Identifying Cancer-Susceptible Individuals in a Radon-Exposed Population

摘要

Lung cancer now accounts for 30% of all cancer deaths annually in the United States. Approximately 170,000 new cases of lung cancer are diagnosed each year, and the 80% mortality rate associated with this disease makes it a significant public health burden. Despite intensive efforts in chemotherapeutic and radiotherapeutic intervention, 5-year survival rates have not increased dramatically over the past 25 years. Survival could be improved if noninvasive screening procedures are developed to detect alterations in critical regulatory genes that prove prognostic for lung cancer. These procedures would facilitate the identification of early lung cancers that are more amenable to curative surgical resection. Smoking is estimated to be the cause of 85% of lung cancer mortality. Exposure to other environmental and occupational respiratory carcinogens may interact with cigarette smoking or be carcinogenic themselves at high doses. At sufficiently high concentrations, radon (~(222)Ra) and its α-particle-emitting decay products polonium-214 and polonium-218 cause an excess of lung cancers in smokers and never-smokers who mined uranium. Studies undertaken to quantify risk using uranium miners concluded that a model intermediate between an additive and multiplicative relationship best described lung cancer risk from exposure to tobacco and radon. This high-risk population is ideal for identifying and validating genetic and epigenetic alterations as biomarkers for detecting early cancer.