A Comparison of Statistical Approaches for Genetic Anticipation with Application to Pancreatic Cancer

Genetic anticipation for a particular disease can involve an earlier age at onset (or, diagnosis), greater severity, and/or a higher number of affected individuals in successive generations within a family. The variable of interest in our study of genetic anticipation was age at diagnosis of pancreatic cancer for different generations, with and without adjustment for time under observation. We compared nonparametric and semiparametric statistical tests for paired data. This comparison was illustrated on an example of familial pancreatic cancer where study subjects were taken from the Pancreatic Cancer Collaborative Registry (PCCR). The nonparametric test performed on our example better than the two semiparametric tests, and was more efficient in detecting risk differences at earlier ages. After adjusting for follow up time, all methods detected genetic anticipation