcohol together has been the main risk factor for ESCC, obesity and low vegetable consumption increase the chances to develop EAC. In the obese community, the excessive body weight puts constant pressure on the stomach and causes frequent acid reflux. These highly acidic fluids regurgitated from the stomach or even from the duodenum induce inflammation in the esophagus. As the episodes continue, the epithelial lining of the esophagus gradually transforms from stratified squamous epithelium to intestinal columnar phenotype for adaptive protection, as the latter is more endurable to acidic insults. Unfortunately, however, this metaplasia confers a greater danger to become malignant. Studies have shown that people with this kind of esophageal adaptation could have 400 times more likelihood to develop EAC than the general population [8]. Insufficient uptake of fresh fruits and

Introductory Chapter: Esophagus and Esophageal Cancer

http://dx.doi.org/10.5772/intechopen.77995

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Although both ESCC and EAC take place in this short organ, they are very different cancers. From an epidemiological point of view, there is only one common feature between ESCC and

In addition to the factors associated to life habits, there are also genetic elements contributing to esophageal cancer development. The genomic analysis reveals distinct profiles between ESCC and EAC. ESCC is more similar to squamous cell carcinoma of the head and neck than

ESCC is believed to develop from basal cell hyperplasia and dysplasia. During this process, the main mutation pattern is C to A substitution, which is commonly found in smokers [9]. The most frequently mutated genes include TP53 (p53, tumor suppression transcription factor), CDKN2A (p16, cyclin-dependent kinase inhibitor), KDM6A (histone demethylase), KMT2D (lysine methyltransferase), and RB1 (retinoblastoma-associated protein). On the other hand, some genes are highly expressed, such as CCND1 (cyclin D1), TP63 (tumor protein), SOX2 (sex-determining region Y), MYC (c-myc), FGFR1 (fibroblast growth factor receptor), TNFAIP3 (tumor necrosis factor-induced protein), and CHN (chimerin) [10]. Table 1 lists the top five

EAC, on the other hand, is generally believed to originate from Barret's esophagus, an esophageal metaplasia in response to chronic acid reflux. During this process, esophageal epithelium transforms from a multilayer of squamous epithelial cells to a single layer of intestinal columnar epithelial cells, or like the metaphor used by Ahrens et al.: "turning skyscrapers into townhouses" [14]. The natural question is where the columnar cells come from. There are four theories currently to explain the origin of esophageal columnar cells: (1) true transdifferentiation of the esophageal squamous cells, (2) trans-commitment of the esophageal stem cells, (3) colonization and subsequent trans-commitment of bone marrow stem cells, and (4)

The first theory is supported by the fact that the esophagus derives from the columnar epithelial cells initially during embryonic development and later is replaced by squamous

EAC, and that is both preferring men over women, while differences are a lot greater.

to EAC, while the latter has more resemblance to gastric adenocarcinoma.

genes frequently mutated and the top five highly expressed.

replacement by gastric columnar epithelial cells.

vegetables can also create this type of drama.

3. Genetics of esophageal cancer
