Table 2.
Associations between MLH1 methylation and selected variables in CIMP-positive1 colorectal cancer
| Methylated2 Weighted N3 (%) |
Not Methylated2 Weighted N (%) |
Univariate P- value (Chi Square) |
OR (95% CI)4 for MLH1 methylation |
P-value for OR |
|
|---|---|---|---|---|---|
| Age | |||||
| <50 | 8 (1.9) | 45 (11.6) | 1.0 | ||
| 51–69 | 191 (47.4) | 215 (55.9) | <0.0001 | 5.85 (2.29, 15.0) | 0.0002 |
| ≥ 70 | 204 (50.7) | 125 (32.5) | 5.97 (2.32, 15.4) | 0.0002 | |
| Sex | |||||
| Male | 98 (24.3) | 229 (58.4) | <0.0001 | 1.0 | |
| Female | 305 (75.7) | 160 (41.6) | 2.76 (1.85, 4.11) | <0.0001 | |
| Tumor Site5 | |||||
| Proximal | 369 (91.7) | 267 (69.5) | 3.20 (1.35, 7.60) | 0.0084 | |
| Distal | 22 (5.4) | 61 (15.9) | <0.0001 | 0.85 (0.29, 2.53) | 0.7713 |
| Rectal | 12 (2.9) | 56 (14.6) | 1.0 | ||
| MSI status6 | |||||
| MSS | 5 (1.17) | 275 (71.7) | |||
| MSI-L | 1 (0.25) | 80 (20.7) | <0.0001 | Infinite6 | - |
| MSI-H | 395 (98.6) | 29 (7.51) | <0.0001 | ||
| BRAF mutation | |||||
| Present7 | 327 (86.2) | 162 (42.3) | 2.50 (1.53, 4.08) | ||
| Absent | 52 (13.8) | 221 (57.7) | <0.0001 | 1.0 | 0.0002 |
| KRAS mutation | |||||
| Present8 | 7 (2.1) | 131 (39.5) | 0.10 (0.04, 0.24) | ||
| Absent | 319 (97.9) | 201 (60.5) | <0.0001 | 1.0 | <0.0001 |
| Family History9 | |||||
| No | 311 (78.0) | 321 (84.0) | 1.0 | ||
| Yes | 88 (22.0) | 61 (16.0) | 0.0266 | 1.04 (0.64, 1.69) | 0.8859 |
Defined as a % methylated reference – see text (PMR) was ≥10 for at least 3 of 5 genes: CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1.
MLH1 was defined as methylated if the PMR was ≥ 10.
As defined in the text the sampling weights are the inverse of the sampling fraction which corrected for the oversampling of case probands by age, race and family history. N’s are rounded to the nearest whole number.
The odds ratio (OR) was estimated using unconditional logistic regression for odds of MLH1 methylation controlling for all other variables in the table except MSI status which effects could not be estimated due to small cell-specific numbers in the methylated-MSS group resulting in an estimate of infinity.
Tumors were labeled as ascending colon if located in the cecum through the splenic flexure. Tumors were labeled as distal colon if located in the descending colon through the sigmoid colon and included tumors ‘overlapping the colon and rectum.’ Tumors were labeled as rectal if located in the rectum or rectosigmoid junction.
MSI status was determined using 10 microsatellites as described in the text.
Presence of the BRAF V600E mutation.
Presence of either a codon 12 or codon 13 KRAS mutation.
Defined as a Self-reported history of CRC in at least one 1st degree relative.