“…Despite this knowledge, much of the genetic predisposition to CRC is still unexplained. In the last years, by using genome‐wide approaches such as whole‐genome and whole‐exome sequencing, or copy number variation (CNV) analysis, multiple candidate genes for CRC predisposition have been proposed, including RPS20 (MIM# 603682), IL12RB1 (MIM# 601604), LIMK2 (MIM# 601988), POLE2 (MIM# 602670), MRE11 (MIM# 600814), POT1 (MIM# 606478), FAN1 (MIM# 613534), WIF1 (MIM# 605186), HNRNPA0 (MIM# 609409), SEMA4A (MIM# 607292), FOCAD (MIM# 614606), PTPN12 (MIM# 600079), LRP6 (MIM# 603507), POLQ (MIM# 604419), BLM (MIM# 604610), MCM9 (MIM# 610098), and the epigenetic inactivation of PTPRJ (MIM# 600925), among others (Chubb, Broderick, Dobbins, Frampton et al, 2016; de Voer et al, 2015; de Voer et al, 2016; Goldberg et al, 2015; Kinnersley et al, 2016; Nieminen et al, 2014; Raskin et al, 2017; Schulz et al, 2014; Segui et al, 2015; Sill, Schulz, Steinke‐Lange, & Boland, 2016; Spier et al, 2015; Valle, 2017; Venkatachalam et al, 2010; Venkatachalam et al, 2011; Wei et al, 2015; Weren et al, 2015). The reported supporting evidence varies considerably among candidate genes: while some studies provide evidence of co‐segregation, somatic second hits, functional effects and/or higher mutational frequency in cases versus controls, other reports are inconclusive.…”