BACKGROUND: Common low-penetrance genetic variants have been consistently associated with colorectal cancer risk. AIM: To determine if these genetic variants are associated also with adenoma susceptibility and may improve selection of patients with increased risk for advanced adenomas and/or multiplicity (≥ 3 adenomas). METHODS: We selected 1,326 patients with increased risk for advanced adenomas and/or multiplicity and 1,252 controls with normal colonoscopy from population-based colorectal cancer screening programs. We conducted a case-control association study analyzing 30 colorectal cancer susceptibility variants in order to investigate the contribution of these variants to the development of subsequent advanced neoplasia and/or multiplicity. RESULTS: We found that 14 of the analyzed genetic variants showed a statistically significant association with advanced adenomas and/or multiplicity: the probability of developing these lesions increased with the number of risk alleles reaching a 2.3-fold risk increment in individuals with ≥ 17 risk alleles. CONCLUSIONS: Nearly half of the genetic variants associated with colorectal cancer risk are also related to advanced adenoma and/or multiplicity predisposition. Assessing the number of risk alleles in individuals within colorectal cancer screening programs may help to identify better a subgroup with increased risk for advanced neoplasia and/or multiplicity in the general population.

This work was supported by grants from: Instituto de Salud Carlos III-FEDER (RD09/0076/00036), the Xarxa de Bancs de tumors sponsored by Pla Director d'Oncologia de Catalunya (XBTC), Fondo de Investigación Sanitaria/FEDER (PI10/00918, PI11/00219, PI14/00173, PI14/00441), Ministerio de Economía y Competitividad (SAF2010-19273), Asociación Española contra el Cáncer (Fundación Científica GCB13131592CAST), and COST Action BM1206 (SCB). SCB is supported by a contract from the Fondo de Investigación Sanitaria (CP 03-0070) and Agència de Gestió d'Ajuts i de Recerca (Generalitat de Catalunya, 2014SGR255, 2014SGR135). CIBERehd is funded by the Instituto de Salud Carlos III.