Epidemiology of esophageal squamous cell carcinoma

LIU Yuan，WANG An-Hui，WANG Bo，ZHU Qing-Hao，SHANG Qing-Chao，LI Bo，HU Zhi-Hao，ZHANG Guan-Wen（Clinic of Xi’an Communication College，Xi’an 7006，China；Department of Epidemiology，School of Public Health，Cadet Brigade，Fourth Military Medical University，Xi’an 700，China）

·腫瘤流行病學與轉化醫學·

Epidemiology of esophageal squamous cell carcinoma

LIU Yuan1，WANG An-Hui2，WANG Bo2，ZHU Qing-Hao3，SHANG Qing-Chao3，LI Bo3，HU Zhi-Hao3，ZHANG Guan-Wen3（1Clinic of Xi’an Communication College，Xi’an 710106，China；2Department of Epidemiology，School of Public Health，3Cadet Brigade，Fourth Military Medical University，Xi’an 710032，China）

Esophageal cancer（EC）caused about more than 390 000 deaths in 2010．EC is the fourth leading cause of cancer death in China．Esophageal squamous cell carcinoma（ESCC）is the predominant histologic type in China．This study briefly reviews the epidemiology of ESCC，especially focus on the environmental and genetic risk factors of ESCC．

esophageal；carcinoma；squamous cell；epidemiology

Introduction

Esophageal cancer（EC）is one of the most common cancers and more than 482 000 new cases were diagnosed worldwide in 2008［1］，and caused about 395 000 deaths in 2010［2］．There are two main histological types of EC，esophageal squamous cell carcinoma（ESCC）and esophageal adenocarcinoma（EAC）．

ESCC distributed globally with varied incidence rate which is higher in certain area，especially in China，India and Iran．Based on the data from cancer cases reported to Ohio’s Cancer Registry 1998-2002，ESCC incidence in African-Americans was higher than that of whites［3］（5．0 versus 1．3 cases／100 000／year）．

ESCC is the predominant histologic type in China and in other areas with higher incidence of EC［4-5］．The incidence rate of EC（22．14 cases／100 000／year）ranked fifth in all cancer sites in China and the crude mortality of EC ranked fourth with rate of 16．77 cases／100 000／year［5］．The incidence rate and mortality rate of EC were higher in males than those in females，as compared to individuals living in urban areas those living in rural areas are at risk for EC．The overall age-specific incidence and mortality rates showed that both rates were relatively low before 45 years old．Long term mortality trends of ESCC in China was studied，and data showed that the overall decreasing trends in EC mortality were found in most Chinese people，aside from rural males［6］．

Occupational factors and ESCC

Studies［7-8］showed occupational hazards are important in the development of ESCC．Mortality of ESCC occurred more frequently among individuals exposed to silica dust and occupations potentially associated with exposure to silica dust and chemical solvents or detergents［7］．Farmer／gardener and workers with exposure to dust had a significant excess risk of ESCC in Taiwan［8］．

Tobacco use and alcohol consumption as main risk factors of ESCC

Tobacco use（tobacco smoking，tobacco chewing，etc．）is a predominant risk factor for ESCC．Alcohol drinking is more likely to increase the risk of ESCC．Both alcohol consumption and cigarette smoking are major risk factors in the development of ESCC．People exposed to both tobacco use and alcohol consumption have the risk of ESCC much more than those exposed to smoking or drinking alone．The risk of ESCC increased as the quantity of alcohol intake increased．The association between alcohol drinking and an increased risk of ESCC was more likely observed in Asian populations than in others［9］．Alcohol consumption and cigarette smoking are risk factors for ESCC in China and Japan［4，10-11］．

There isconsistentepidemiologic evidence for elevated risk of ESCC with alcohol consumption，and the risk increases with the amount of alcohol consumed．The association between light alcohol drinking（12．5 g／d）and risk of ESCC was reported［12］．The association was stronger in Asian areas than that in other area．Light alcohol intake（12．5 g／d）appears to be associated to ESCC mainly in studies in Asia，which suggests a possible role of genetic susceptibility factors．

A study revealed the odds ratio of ESCC to be 50．1 for those who were both heavy smokers and heavy drinkers in comparison to individuals who do not smoking and have no alcohol consumption［13］．Individuals，who are alcohol consumption with inactive ALDH2，are at high risk for ESCC．Carcinogenesis related to alcohol consumption and cigarette smoking and the mechanisms of ESCC were discussed［14］．

A meta-analysis study showed that there is a positive synergistic effect of alcohol and tobacco consumption on the risk of ESCC，either tobacco use or alcohol drinking was associated with a 20%-30%increased risk for ESCC compared with nonuser，but the use of both was associated with an approximately three fold risk for ESCC［15］．

Relationship between diet food and risk of ESCC

Fresh fruits，vegetables and antioxidants are associated with decreased risk of both ESCC and EAC［16-22］．Individuals with lower intake of fruits and vegetables had 2-fold increase in risk for both ESCC and ACE．Studies found intake of citrus fruit，raw fruits，vegetables and use of vitamin supplements is associated with the significant decrease risk of ESCC［17］．Dietary factors may contribute to different incidence of ESCC in the black versus white population of the United States［20］．

The relationship between the intake of processed meat and risk of ESCC has been explored．The intake of salted meat was associated with increased risk for ESCC（OR 3．82，95%CI 2．74-5．33）［21-22］．The intake of processed meat was associated with the increased risk for ESCC in Uruguay［21］．High intake of red meat and low consumption of poultry are associated with an increased risk of ESCC［22］．A case-control study in Huaian of China was conducted，and results showed that consuming acrid food，fatty meat，moldy food，salted and pickled vegetables，eating fast，were risk factors for ESCC［23］．A study in Kazak Autonomous Prefecture，Xinjiang，China found daily roasting meat consumption was related with the increased risk of ESCC and the methylation of p16 promoter was also related with daily roasting meat intake［24］．Areca nut chewing was significantly and independently associated with an increased risk of ESCC in Asians［25］．High-temperature cooking and frying were found to be associated with increased risk of ESCC in Southern Iran［26］．

Animal contact，oral hygiene，socioeconomic status and other factors

Long-term and daily close contact with animals was associated with increased risk for ESCC in Kashmir，India，area［27-28］．Contact with ruminants was associated with an eightfold increase in risk of ESCC［28］．A study in Kashmir found an inverse association between tooth cleaning and the risk of ESCC［29］．Poor oral hygiene was associated with the risk for ESCC［30］．The inverse association between cleaning teeth and ESCC was stronger with using brushes than with using sticks／fingers．Low socioeconomic status（SES）and strenuous physical activity were significant associated with the risk of ESCC in the Kashmir valley［31］．

Infection factors

The relationship between HPV infection and the risk for ESCC was discussed［32-39］．Results of systematic reviews and meta-analysis indicated that the average prevalence of HPV infection was varied from 17．6%to 32．2% accordingto the differentdetecting methods［32-33，35-36］．HPV infection has been observed in about one-third of EC patients in Asia and South Africa．HPV was not an independent risk factor for ESCC in nonsmokers and nondrinkers；however，HPV was associated with increased risk for ESCC in smokers［39］．

Genetic susceptibility of ESCC

Human genomeepidemiologyprovidesagreat chance for epidemiologists and clinical scientists to explore the cause of ESCC and evaluate genomic biomarkers for diagnosis or prognosis［40］．The technique of microarray chips used in genome-wide association studies（GWAS）provides the possibility to compare millions of SNPs between genome from cases and controls．More and more studies use GWAS methods to analyze the relationship between genomic variants and ESCC．

Genomic variants（Table 1）identified to be associated with ESCC［41-58］．Some of those genetic variants were confirmed in other populations and some others were not identified in other populations．GWAS in China showed that variants in several chromosome regions conferred an increased risk of ESCC，but only genetic variants in alcohol-metabolizing genes were risk factors for ESCC in Japanese［4］．A molecular mechanism of ethanol-associated ESCC was discussed［41］．A 2-step GWAS including 1070 cases and 2836 controls identified that single nucleotide polymorphisms （SNPs） rs671，rs1229984，alcohol consumption，and tobacco use were risk factors for ESCC［43］．

MicroRNAs（miRNAs）have been involved in initiation and development of ESCC［59-60］．The levels of miR-145 and miR-143 were decreased in ESCC tissues．An inverse association between miR-143 expression levels and cancer invasion or metastasis was identified［59］．Results showed that miR-143 may act as a suppressor in the process of ESCC．MiR-10a and MiR-205 were observed as potential specific biomarkers for ESCC［60］．

In conclusion，Epidemiological studies of ESCC will explore the genomic variants affecting signaling，epigenetic regulation，RNAs，proteins and pathways as well as environmental risk factors involved in the process of ESCC．

Table 1 Genomic variants identified to be associated with ESCC［40］

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2095-6894（2017）05-25-04

2017-04-04；接受日期：2017-04-20

國家自然科學基金面上項目（81072353）；陜西省社會發展公關項目（2016SF-086）

劉 媛．本科，主管護師．E-mail：liuyuandonna＠hotmail．com

王安輝．博士，副教授．E-mail：wanganhui＠hotmail．com