The great majority of the EC cases are ESCC and EAC which are making 95% of all EC cases. Among these two most common types ESCC is more prevalent in under-developed countries and EAC is prevalent in developed countries (10, 11). However, the ESCC remains the most common histologic subtype of EC worldwide (12). Since the esophagus is lined by squamous epithelium, it could be a reason ESCC is more predominant. Moreover, other risk factors are also having important role. In our study the predominant subtype was ESCC (68%).
EC occurs mostly in older age groups. The risk rises with age, with an average age of 67 years at diagnosis (13). In our study the mean age of case groups was 59.4 years old compared to mean age of control (48 years). Study in India (14),Tanzania (15) and China (16) reported the majority of EC cases occurred in age group of > 60 years, > 65 years, and 60–69 years, respectively. Although EC occurs in the older age groups the lowest age for EC in the present study is 30 years. Study in more endemic area for EC, such as China, Japan and Iran also reported that EC starting from 30 years old age onward (17). The likely reason why EC occurs in older age maybe due to increase in the exposure to environmental risk factors and certain specific genes that are more likely to be altered and mutated by increasing age.
The EC most commonly affect males than female population. The incidence of EAC is 6–10 times higher in male than female and the incidence of ESCC is 2–3 times higher (18). In our study most of the EC cases were in males and showed 3.3-time associated risk of EC in male groups. Similar distribution were reported by study was conducted in Tanzania (15), an ecological study, which conducted based on GLOBOCAN project of World Health Organization (WHO) for Asian counters estimated that 70.33% incidence of EC cases in male and 29.87% in female (19). In addition, American Society of Cancer (20) and cancer research from United Kingdom (UK) countries reported the higher incidence of EC in male over female (21). Equally or higher distribution of EC among females is a rare epidemiologic feature of EC which is reported in Linxian, China. This may show a single, very powerful risk factor shared by both genders (22). By the reviewing of literatures, it was not clear why the EC cases occur more in male than female, but probably due to the exposure to different environmental factors. As, the EC most common in farmers and workers in agricultures as men commonly do these works in rural areas. Others risk factors such as smoking, alcohol consumption and snuff dipping are also common among males.
The current study showed belonging to low SES comparing to middle/high SES, has the higher associated risk with EC (OR = 14.08). In addition, according to the education level, participants who were illiterate/having primary school education comparing to those who studied up to high school or more are at higher risk of EC (OR = 11.21). Many studies and different countries reported low SES and low education are related to the increase incidence of EC. Study was obtained in India indicated that 30.91% of EC patients were illiterates, 73.91% patients belonged to lower SES (23). Case control studies are conducted in Chinese and Iranian population sample revealed strong association between low SES and an increased risk of EC (24, 25). Low SES and increases the risk of EC incidences, are also reported in developed countries than might be expected. A case-control analysis in the United States by Gammon et al. estimated that the risk of EC among those with low income and low education was higher (26). The correlation of low SES and EC was documented by a case control study in Sweden, the unqualified employees were at 3.7 times the risk of AC and 2.1 times the risk of ESCC (27). Low education has also had negative impact on the prognosis and survival rate of the EC. In this regard a cohort study in Sweden reveals clear association between lower education and increased mortality after esophagectomy of EC patients (28).
Very large number of the EC patients in current study were living in rural areas (92.4%) and suggest an increased associated risk of EC among people living in rural areas (OR = 25.16). This findings are in line with study has been conducted in Turkey and reported the association of EC and rural population (p < 0.001) (29) and study in India also showed high prevalence of EC in rural areas (30).
Despite, the occupation did not show significant association with risk of EC in multivariate model in our study, but the majority of the EC patients were unemployed (93.9%). Of these unemployed EC patients 75% were farmer and all female EC patients were housewives. Studies in Brazil and Iran reported the that EC was more prevalent in farmers in high prevalent areas (25, 31). The work environment in agriculture is complex, with many potential hazardous exposures, such as pesticides, herbicides, fertilizers, dusts, zoonotic microbes, and sunlight (32). The reason why it is not significant in our study, will be belongs to small sample size and this need larger and wide study on this class population.
Weight and height did not show statistically significance association with EC in our study. A meta-analysis study showed high risk of obesity with EAC but inverse association to ESCC (33). Another study in Netherland also showed significant association between obesity and overweight with EC (34). No significance of EC and body mass index (BMI) in our study is because all cancer patients had the weight loss during the time of the diagnosis of the cancer.
In addition to environmental risk factors, hereditary susceptibility in esophageal carcinogenesis is another noticeable risk factor. Meanwhile, the co-occurrence of EC in family members is not always related to hereditary susceptibility but it also be consider as environmental factors (35). A study by Chen et al (36), reported that EC patients with positive family history increased 2-fold risk of developing of EC, while for whose both parents had history of cancer, 8-fold risk had been observed. Another study in high endemic area of the Iran showed more than 2-times risk for people who had positive first-degree family history of the cancer (37).
In the present study, the same association between family history of cancer in first degree family and EC was identified (OR = 4.71). The specific genetic expression related to EC in Afghanistan, however, have not been researched yet, which is important in prevention and treatment of EC. However, a multi-center case-control study in USA revealed no statistically significant risk of positive family history with EC (38). The inconsistency in the result from different articles might be due to different genetic susceptibility and different type environmental risk factors exposures.
To the best of our knowledge, this is the first study in Afghanistan in case control design which estimate the associated risk factors with EC. The study has been conducted in one of the main pathology centers of the country which receive biopsy samples from all around the country.
The limitations of this study includes small sample size due to the limited number of oncology center in the country. Secondly due to a smaller number of the EC cases in particular EAC cases, we were not able to run statistical analyses for both subtypes of EC separately. Thirdly, the risk factors are not studied in details because this is the first research assessing the risk factors in Afghanistan.