Table 1:
Prevalence of LS and other cancer pre-disposition genes by multi-gene panel testing
| Reference | Study population | Germline pathogenic mutation carriers n (% of total cohort) |
Prevalence of LS n (% of total cohort) |
Prevalence of non-LS mutations n (% of total cohort) |
VUS rate n (%) |
|---|---|---|---|---|---|
| Colon cancer patients (unselected by age, personal/family history, MSI/MMR-D status) | |||||
| Yurgelun (2017)21 | 1058 patients with CRC, clinic-based cohort | 105 (9.9%) | 33 (3.1%) MLH1: 13 (1.2%) MSH2: 7 (0.7%) MSH6: 6 (0.6%) PMS2: 7 (0.7%) |
Overall: 74 (7%)* APC: 5 (0.5%); biallelic MUTYH: 3 (0.3%) BRCA1: 3 (0.3%); BRCA2: 8 (0.8); PALB2: 2 (0.2%); CKDN2A: 1 (0.1%); TP53: 1 (0.1%) |
330 (31.2%) |
| Early-onset colon cancer patients (age < 50 years) | |||||
| Pearlman (2017)44 | 450 early-onset CRC patients, population-based cohort | 72 (16%) | Overall: 37 (8.2%) MLH1: 13 (2.9%) MSH2: 17 (3.8%) MSH6: 2 (0.4%) PMS2: 5 (1.1%) |
Overall: 34 (7.6%)* APC: 6 (1.3%); biallelic MUTYH: 4 (0.9%), SMAD4: 1 (0.7%) ATM: 4 (0.9%); BRCA1: 2 (0.4%); BRCA2: 4 (0.9%); CDKN2A: 1 (2%); CHEK2: 1 (0.7%); PALB2: 2 (0.4%) |
145 (32.2%) |
| Stoffel (2018)45 | 430 early-onset CRC patients, clinic-based cohort | 79 (18.4%) | 56 (13%) MLH1: 24 (5.6%) MSH2: 25 (5.8%) MSH6: 5 (1.2%) PMS2: 2 (0.5%) |
Overall: 23 (5.3%) APC: 10 (2.3%); MUTYH: 8 (1.9%) BRCA1: 1 (0.2%); CHEK2: 1 (0.2%); SMAD4: 2 (0.5%); TP53: 1 (0.2%), |
21 (4.9%) |
| High risk patients (personal history of LS-associated cancer and/or colorectal polyps) | |||||
| Yurgelun (2015)42 | 1260 patients referred for LS testing, commercial testing laboratory cohort | 182 (14.4%) | 114(9.0%) MLH1: 31 (27%) MSH2: 40 (35%) MSH6: 26 (23%) PMS2: 14 (12%) EPCAM: 3 (3%) |
Overall: 71 (5.6%)* APC: 5 (0.4%); biallelic MUTYH: 3 (0.2%); STK11: 1 (0.1%) BRCA1: 6 (0.5%), BRCA2: 9 (0.7%) |
479 (38%) |
| Endometrial cancer patients (unselected by age, personal/family history, MSI/MMR status) | |||||
| Ring (2016)43 | 381 EC patients, clinic-based cohort | 35 (9%) | 22 (6%) MLH1: 3 (0.8%) MSH2: 5 (1.3%) MSH6: 6 (1.6%) PMS2: 6 (1.6%) EPCAM-MSH2: 2 (0.5%) |
Overall: 13 (3%) APC: 1 (0.3%); ATM: 1 (0.3%); BARD1: 1 (0.3%); BRCA1: 1 (0.3%); BRCA2: 1 (0.3%); BRIP1: 1 (0.3%); CHEK2: 4 (1%); NBN: 1 (0.3%); PTEN: 1 (0.3%); RAD51C: 1 (0.3%) |
Not reported |
Includes some moderate and lower penetrant genes not listed in this table
APC, adenomatous polyposis coli; ATM, ataxia-telangiesctasia mutated; BARD1, BRCA1 associated RING domain 1; BRCA1, breast cancer DNA repair-associated gene 1; BRCA2, breast cancer DNA repair-associated gene 2; BRIP1, BRCA1 interacting protein C-terminal helicase 1; CDKN2A, cyclin-dependent kinase Inhibitor 2A; CHEK2, checkpoint kinase 2; CRC, colorectal cancer; EC, endometrial cancer; EPCAM, epithelial cellular adhesion molecule; LS, Lynch syndrome; MLH1, MutL homolog 1; MSH2, MutS homolog 2; MSH6, MutS Homolog 6; PALB2, partner and localizer of BRCA2; PMS2, PMS1 homolog 2; PTEN, phosphatase and tensin homolog; MUTYH, mutY DNA glycosylase; NBN, nibrin; PTEN, phosphatase and tensin homolog; RAD51C, RAD51 paralog C; SMAD4, SMAD family member 4; STK11, serine/threonine kinase 11; VUS, variant of undetermined significance