Objective: The overall goal of this project is to determine whether polycyclic aromatic hydrocarbons (PAHs) are contributing to the high rate of esophageal cancer (EC) in Linxian, China. Specific objectives are to 1) evaluate short-term (24 hour) PAH exposure by measuring l-OH-Pyrene glucuronide levels in urine samples, 2) evaluate long-term (120 days) PAH exposure by measuring hemoglobin DNA adducts in blood samples, 3) evaluate the level of ingested PAHs by measuring benzo(a)pyrene (B[a]P) levels in food samples, 4) identify characteristics of the regional coal that may be associated with increased carcinogenesis, 5) identify associations between specific environmental exposures and the biologically detected levels of PAHs with a short environmental questionnaire, and 6) use the results of this pilot study to help design a more comprehensive environmental and biological monitoring study. Background: EC is one of the most fatal cancers worldwide, with Linxian having one of the highest rates in the world. In this high risk region several etiologic possibilities, including nutritional deficiencies, fermented, and moldy foods and the inhalation of PAHs, have been considered, however, none has been convincingly linked to the high rate of EC. PAHs, such as B[a]P, are formed during the incomplete combustion of soft coal. The inhabitants of Linxian use soft coal extensively in unvented dwellings for cooking and heating. The carcinogenic potential of PAHs has been well described, including a two-year feeding study in mice that identified a striking dose-response relationship between B[a]P food levels and EC incidence and several human studies showing an association of high level environmental PAH exposure with an increased incidence of lung and gastrointestinal cancers. In addition, results from a preliminary evaluation show high-levels of B[a]P in raw and processed corn and wheat food samples, the major dietary component of Linxian, thus providing evidence that high levels of PAHs are being ingested. Methods: To assess the association of PAHs with Linxian's high rate of EC, we plan to analyze urine, blood, food, and coal samples and administer an environmental questionnaire. The participants will include two of the oldest individuals (a male and a female greater than eighteen years of age) from each of 10-15 nonsmoking households from the high risk region of Linxian and appropriately age matched controls from a total of 20 nonsmoking individuals from a low risk region. Progress: To date, we have accrued 41 patients from this high risk region and a low risk region in China. During the period covered we completed the urine 1-hydroxypyrene ananlysis and the organic geochemical analysis of the coal. We have also initiated plans to analyze the urine samples for aflatoxins, including fumonisin and deoxynivalenol. Preliminary analysis suggests that we will be able to assess the level of PAH exposure in this high risk region and evaluate the effectiveness of the methods used in this pilot study.
