Table 2.
Analyses of Variables Associated With Presence of a Germline Mismatch Repair Gene Mutation (Bivariate Analysis)a
| Variable | Evaluable Probands, No.b |
MMR Gene Carriers Fulfilling the Condition, No./Total No.c |
OR (95% CI)d | % (95% CI) | |||
|---|---|---|---|---|---|---|---|
| Sensitivity | Specificity | PPV | NPV | ||||
| Proximal CRCe | 1644 | 130/208 | 2.5 (1.7–3.7) | 62.3 (55.6–69.3) | 51.4 (48.7–53.9) | 15.6 (13.1–18.2) | 90.4 (88.3–92.5) |
| Mucinous CRC | 1492 | 52/201 | 1.7 (1.2–2.4) | 25.9 (19.5–32.1) | 84.0 (82.0–86.0) | 20.2 (15.0–25.2) | 87.9 (86.0–89.7) |
| Poorly differentiated CRC | 745 | 24/104 | 1.3 (0.8–2.1) | 23.1 (14.5–31.6) | 81.1 (78.0–84.2) | 16.6 (10.1–22.9) | 86.7 (83.8–89.4) |
| Crohn-like lymphocytic reaction | 300 | 27/55 | 2.0 (1.1–3.7) | 49.1 (34.9–63.2) | 67.8 (61.7–73.8) | 25.5 (16.7–34.2) | 85.6 (80.3–90.7) |
| Tumor infiltrating lymphocytes | 367 | 44/64 | 3.2 (1.7–5.9) | 68.8 (56.6–80.8) | 61.7 (56.0–67.3) | 27.5 (20.2–34.7) | 90.3 (86.0–94.6) |
| Synchronous or metachronous CRC |
2160 | 50/244 | 5.0 (3.3–7.8) | 20.7 (15.4–26.0) | 94.3 (93.2–95.3) | 31.4 (23.9–38.9) | 90.5 (89.1–91.7) |
| Metachronous Lynch syndrome– related tumorf |
2650 | 53/311 | 5.1 (3.4–7.7) | 17.0 (12.7–21.3) | 95.7 (94.8–96.5) | 34.6 (26.7–42.5) | 89.6 (88.4–90.8) |
| CRC excluded | 2650 | 21/311 | 4.7 (2.6–8.4) | 6.7 (3.8–9.7) | 97.6 (97.0–98.2) | 27.6 (16.9–38.3) | 88.7 (87.4–89.9) |
| Diagnosed ≤50 y | 2649 | 36/310 | 6.2 (3.7–10.4) | 11.6 (7.8–15.3) | 98.4 (97.8–98.9) | 48.6 (36.5–60.7) | 89.3 (88.1–90.5) |
| CRC excluded (diagnosed ≤50 y) |
2650 | 12/311 | 4.2 (1.9–9.2) | 3.8 (1.5–6.1) | 99.1 (98.7–99.5) | 37.5 (19.1–55.8) | 88.5 (87.5–89.8) |
| FDR with CRC ≥1 |
2644 | 131/308 | 3.0 (2.3–4.1) | 42.5 (37.0–48.4) | 81.9 (80.3–83.5) | 23.7 (20.1–27.4) | 91.5 (90.3–92.7) |
| ≥2 | 2644 | 56/306 | 5.0 (3.3–7.6) | 18.3 (13.8–22.8) | 96.0 (95.1–96.8) | 37.3 (29.2–45.4) | 90.0 (88.7–91.1) |
| FDR with CRC diagnosed ≤50 y ≥1 |
2610 | 79/289 | 8.0 (5.5–11.8) | 27.3 (22.2–32.9) | 96.3 (95.4–97.0) | 47.6 (40.0–55.7) | 91.5 (90.2–92.5) |
| ≥2 | 2633 | 22/297 | 11.9 (5.4–26.0) | 7.4 (4.2–10.5) | 99.5 (99.1–99.8) | 64.7 (47.1–82.2) | 89.4 (88.2–90.6) |
| FDR with Lynch syndrome– related tumorf ≥1 |
2640 | 154/303 | 2.8 (2.1–3.7) | 50.8 (45.0–56.6) | 74.0 (72.1–75.7) | 20.2 (17.2–23.1) | 92.1 (90.8–93.3) |
| ≥2 | 2648 | 88/310 | 4.5 (3.1–6.4) | 28.4 (23.1–33.5) | 93.2 (92.1–94.2) | 35.5 (29.3–41.6) | 90.8 (89.5–91.9) |
| FDR with Lynch syndrome– related tumor diagnosed ≥50yf ≥1 |
2589 | 95/281 | 5.7 (4.1–8.0) | 33.8 (28.1–39.5) | 92.9 (91.8–94.0) | 36.8 (30.7–42.9) | 92.0 (90.9–93.1) |
| ≥2 | 2619 | 32/283 | 12.4 (6.6–23.0) | 11.3 (7.9–15.8) | 99.1 (98.7–99.5) | 61.5 (49.1–76.7) | 90.3 (89.0–91.3) |
| CRC diagnosed ≤70 y (Jerusalem recommendations) |
2112 | 226/240 | 4.0 (2.2–7.1) | 94.2 (90.4–97.0) | 26.3 (24.4–28.3) | 13.4 (11.7–15.0) | 97.0 (94.7–98.3) |
| Fulfillment of Amsterdam criteria I |
2627 | 41/291 | 9.6 (5.7–16.2) | 13.7 (9.5–17.7) | 98.6 (98.1–99.1) | 55.6 (43.3–67.7) | 90.2 (88.9–91.2) |
| II | 2650 | 85/312 | 11.4 (7.3–17.7) | 27.2 (22.1–32.3) | 97.9 (97.3–98.5) | 63.4 (54.9–71.9) | 91.0 (89.7–92.0) |
| Fulfillment of ≥1 criterion of revised Bethesda guidelines |
2128 | 214/243 | 7.3 (4.6–11.0) | 88.1 (83.7–92.3) | 54.4 (52.1–56.6) | 19.9 (17.4–22.3) | 97.3 (96.2–98.2) |
Abbreviations: CRC, colorectal cancer; FDR, first-degree relative; MMR, mismatch repair; NPV, negative predictive value; OR, odds ratio; PPV, positive predictive value.
This analysis was limited to patients with information on the germline mutational status of MMR genes and without considering the result of tumor MMR testing.
Probands in whom the corresponding variable could be assessed.
MMR gene carriers fulfilling the condition with respect to those MMR gene carriers in whom the corresponding variable could be evaluated.
Adjusted by age, sex, and participating center.
With respect to the splenic flexure.
Lynch syndrome–related tumors: colorectal, endometrial, ovarian, gastric, hepatobiliary, small bowel, urinary tract, pancreatic, and brain cancer.