Table 3.
Comparison of studies on pathogenic variants in CRC patients
| Matthew et al. (7) | Pearlman et al. (11) | Saud et al. (12) | Stoffel et al. (5) | Our study | |
|---|---|---|---|---|---|
| n = 1058 (%) | n = 450 (%) | n = 680 (%) | n = 430 (%) | n = 88 (%) | |
| Age of diagnosis (mean ± SD), y | 55.7 ± 12.6 | 42.5 | 68.8 ± 10.3 | 40.0 | 41.4 ± 0.8 |
| Study setting | Gastrointestinal cancer institute | General oncology clinics | General oncology clinics | Cancer genetics clinics | General oncology clinic |
| Genetic studies | Next-generation sequencing | Next-generation sequencing | Next-generation sequencing | Next-generation sequencing | Next-generation sequencing digitalMLPA |
| Functional studies | None | Tumor LOH | Tumor LOH | None | Tumor LOH; homologous recombination assay (RAD51) |
| CRCs in first-degree relatives | 138 (13.0) | 33 (45.8) | 164 (25.0) | 111 (25.8) | 13 (18.6) |
| Breast cancers in first-degree relatives | 138 (13.0) | 8 (11.1) | 85 (19.0) | NA | 4 (5.7) |
| Ovarian cancers in first-degree relatives | 23 (2.2) | 2 (2.8) | 19 (4.3) | NA | 1 (1.4) |
| Any cancers in first-degree relatives | 870 (82.2) | 53 (11.8) | 395 (59.0) | NA | 33 (36.3) |
| MMR-deficient tumors/MSI-H | 83 (14.5); 486 missing data | 48 (10.7); no missing data | 92 (16.0); 113 missing data | 41 (20.1); 226 missing data | 0 (0.0); 19 missing data |
| CRC predisposition genes tested | APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, TP53 | APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, TP53 | APC, BMPR1A, CHEK2, MLH1, MSH2, MSH6, MUTYH, PMS2, POLD1, POLE, PTEN, SMAD4, STK11, TP53 | APC, AXIN2, BMPR1A, BRAF, CDH1, CHEK2, EPCAM, KRAS, MLH1, MSH2, MSH6, MUTYH, PMS2, POLD1, POLE, PTEN, SMAD4, STK11, TP53 | APC, AXIN2, BMPR1A, BRAF, CDH1, CHEK2, EPCAM, FLCN, GREM1, MLN1, MSH2, MSH6, MUTYH, PMS2, POLD1, POLE, PTEN, SMAD4, STK11, TP53 |
| DNA repair genes tested | ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK4, CDKN2A, CHEK2, NBN, PALB2, RAD51C, RAD51D | ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK4, CDKN2A, CHEK2, NBN, PALB2, RAD51C, RAD51D | ATM, ATR, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, DDB2, ERCC2, ERCC3, ERCC4, ERCC5, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, GEN1, MRE11, NBN, NTHL1, PALB2, PCNA, POLH, RAD51, RAD51C, RAD51D, RAD54L, RECQL4, SLX4, UBE2T, WRN, XPA, XPC, XRCC3 | AKT1, ALK, ARID1A, ATR, AURKA, BAP1, BARD1, BRCA1, BRCA2, BRIP1, CASP8, CDKN2A, CTNNB1, ERBB3, FAM123B, FAT1, FBXW7, FGFR3, GALNT12, GREM1, HNF1A, HOXB12, HRAS, IGF1, IGF2, IGF2R, MEN1, MET, MSH3, MYC, NBN, NOTCH1, PALB2, PIK3CA, PTCH1, PTPN11, RAD51, SDHB, SMAD2, SMAD3, SMAD7, SOX9, SYNE1, TERT, TET2, TGFRB2, VHL | ATM, ATR, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CDKN2A, CDK4, DDB2, ERCC2, ERCC3, ERCC4, ERCC5, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, GEN1, MITF, MRE11A, NBN, NTHL1, PALB2, RAD50, RAD51, RAD51C, RAD51D, RAD54L, RECQL4, RET, RFWD3, SLX4, UBE2T, WRN, XPA, XPC, XRCC2 |
| DNA used | Germline DNA | Germline DNA and tumor DNA | Germline DNA | Germline DNA | Germline DNA and tumor DNA |
| Pathogenic variants in CRC predisposition genes | MLH1 (n=13), MSH2 (n=7), MSH6 (n=6), PMS2 (n=7), MUTYH biallelic (n=3), APC (n=19), MUTYH monoallelic (n=18), CHEK2 (n=2) | MLH1 (n=13), MSH2 (n=16), MSH6 (n=2), PMS2 (n=5), MUTYH biallelic (n=4), APC (n=10), MUTYH monoallelic (n=7), SMAD4 (n=1) | MSH2 (n=1), MSH6 (n=1), PMS2 (n=2), APC (n=10), MUTYH monoallelic (n=11), CHEK2 (n=4), TP53 (n=2) | MLH1 (n=24), MSH2 (n=25), MSH6 (n=5), PMS2 (n=2), MUTYH biallelic (n=6), APC (n=8), MUTYH monoallelic (n=1), SMAD4 (n=2), CHEK2 (n=1) | APC (n=4), MUTYH monoallelic (n=2) |
| Pathogenic variants in DNA repair genes | ATM (n=10), BARD1 (n=1), BRCA1 (n=3), BRCA2 (n=8), BRIP1 (n=3), CDKN2A (n=1), NBN (n=2), PALB2 (n=2), TP53 (n=1) | ATM (n=4), BRCA1 (n=2), BRCA2 (n=4), CDKN2A (n=1) and PALB2 (n=2) | ATM (n=5), BAP1 (n=1), BARD1 (n=1), BLM (n=3), BRCA1 (n=1), BRCA2 (n=4), BRIP1 (n=2), ERCC2 (n=2), ERCC3 (n=1), ERCC4 (n=1), FANCC (n=1), FANCE (n=1), FANCL (n=1), GEN1 (n=2), MRE11 (n=2), PALB2 (n=3), POLH (n=1), RECQL4 (n=2), SLX4 (n=1), XPA (n=1), XRCC3 (n=1) | BRCA1 (n=1), TP53 (n=1) | ATM (n=1), BRCA2 (n=1), NTHL1 (n=1), PALB2 (n=1), WRN (n=2) |
| Features of patients with pathogenic CRC predisposition gene variants* | Younger age† | Younger age | Younger age | Right-sided colon involvement† | Younger age† |
| Right-sided colon involvement† | Right-sided colon involvement | Family history of breast cancers† | MSI tumors† | Earlier stage of diagnosis† | |
| Earlier stage of diagnosis† | Earlier stage of diagnosis | MSI tumors | Family history of CRCs† | ||
| MSI tumors† | MSI tumors | Earlier stage of diagnosis† | |||
| Personal and family history of multiple CRCs† | Personal and family history of multiple CRCs* | ||||
| Features of patients with pathogenic DNA repair gene variants* | None | None | None | None | None |
*
Compared to noncarriers of germline pathogenic variants. CRC= colorectal cancer; digitalMLPA = digital multiplex ligation-dependent probe amplification; MMR= mismatch repair; MSI-H = microsatellite instability-high.
†
Statistical significance (P < .05) was observed.