Association of Nitrogen Compounds in Drinking Water with Incidence of Esophageal Squamous Cell Carcinoma in Shexian, China

Abstract

The incidence of esophageal squamous cell carcinoma (ESCC), which is the eighth most common malignancy worldwide, is highest in China. The purpose of this study was to investigate the association between nitrogen compounds in drinking water with the incidence of ESCC by geographical spatial analysis. The incidence of ESCC is high in Shexian county, China, and environmental factors, particularly nitrogen-contaminated drinking water, are the main suspected risk factors. This study focuses on three nitrogen compounds in drinking water, namely, nitrates, nitrites, and ammonia, all of which are derived mainly from domestic garbage and agricultural fertilizer. The study surveyed 48 villages in the Shexian area with a total population of 54,716 (661 adults with ESCC and 54,055 non-cancer subjects). Hot-spot analysis was used to identify spatial clusters with a high incidence of ESCC and a high concentration of nitrogen compounds. Logistic regression analysis was used to detect risk factors for ESCC incidence. Most areas with high concentrations of nitrate nitrogen in drinking water had a high incidence of ESCC. Correlation analysis revealed a significant positive relationship between nitrate concentration and ESCC (P = 0.01). Logistic regression analysis also confirmed that nitrate nitrogen has a significantly higher odds ratio. The results indicate that nitrate nitrogen is associated with ESCC incidence in Shexian county. In conclusion, high concentrations of nitrate nitrogen in drinking water may be a significant risk factor for the incidence of ESCC.

Epidemiology of Esophageal Cancer in Japan and China

“…It is highly likely that nitrosamine and its precursors are very strong risk factors. 39 Although evidence from ecologic studies suggests a correlation between nitrosamine precursors and ESCC incidence, 40 , 41 very few studies have measured nitrosamine and its precursors and evaluated their associations with esophageal cancer risk. The main challenge for such studies is correctly determining exposure to nitrosamine from various sources, including exogenous exposure and endogenous formation.…”

“…Earlier studies found high concentrations of nitrates and nitrites, the precursors of nitrosamine, in drinking water samples, and nitrosamine in food samples. 39 Two ecologic studies, 1 conducted in Cixian 40 and the other in Shexian, 41 found that high concentrations of nitrate nitrogen in well water correlated with ESCC incidence. These findings highlighted the possible role of high levels of nitrate exposure in the pathogenesis of ESCC in high-risk areas.…”

Prevalence and Age, Gender and Geographical Area Distribution of Esophageal Squamous Cell Carcinomas in North China from 1985 to 2006

“…The previous studies (Wang et al, 2007;Zhang et al, 2012;Dar et al, 2013;Hakami et al, 2013) have suggested that living in rural area is a risk factor for ESCC, as there are worse socioeconomic level, and more unhealthy eating habits. However, the exact statistical difference in prevalence of ESCC between urban and rural areas are not mentioned in these studies.…”

4-Methylthio-3-butenyl isothiocyanate (raphasatin) exerts chemopreventive effects against esophageal carcinogenesis in rats

“…Epidemiological studies have shown that tobacco smoking, excessive alcohol consumption, and eating pickled vegetables are associated with increased risk of ESCC; these habits can lead to the endogenous generation of nitrosamines, a common type of carcinogen 5 . Furthermore, high concentrations of nitrate nitrogen, the precursor of nitrosamine, in drinking water can increase the risk of ESCC 6 . In contrast, the consumption of fruits and vegetables has been shown to be associated with a reduced risk of ESCC 7 , 8 .…”