Molecular genetics of early-onset colorectal cancer

Table 1 Differences in early-onset colorectal cancer and later-onset colorectal cancer DNA mutations

Gene	Prevalence in EOCRC vs LOCRC1	Role in cancer
APC	Decreased[33,34,44,45]	Blocks β-catenin, tumor suppressor
CTNNB1	Increased[33,34]	β-catenin, potentiates Wnt signaling, proliferation, and stemness
RNF43	Increased[43]/NS[33]	E3 ligase, negative regulator of Wnt signaling
BRCA2	Increased[54]	Double stranded DNA repair, tumor suppressor
PHLPP1	Increased[54]	Promotes apoptosis, inhibits AKT
TOPORS	Increased[54]	Regulates TP53 stability, likely tumor suppressor
ATR	Increased[54]	PI3/PI4 kinase, activates checkpoint proteins
MYCBP2	Increased[54]	MYC binding protein, activates MYC
FBXW7	Increased[44,54]	Ubiquitin ligase component, ubiquitinates MYC
POLE	Increased[44,54]	DNA polymerase E subunit, proofreading and DNA repair
BRAF	Decreased[34,38,57]/increased[43]	Proto-oncogene, activates MAPK signaling
TP53	Decreased[38,52]	Cell cycle inhibitor, tumor suppressor
NOMO1	Increased[53,126]	Inhibits nodal signaling. Deletion increases CRC cell migration
MYC	Increased[50,51]/NS[43,47]	Proto-oncogenic transcription factor, promotes proliferation and stemness
DNMT3B	Decreased[43]	De-novo DNA methyltransferase
MET	Decreased[43]	Proto-oncogene, promotes cell growth and survival
PTEN	Increased[57]	Tumor suppressor, negatively regulates AKT signaling
KRAS	Decreased[99,120]	Proto-oncogene, activates oncogenic signaling pathways

¹Increase or decrease in the prevalence of genomic mutations or copy number variations in early-onset colorectal cancer compared with later-onset colorectal cancer tumors.

CRC: Colorectal cancer; NS: Not significant.

Table 2 Differentially expressed transcripts in early-onset colorectal cancer

Gene(s)	Description
MYC	Proto-oncogenic transcription factor, increased in EOCRC tumors vs normal samples[50,69]
ASCL2	Transcription factor that promotes intestinal stem cells, increased expression in younger CRC[69]
ALDH1A1	Protein involved in cancer cell stemness, expressed higher in EOCRC tumors[88]
PEG10	Promotes proliferation and invasion, increased in EOCRC tumor vs normal and EOCRC vs LOCRC[70]
miR-143, miR-125b	miRNAs, under-expressed in EOCRC tumor vs normal[76]
miR-106a	miRNA, overexpressed in EOCRC tumor vs normal[76]
hsa-miR-4304, hsa-miR-513a-5p, hsa-miR-628-3p, hsa-miR-194-3p, hsa-miR-193a-5p, hsa-miR-210, and hsa-miR-4453	miRNAs uniquely overexpressed in EOCRC compared with LOCRC and normal tissues[75]
SAA1, C7, CFD	Immune genes differentially expressed in EOCRC vs LOCRC tumors[73]
NRF2	Protein involved in oxidative stress and inflammation, expressed higher in EOCRC vs LOCRC[74]

CRC: Colorectal cancer; EOCRC: Early-onset colorectal cancer; LOCRC: Later-onset colorectal cancer; miRNA: microRNAs.

Table 3 Early-onset colorectal cancer biomarkers

Name	Type	Description
mSEPT9	Methylation, DNA	Blood-based biomarker used in Epi proColon® or both EOCRC and LOCRC[112]
miR-193a-5p, miR-210, miR-513a-5p, miR-628-3p	miRNAs	miRNA in serum, panel works for both EOCRC and LOCRC[75]
Sat2, LINE-1, Alu	Methylation, DNA	DNA repetitive elements with increased methylation in EOCRC in white blood cells[62]
miR-31-5p, DMD	miRNA, mRNA	Transcripts uniquely overexpressed in sporadic EOCRC tumor vs normal and not in LOCRC. miR-3105p targets DMD and it's downregulated in EOCRC[116]
MYC	mRNA	Transcription factor with increased tumor expression in EOCRCs may subset patients into distinct groups[50,69]

EOCRC: Early-onset colorectal cancer; LOCRC: Later-onset colorectal cancer; miRNA: microRNAs.