Smoky Coal Exposure, Genetic Susceptibility, and Lung Cancer in Non-Smoking Women in China

Females in Xuan Wei County are almost all non-smokers, yet they have the highest lung cancer rate in China. Non-smoking women in Xuan Wei who use smoky coal in their home can inhale ten times higher levels of PAHs than a 20 cigarette per day active smoker, and air concentrations approach levels experienced by workers on the top-side of coke ovens. Several lines of research have provided strong support that the excess lung cancer in this region is caused primarily by PAHs derived from smoky coal exposure. As such, this region of China provides one of the best opportunities in the world to carry out a model study of gene-environment interactions in lung cancer. We have designed a hospital-based case-control study of 500 lung cancer cases and 500 controls among non-smoking women, with controls to be selected through a randomized recruitment design to achieve balance for the main effects of smoky coal exposure and ultimately greater power to detect interactions. The study will be carried out over a three-year period in Xuan Wei and Fu Yuan Counties in Yun Nan Province, China. In addition, we will be carrying out an exposure assessment study (n=150 households) to evaluate air and dermal exposure to PAHs from smoky coal use in order to model PAH exposure experienced by subjects in the case-control study. We will collect buccal cell, sputum, blood, and urine samples from all subjects. The primary goal of the study is to characterize genetic risk factors at the DNA level for lung cancer in this population and determine how they interact with smoky coal and PAH exposure. In addition, the hospital-based design will enable us to collect venous blood samples and cryopreserve lymphocytes, which will allow us to carry out state-of-the-art functional susceptibility assays such as testing ability to repair PAH-damaged DNA and apoptotic capacity, and to measure integrative markers of genomic stability such as telomere length and oxidative damage in mitochondrial DNA. These types of assays have never been conducted in this population and hold great promise to provide insights into cancer risk that will compliment those obtained by genotyping. This study will provide an important complement to and contrast with both DCEG and extramural studies of tobacco smoking and lung cancer, where unraveling the genetic component is challenging in part because hundreds of tobacco carcinogens in various combinations likely contribute.

• Cases: Life-long female residents of Xuan Wei and Fu Yuan Counties aged 18 to 79 years are considered the base population. Newly diagnosed primary female lung cancer cases (ICD-9 162), each diagnosis based on a minimum of clinical symptoms, chest X-ray, and a CT scan, will be identified at two hospitals in Xuan Wei County, one hospital in Fu Yuan County, and two hospitals in Qujing District.

Controls: Females alive during the study period who do not have lung cancer and who are residents of Xuan Wei or Fu Yuan Counties aged 18 to 79 will be eligible for recruitment into the study. Diagnosed conditions known to be unrelated to smoky coal exposure or air pollution will be eligible for inclusion into the study. Potential controls diagnosed during the current admission with any cancer or any of the following non-cancer conditions - (respiratory tuberculosis (ICD-10: A15, 16, 19, B90), respiratory infection (A31), neoplasm (C00-D48), ischaemic heart disease (I20-I25), arterial disease (I70-I73), respiratory disease (J00-J99), peptic ulcer (K25-K27), and respiratory symptoms (R04, R06, R09), will be excluded.