Siliceous spicules in food and esophageal squamous cell carcinoma in northern China

Abstract

Certain regions near the Taihang Mountain in northern China continue to experience a persistently high prevalence of esophageal squamous cell carcinoma (ESCC), despite decades of research and interventions targeting established risk factors. The previous study unveiled siliceous fragments in the tumor tissue of ESCC patients in this region, resembling prickle hairs on wheat surfaces. This observation led to a hypothesis that the wheat-derived siliceous spicule is a risk factor that sheds new light on the persistently high incidence of ESCC in northern China. Thus, the motivation of this thesis is to revitalize the stagnant exploration of ESCC etiology, by turning to wheat-derived siliceous spicules, a little-explored clue that may help illuminate the roots of the enduring ESCC burden in northern China. For this glass-root hypothesis of ESCC, this thesis mainly has three aims: 1) to investigate primary dietary exposure vehicle of siliceous spicules to humans in northern China; 2) to identify the plant-specific source of siliceous spicules and the entering pathway into human diet; 3) to evaluate the impact of ingesting siliceous spicule-contaminated diets on esophageal tumor via animal models. Firstly, wheat flour, a major staple food in northern China, was found to be contaminated by siliceous spicules, and the highest level of siliceous spicule contaminant and longer fiber length were highlighted in the wheat flour from the ESCC-endemic area. Then, siliceous outgrowths on the palea and lemma of wheat husks, located close to kernels, were identified as the major source of siliceous spicules. During wheat flour preparation, the shedding siliceous outgrowths were found to be retained with kernels until the washing step. The unrigorous washing practice, indicated by reduced washing cycles and water-saving methods, a common condition in arid ESCC-endemic areas, was one pathway for siliceous spicules entering into flour because the siliceous spicule contaminants could not be efficiently removed. At last, incorporating the siliceous spicule-enriched wheat husk diet into animal feed to mimic a siliceous spicule-contaminated diet, it was found that ingesting the siliceous spicule-contaminated diet potentially promotes tumorigenesis and induces inflammatory changes in the esophageal microenvironment. In summary, the findings of this thesis are that wheat husk (palea and lemma)-derived siliceous spicules contaminate wheat flour via unrigorous grain washing practices under water scarcity, and ingesting of siliceous spicule-contaminated diet possibly promotes tumor and induces inflammation in the esophagus as revealed in rats. This thesis takes a step forward in uncovering wheat-derived siliceous spicules as a potential risk factor for ESCC. It is also expected to offer a fresh lens to examine why some regions, despite sharing similar diets and genetics, bear a heavier disease burden. The findings may suggest practical directions for agriculture and public health, and prompt more attention to the invisible contaminants that may lie hidden in food.