Analysis of a historical cohort of Chinese tin miners with arsenic, radon,cigarette smoke, and pipe smoke exposures using the biologically based two-stage clonal expansion model

The two-stage clonal expansion model is used to analyze lung cancer mortali ty in a cohort of Yunnan tin miners based on individual histories with mult iple exposures to arsenic, radon, cigarette smoke, and pipe smoke. Advances in methodology include the use of nested dose-response models for the para meters of the two-stage clonal expansion model, calculation of attributable risks for all exposure combinations, use of both a fixed lag and a gamma d istribution to represent the time between generation of the first malignant cell and death from lung canter, and scaling of biological parameters allo wed by parameter identifiability. The cohort consists of 12,011 males worki ng for the Yunnan Tin Corporation, with complete exposure records, who were initially surveyed in 1976 and followed through 1988.,Tobacco and arsenic dominate the attributable risk for lung cancer. Of 842 lung cancer deaths, 21.4% are attributable to tobacco alone, 19.7% to a combination of tobacco and arsenic, 15.8% to arsenic alone, 11% to a combination of arsenic and ra don, 9.2% to a combination of tobacco and radon, 8.7% to combination of ars enic, tobacco and radon, 5.5% to radon alone, and 8.7% to background. The m odels indicate that arsenic, radon and tobacco increase cell division, deat h and malignant conversion of initiated cells, but with significant differe nces in net cell proliferation rates in response to the different exposures . Smoking a bamboo water pipe or a Chinese long stem pipe appears to confer less risk than cigarette use, given equivalent tobacco consumption. (C) 20 01. by Radiation Research Society.