User:Anthonyhcole/Squamous cell carcinoma of the esophagus

World cancer report
"encountered in individuals from low-resource regions"

"Squamous cell carcinoma of the oesophagus is characterized by great geographical variation. Pockets of high incidence (> 50 per 100 000 people) occur in the Islamic Republic of Iran (e.g. Golestan Province; > 100 per 100 000), parts of China (e.g. Linxian, Henan Province; > 130 per 100 000), and Zimbabwe. Intermediate incidence is seen in East Africa, southern Brazil, the Caribbean, much of China, parts of Central Asia, northern India, and southern Europe; incidence is low in North America, northern Europe, and western Africa. There are some data correlating ethnicity with the risk of squamous cell carcinoma, indicating that Turkish or Mongolian people in Central Asia and African Americans in North America are more likely than other people in those regions to be diagnosed with squamous cell carcinoma.

"Alcohol consumption and tobacco smoking and chewing are the strongest risk factors for the development of oesophageal squamous cell carcinoma, although these associations display marked geographical variation. Cessation of smoking substantially reduces the smoking-associated risk. Intake of hot beverages (hot maté in parts of South America; hot tea, hot coffee, or hot soups elsewhere) is similarly associated with risk of oesophageal squamous cell carcinoma, as is ingestion of caustic substances (such as occurs in suicide attempts and in accidental swallowing of household toxins by children). Certain dietary habits (low intake of fresh fruits and vegetables, fresh meat or fish, and dairy products, and high intake of barbecued meats and pickled vegetables, which may result in exposure to N-nitroso compounds) are associated with a high incidence of oesophageal squamous cell carcinoma. Use of opium, poor oral health, and poor nutrition all interact to affect outcome in oesophageal squamous cell carcinoma in high-risk areas. For example, in the Islamic Republic of Iran, opium intake is associated with poor outcome in univariate analysis but not in adjusted models [1]. Other circumstances mediating increased risk include having Plummer–Vinson syndrome (sideropenic dysphagia, including dysphagia due to oesophageal webs, glossitis, and iron-deficiency anaemia, usually in postmenopausal women), coeliac disease, and achalasia. Finally, exposure to ionizing radiation, often from treatment for breast carcinoma, is a risk factor."

"Given that alcohol consumption and tobacco use are the two major known causes of oesophageal squamous cell carcinoma, an Australian study assessed respective population attributable fractions based on 305 cases and 1554 controls. The results were 49% (95% confidence interval [CI], 38–60%) and 32% (95% CI, 25–40%) of oesophageal squamous cell carcinoma cases attributable to smoking and heavy alcohol consumption, respectively. More than 75% of the oesophageal squamous cell carcinoma burden in men could be attributed to smokers with heavy alcohol consumption [2]. Polymorphisms in acetaldehyde dehydrogenase 2 (ALDH2) are key to individual susceptibility to upper aerodigestive tract cancer; patients with inactive ALDH2 are at high risk of oesophageal squamous cell carcinoma [3]. In Asians, polymorphisms in the ALDH gene family are associated with altered risk of oesophageal squamous cell carcinoma. The effects of these polymorphisms are synergistic with alcohol consumption and smoking. In addition, the polymorphisms in ALDH associated with oesophageal carcinoma also result in accumulation of acetaldehyde, which causes flushing upon ingestion of alcohol (the “Asian flush”) in about one third of East Asians (Chinese, Japanese, and Koreans) [4]. Genome-wide association studies in Chinese individuals have identified several susceptibility loci, encompassing 5q11, 6p21, 10q23, 12q24, and 21q22 and including genes related to those encoding ALDH and thereby linked to the association between alcohol consumption and oesophageal squamous cell carcinoma in both Chinese and Japanese people [5,6]. The prevalence of oesophageal squamous dysplasia parallels rates of invasive oesophageal squamous cell carcinoma; it is typically found in 25% or more of adults older than 35 years in north central China, where the risk of this malignancy is among the highest in the world [7]."

Pathology and genetics
"Oesophageal squamous cell carcinoma is defined as a squamous neoplasm that invades through the epithelial basement membrane into the lamina propria, submucosa, muscularis propria, or deeper. Variable amounts of keratinization are seen, manifested by cells showing brightly eosinophilic opaque cytoplasm (Fig. 5.3.3A,B). Invasion into the lamina propria begins with the proliferation of rete-like projections of neoplastic squamous epithelium. Both horizontal and vertical spread are observed. Tumours can penetrate vertically through the oesophageal wall and invade the intramural lymphatic channels and veins.

"The development of oesophageal squamous cell carcinoma is understood to be a multistep process that progresses from normal squamous epithelium to include intraepithelial neoplasia (dysplasia; Fig. 5.3.3C) and culminates in the growth of invasive carcinoma. Mutation in the TP53 gene is an early event, sometimes detectable in intraepithelial neoplasia. Amplification of cyclin D1 occurs in 20–30% of these tumours. Inactivation of CDKN2A, either by homozygous deletion or by de novo methylation, appears to be associated with advanced disease.

"The scope of molecular analyses applicable to all tumour types is indicated from studies identifying alterations in genes, proteins, and microRNAs in oesophageal squamous cell carcinoma, of which 10 or more studies in each category are available. Epigenetic abnormalities are evident from DNA methylation, histone deacetylation, chromatin remodelling, gene imprinting, and non-coding RNA regulation studies [8]. High-throughput genotyping of metastatic tumours has identified phosphatidylinositol 3-kinase (PI3K) and BRAF mutations among the somatic mutations evident [9]. In a separate study, inactivating NOTCH1 mutations were identified in 21% of oesophageal squamous cell carcinomas from the USA but only rarely in such tumours from China [10].

"Familial predisposition to oesophageal cancer has been studied predominantly in association with focal non-epidermolytic palmoplantar keratoderma (also known as tylosis), a rare condition in industrialized countries (low-risk populations). This autosomal dominant inherited disorder of the palmar and plantar skin surfaces is associated with oesophageal cancer. The causative locus, the tylosis oesophageal cancer (TOC) gene, maps to 17q25, with missense mutations (c.557T → C [p.Ile186Thr] and c.566C → T [p.Pro189Leu]) in RHBDF2, which encodes the inactive rhomboid protease RHBDF2 (also known as iRhom2) [11].

Prospects
"The overall prognosis of oesophageal squamous cell carcinoma remains poor based on diagnosis of predominantly late-stage disease. Screening programmes to detect precursor and early-stage lesions have been implemented in some high-risk populations. Radiofrequency ablation therapy and other forms of endoscopic treatments appear promising for eradication of early lesions [12,13].

"Recently, variants in SLC39A6 were conclusively associated with survival in individuals with oesophageal squamous cell carcinoma"