Data from Interaction between Continuous Pack-Years Smoked and Polygenic Risk Score on Lung Cancer Risk: Prospective Results from the Framingham Heart Study

• DOI: 10.1158/1055-9965.c.7162281.v1
• Publication Date: 2024-04-03T07:22:14Z
• Authors: Meredith S. Duncan; Hector Diaz-Zabala; James Jaworski; Hilary A. Tindle; Robert A. Greevy; Loren Lipworth; Rayjean J. Hung; Matthew S. Freiberg; Melinda C. Aldrich
• Keywords: Polygenic risk score; Framingham Heart Study

<div>AbstractBackground:<p>Lung cancer risk attributable to smoking is dose dependent, yet few studies examining a polygenic score (PRS) by interaction have included comprehensive lifetime pack-years smoked.</p>Methods:<p>We analyzed data from participants of European ancestry in the Framingham Heart Study Original (<i>n</i> = 454) and Offspring 2,470) cohorts enrolled 1954 1971, respectively, followed through 2018. We built PRS for lung using participant genotyping genome-wide association study summary statistics recent OncoArray Consortium. used Cox proportional hazards regression models assess between smoked genetic adjusting ancestry, age, sex, education.</p>Results:<p>We observed significant submultiplicative on (<i>P</i> 0.09). Thus, relative associated with each additional 10 decreased increasing (HR 1.56 at one SD below mean PRS, HR 1.48 1.40 above PRS). Similarly, per increase was highest among those who had never 1.55) heavier 1.32 30 pack-years).</p>Conclusions:<p>These results suggest presence genetics risk, consistent findings. Both were significantly risk.</p>Impact:<p>These underscore contributions highlight negative impact continued regardless risk.</p></div>