Previous studies of anticipation in familial pancreatic cancer have been small and subject to ascertainment bias.
Dr Greenhalf and colleagues determined evidence for anticipation in a large number of European families.
A total of 1223 individuals at risk from 106 families, including 264 affected individuals, were investigated.
Generation G3 was defined as the latest generation that included any individual aged over 39 years.
|Pancreatic cancer death occurred at 70 years for a preceding generation vs 49 years for the latest generation|
The investigative team then defined preceding generations as G2 and G1.
The investigators found that with 80 affected child-parent pairs, the children died a median of 10 years earlier.
The median age of death from pancreatic cancer was 70, and 64 years for the preceding generations G1, and G2, respectively.For the latest generation, G3, the team found that the median age of death from pancreatic cancer was 49 years.
The team noted that these indications of anticipation could be the result of bias.
Truncation of Kaplan-Meier analysis was used to a 60 year period to correct for follow up time bias.
A matched test statistic indicated significant anticipation.
To minimise bias further, the team developed an iterative analysis to predict cancer numbers.
No single risk category could be applied that accurately predicted cancer cases in every generation.
Using 3 risk categories, the investigators estimated incidence without significant error.
In addition, the investigators observed that anticipation was independent of smoking.
Dr Greenhalf's team concludes, “This study provides the first strong evidence for anticipation in familial pancreatic cancer and must be considered in genetic counselling and the commencement of secondary screening for pancreatic cancer.”