Prospective population-based cohort study of age-dependent interplay of modifiable risk factors and genetic risk in pancreatic cancer

A prospective population-based cohort study using data from participants in the UK Biobank investigated whether the potential association of modifiable risk factors (smoking, excessive alcohol intake, unhealthy diet, physical inactivity, overweight, diabetes, and pancreatitis) for pancreatic cancer (PC) varies across genetic risk profiles and age. The study included 290 645 participants, enrolled from 2006 to 2010 and followed up for a median 11.7 years (IQR 10.9-12.9). During follow-up, 1187 particpants (0.41%) developed incident PC. The joint associations of modifiable risk factors and genetic risk with PC decreased with increasing age. Potential reductions in incidence associated with having a favorable profile of modifiable risk factors were higher among individuals at high versus low genetic risk, and this pattern was more evident in participants younger than 60 years than in older age groups. The authors conclude that these findings support prioritizing early-life prevention efforts for PC, especially among individuals at high genetic risk.