Table 2.

Summary of studies about the prevalence of multiple primary colorectal carcinoma and the main molecular features of synchronous and metachronous colorectal carcinoma

Ref.	Study design	Prevalence of MPCRC (% of global)	Risk factors for MPCRC	Carcinogenetic pathways
[10]	Solitary (29) MPCRC (12) Study of MPCRC features		No differences: Age Gender Body mass index Tumour location History of CRC of MSI	CIMP-high 17.2% solitary vs 66.7% MPCRC P = 0.004
[36]	57 MPCRC Comparison of methylation status of solitary CRC vs MPCRC 57			Higher methylation for p14 MGMT in MPCRC P < 0.05 Correlations: MINT1 (r = 0.8) p16 (r = 0.8), MLH1 (r = 0.9) MGMT (r = 0.6) at the same site
[16]	4760 CRC patients Study of SCRC vs solitary CRC	58 (1.2%) SCRC: 42 (72%) sporadic 4 (7%) UC 8(14%)Lynch 1 (2%) FAP 3 (5%) SP	Older patients (P = 0.001) Right colon (P = 0.0003) Synchronous polyps (P = 0.0001) Classical adenoma 47% vs 12% SSAs 16% vs 0%	(MSI-H) 36% vs 12%; (P = 0.0005) 92% if SSA precursor
[17]	2884 patients SCRC vs solitary CRC	77 (2.7%) SCRC	21 (27%) had a family history of Lynch	54 (32%) MSI-H (> in women and elderly) congruence (MSS/MSI) Yes: 67 patients (87%) No: 10 patients (13%)
[30]	2884 CRC Study of MPCRC methylation state in SCRC vs MCRC	33 (1.1%) MCRC 77 (2.6%) SCRC	MSI-H MCRC were younger (64 vs 76 years, P =0.01)	MSI-H tumors in 12 (36%) MCRC 29 (38%) SCRCP Promoter methylation 50% MCRC 83% SCRCP P = 0.03
[35]	2,068 CRC patients SCRC vs solitary CRC	47 (2.3%) SCRC	Mean age 68.9 vs 65.5 (P =0.016) No difference: Family history of CRC BMI	MSI-high (P = 0.037). > BRAF (P = 0.0041) > CIMP-high (P = 0.013) Correlation pairs LINE-1 (r = 0.82; P = 0.0072) CpG islands (P < 0.0001)

CRC: Colorectal cancer; MCRC: Metachronous CRC; SCRC: Synchronous CRC; SSAs: Sessile serrated adenomas; UC: Ulcerative colitis; SP: Serrated polyposis; BMI: Body mass index; HR: Hazard ratio; OR: Odds ratio; MSI: Microsatellite instability; FAP: Familial adenomatous polyposis.