Electronic Thesis and Dissertation Repository


Master of Science


Epidemiology and Biostatistics


Dr. Yun-Hee Choi


In genetic epidemiology, families harboring certain genetic mutations are predisposed to successive cancers in their lifetime. This thesis aims to provide reliable estimates of relative risk and age-dependent cumulative risks (penetrance) associated with the mutated gene for successive cancers. We develop a statistical framework for modeling sequential event times arising from family data. A shared frailty model is employed to incorporate the dependence between the two event times. Because families are ascertained through non-random sampling, an ascertainment-corrected retrospective likelihood approach is proposed to account for the non-ignorable sampling design. Simulation studies demonstrate that our proposed method provides unbiased and reliable estimates of disease risks associated with a mutated gene. The frailty approach is also compared to an independent model that ignores the dependence between the events. Finally, we illustrate our approach using 12 Lynch syndrome families and provide penetrance estimates for developing first and second colorectal cancer.

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