Abstract 1446: Genetic risk factors for the development of multiple primary cancers

Introduction: Individuals with one cancer are at greater risk of new primary cancers than the general population. While several hereditary cancer syndromes are known, genetic risk factors for multiple primary cancers in an individual are not well understood. Identification of susceptibility variants to multiple primary tumors could enhance screening for subsequent cancers among those at highest risk. Methods: We conducted a pan-cancer genome-wide association study (GWAS) of multiple primary cancers among participants from 2 prospective cohorts: Kaiser Permanente and the UK Biobank. The primary GWAS within cohorts used logistic regression to estimate associations for diagnosis with ≥2 invasive or in situ primary cancers other than non-melanoma skin (N=11,773, 8,928 invasive only) compared to cancer-free controls (N=420,101). Case-case analyses were conducted to distinguish associations with multiple cancers from single-cancer (N=90,576) susceptibility signals. Regression models were adjusted for age, sex, first 10 genetic ancestry principal components, and array. Cohort-specific GWAS results were meta-analyzed. We highlight genome-wide significant (p