Suresh Moolgavkar

..We quantified the cumulative impact of changes in smoking behaviors that started in the mid-1950s on lung cancer mortality in the United States over the period 1975-2000...

..In this paper we obtain a new estimate for the value in humans by using a mathematical model of germ cell development that depends on available oocyte counts for adult women...

..Exposure-response analyses using flexible smoothers showed significant departures from linearity, particularly for PM effects...

..As a corollary, intervention strategies that decrease this rate are to be preferred to strategies that decrease the rate of early mutational events in carcinogenesis...

..In general, the gases, particularly CO, but not ozone, were much more strongly associated with mortality than was particulate matter. This association was particularly striking in Los Angeles County...

..We propose an approach to estimating human lung cancer risk associated with inhaled fibers from animal studies...

..8 per million person-years) exhibit no temporal trends over the period of the study. We estimate that approximately 94,000 cases of pleural and 15,000 cases of peritoneal mesothelioma will occur in the US over the period 2005-2050...

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..e., the traversal of normal cells by alpha particles, followed by the signaling of these cells to nearby initiated cells which then modify their proliferation kinetics...

..Females may have an inherently higher proportion of indolent lung cancers than males, or aggressive lung cancers may be brought into check by the immune system more frequently among females than males...

..There is insufficient evidence to include or exclude these processes as being potentially important to PM-associated health risk...

..Smoking a bamboo water pipe or a Chinese long-stem pipe appears to confer less risk than cigarette use, given equivalent tobacco consumption...

..The data are consistent with the hypothesis that fibers act as initiators in the rat lung. We present an estimate of the dose-dependent initiation parameter that is based on all the available data...

..Important directions in critical experiment definition are suggested, including a renewed emphasis on well-designed animal experiments over extended periods of time...

..However, the EU protocol has very low power to detect effects of short-lived fibers, such as X607, with WHL of about 10 days...

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..The age-adjusted risk among ex-smokers is somewhat higher in NHS, possibly due to differences in the age-distribution between the two cohorts...

..Experimental studies are needed to provide direct evidence for this dual role of folate in colorectal cancer and to validate and improve the model predictions...

..The linear phase of the age-specific incidence curve represents this conversion, which is the result of recessive inactivation of a gatekeeper gene, such as the APC gene in the colon and the CDKN2A gene in the pancreas...

..By contrast, interventions that decrease the rate of mutations at the adenomatous polyposis coli locus are much less effective in reducing the risk of colon cancer...

..Unfortunately for hypothesis generation, the data appear to be consistent with a number of different mechanistic interpretations of the role of radiation in carcinogenesis...

..The estimated promoting action of radon increases by a factor of up to 1.2 for the largest assumed exposure uncertainties...

..Our findings also underscore the importance of the timing (6 weeks versus 2 weeks) of the genotoxic insult in relation to the developmental stage of the liver and the importance of clonal selection during tumor promotion...

..In summary, the two-dimensional GAM performed well. The GAMs make the important prediction that female lung cancer rates in these countries will be stable or begin to decline in the future...

..We suggest a cross-validation approach to choosing a stratification model to balance the trade-off between bias and variance. We also establish a connection between the Poisson process approach and case cross-over studies...

..The importance of smoking duration on lung cancer risk in these cohorts is a direct consequence of promotion. Intervention and treatment strategies should focus on promotion as the primary etiologic mechanism in lung carcinogenesis...

..Temporal trends in the incidence of both cancers are dominated by dramatically increasing period effects...

..If the Agency justifies a particulate matter mass standard on these grounds then the debate over the form and level of the standard will, for all practical purposes, belong strictly in the Policy arena...

..The analysis of the SEER data also shows that gestational mutations could contribute to inter-individual variations in colorectal cancer risk...

..We further demonstrate the utility of our approach by computing the benefits of up to two colonoscopies on the lifetime risk of colorectal cancer...

..The main goals of these analyses are to explore the effects of various age- and time-related factors and of protraction of exposure on the risk of radiation carcinogenesis. ..

..The results of analyses will be used to help generate biologically relevant questions and hypotheses and to plan further experiments and studies, which, in turn, will lead to more refined models. ..

..We propose to explore collaboration with other investigators supported by CISNET, particularly those interested in using our model as the 'natural history' component of screening models. ..

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..A previously developed stochastic two-stage model for carcinogenesis will be extended to allow the incorporation of time- dependent covariates. The properties of this model will be investigated within the context of risk assessment...