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Chunk #6 — The Limits of Epidemiology — Temporal issues and their implication for mechanisms

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Moderate alcohol consumption and breast cancer in women: from epidemiology to mechanisms and interventions.
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Based on studies of known chemical carcinogens in humans, it has been estimated that it takes at least 20 years from exposure to a carcinogen to a clinical cancer diagnosis (Bielas and Loeb, 2005; Pierce et al., 1992). This surprisingly long time frame has recently received additional support from whole genome analyses of human cancers. Deep sequencing analysis of pancreatic cancers, as well as mathematical modeling (Yachida et al., 2010), estimated that the time between a tumor-initiating mutation and the non-metastatic founder cell is ≈12 years. After that, additional years are necessary for that individual cancer cell to proliferate into a tumor large enough to be detected clinically. Based on measurements of the size of breast cancers in vivo, tumor volume doubling times have been estimated to be 100–200 days (Spratt et al., 1996; von Fournier et al., 1980). Assuming continuous exponential growth, with these doubling times, it would take roughly 8–16 years for a single cancer cell to grow into a clinically detectable tumor (Spratt et al., 1995; von Fournier et al., 1980). It should be also noted that