An Investigation of the Developmental Origins of Cancer through an Analysis of Cancer Registry Data

The long-term objective of this project is to predict who is more likely to develop cancer. The main hypothesis that I tested is that the age-specific incidence of first primary cancers in the United States follows a Weibull distribution, making it possible to estimate the proportion of the population that has an innate susceptibility to developing a particular type of cancer. The results showed that approximately 12% of men and 10% of women in the U.S. are born susceptible to developing colon cancer. On the other hand, 18% of women are susceptible to developing breast cancer, while 26% of men are susceptible to developing prostate cancer. These results provided evidence supporting the notion that a small proportion of the U.S. population is born susceptible to developing colon, breast and prostate cancer, as predicted by extreme value theory.;I predicted that if an individual is born susceptible to developing a certain type of cancer, he or she is also susceptible to developing a second primary cancer in the same organ during a typical lifetime. I hypothesized that susceptible individuals have lifetime-independent odds of developing a second cancer, given a first diagnosis, significantly greater than the lifetime-independent odds of developing a first cancer. The lifetime-independent odds ratio (LIOR) provides a relative measure of the risk of developing a second primary cancer, given a first cancer diagnosis.;I confirmed the validity of applying extreme value theory to study cancer incidence in two independent ways: 1) I tested the cell senescence and frailty hypotheses by computing LIOR values from colon and breast cancer incidence data extracted from SEER, and 2) I tested the cell senescence and frailty hypotheses by formulating a stochastic model of cancer incidence to compute LIOR values based on the incidence of first and second cancers in an artificial population. In both cases, the LIOR value for second cancers was significantly greater than 1, supporting the frailty hypothesis and the predictions of extreme value theory. Based on these results, extreme value theory is applicable to the study of cancer incidence and cancer may have its origins in events that occur in utero.