Introduction
Hereditary nonpolyposis colorectal cancer (HNPCC)
Clinical diagnosis
Criteria Items colorectal cancer patients | Amsterdam criteria (including I and II) ≥3 (including extracolonic tumours) | Japanese criteria A ≥3 | Chinese criteria ≥2 | Japanese criteria B ≥2 | Bethesda guidelines (2004) ≥1 |
---|---|---|---|---|---|
first-degree relatives | at least 2 pairs | at least 2 pairs | at least 1 pair | at least 1 pair | no request |
generations affected | at least 2 successive generations | no request | no request | no request | no request |
exclude FAP | yes | no request | no request | no request | no request |
with any of these: | at least 1 should be diagnosed before age 50 | no request | at least 1 should be diagnosed before age 50 | at least 1 should be diagnosed before age 50 | CRC diagnosed before age 50 |
multiple colorectal tumors (including adenomas) | multiple colorectal cancers | Multiple colorectal tumors | |||
extracolorectal cancer | extracolorectal cancer | HNPCC-associated tumours | |||
right colon involvement | MSI-H pathologic associated features in a colorectal cancer diagnosed before age 60 | ||||
- one with colorectal cancer - one or more first - or second-degree relatives with HNPCC-related tumour - one of the cancers being diagnosed before age 50 | |||||
- one with colorectal cancer - two or more first - or second-degree relatives with HNPCC-related tumour |
Genetics
Family | Criteria | mutation in: | mutation type | reference | |
---|---|---|---|---|---|
MLH1 | MSH2 | ||||
C4 | Amsterdam | E18 c.2081 int T | E15 c.2469 int C | frameshift | [16] |
c.2471 int G | frameshift | ||||
c. 2578 int T | frameshift | ||||
C11 | Amsterdam | E13 c.2091 T>A | nonsense | [16] | |
C13 | Amsterdam | E11 c.1760int T | frameshift | [16] | |
c.1688 A>C | missense | ||||
H2 | Amsterdam | E13 c.2038 C>T | nonsense | [17] | |
H4 | Amsterdam | E2 c.199 A>G | missense | [18] | |
H9 | Amsterdam | E11 c.305 del 24bp | small deletion | [17] | |
H11 | Amsterdam | E1 c.14 A>C | missense | [17] | |
H27 | Amsterdam | E3 c.617 int A | frameshift | [17] | |
N8 | Amsterdam | E8 c.655 A>G | missense | [19] | |
N11 | Amsterdam | E3 c.265 G>T | nonsense | [19] | |
N14 | Amsterdam | E6 c.545+3 A>G | splice point | [19] | |
N23 | Amsterdam | E3 c.610 G>T | nonsense | [19] | |
N25 | Amsterdam | E8 c.677 G>A | missense | [19] | |
HW7 | Amsterdam | E14 c.2228 C>A | nonsense | [20] | |
HW5 | Amsterdam | E14 c.1588-1590 del | small deletion | [20] | |
C1 | Japan | E11 c.934 int A | frameshift | [21] | |
C6 | Japan | E1 c.21 G>C | missense | [22] | |
C8 | Japan | E12 c.1198 C>G | missense | [21] | |
c.1261 C>G | missense | ||||
c.1364 int C | frameshift | ||||
c.1372 int C | frameshift | ||||
N18 | Japan | E9 c.790+1 G>A | splice point | [19] | |
N26 | Japan | E14 c.2211-2 A>C | splice point | [19] | |
HW6 | Japan | E15 c.1731+1 A>G | missense | [20] | |
H12 | China | E15 c.2516 G>A | missense | [18] | |
H20 | China | E19 c.2250 G>C | nonsense | [18] | |
H5 | * | E3 c.425 G>C | nonsense | [23] | |
H6 | * | E15 c.1731 G>A | splice point | [23] | |
H17 | * | E15 c.1731 G>A | splice point | [23] | |
H45 | * | E16 c.1846 del AAG | small deletion | [23] | |
H47 | * | E12 c.1151 T>A | missense | [23] | |
H52 | * | E2 c.194 G>A | missense | [23] | |
H56 | * | E16 c.2792 A>C | missense | [23] | |
H62 | * | E14 c.1588 del TTC | small deletion | [23] | |
H64 | * | E15 c.1731+1 G>A | splice point | [23] | |
H65 | * | E14 c.2228 C>A | nonsense | [23] | |
H67 | * | E14 c.1559-2 G>A | splice point | [23] | |
H68 | * | E2 c.137 G>T | missense | [23] | |
E11 c.914 int 24 | frameshift | [23] |
Clinical manifestations
Amsterdam criteria cases (%) | Japanese criteria cases (%) | Chinese/Korean criteria cases (%) | Sporadic CRC cases (%) | |
---|---|---|---|---|
1. Gender
| ||||
male | 166 (55) | 53 (48) | 14 (33) | 437 (47) |
female | 136 (45) | 57 (52) | 28 (67) | 50 (53) |
2. Location
| ||||
right colon | 85 (40) | 33 (26) | 144 (10) | |
other colon | 155 (73) | 65 (52) | 26 (62) | 540 (39) |
rectum | 57 (27) | 60 (48) | 16 (38) | 853 (61) |
3. Duke's stage
| ||||
A&B | 67 (63) | 42 (46) | 34 (81) | 387 (49) |
C&D | 40 (37) | 49 (54) | 8 (19) | 400 (51) |
4. Differentiation
| ||||
low grade | 17 (40) | 24 (39) | 5 (13) | 108 (14) |
high grade | 25 (50) | 38 (61) | 34 (87) | 664 (86) |
5. Multiple malignancy
| ||||
total | 25 (9) | 19 (15) | 6 (14) | 25 (3) |
synchronous | 5 (2) | 11 (9) | ||
metachronous | 20 (7) | 8 (6) | ||
not multiple | 260 (91) | 110 (85) | 36 (86) | 867 (97) |
6. Adenomas
| ||||
with adenomas | 13 (18) | 6 (21) | 98 (18) | |
without adenomas | 58 (82) | 23 (79) | 450 (82) |