Genetic Variants Associated with Colorectal Adenoma Susceptibility

PLoS One. 2016 Apr 14;11(4):e0153084. doi: 10.1371/journal.pone.0153084. eCollection 2016.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Aged
  • Alleles
  • Case-Control Studies
  • Colorectal Neoplasms / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide*
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Risk Factors

Grants and funding

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 Universitaris i de Recerca (Generalitat de Catalunya, 2014SGR255, 2014SGR135). CIBERehd is funded by the Instituto de Salud Carlos III.