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The manuscript suggests a possible role of MLH1 c.655A>G (Ile219Val, rs1799977), MSH2 c.1168C>T (Leu390Phe, rs5028341), APC 4479 G>A (p.Thr1493Thr, rs41115), and APC - G3949C (p.Glu1317Gln, rs1801166) polymorphisms in the susceptibility to early onset of CRC. Additionally, multiple genetic changes in MLH1 and APC genes can predispose the early development of colon or rectum cancer in patients with family history of CRC. But it remains to be further investigated with additional samples. Deletion at codon 1205 (c.3613delA) of APC gene seems to be differentially associated with early-onset cases depending on having a polyposis and family history of CRC.