TABLE 2.
Summary of germline testing results in the cohorts examined. The total number of individuals in each cohort and the number of individuals who are positive with one or more pathogenic/likely pathogenic variants is shown (top panel). Cases designated as medullary thyroid cancer were excluded from this analysis. The number of pathogenic/likely pathogenic variants identified in each gene is shown next to the number of times that gene was included in a panel test (bottom panel). Genes with the highest frequency (freq.) of pathogenic variants are shown (shaded). Refer to Table S3
| Thyroid cancer cohort | Thyroid cancer only | Thyroid and breast cancer | Breast cancer only | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n | 3134 | 904 | 1521 | 78,141 | |||||||||
| Positive a | 291 (9.3) | 68 (7.5) | 147 (9.7) | 6530 (8.4) | |||||||||
| Moderate | |||||||||||||
| CHEK2 I157T | 22 (0.7) | 5 (0.6) | 10 (0.7) | 325 (0.4) | |||||||||
| APC I1307K | 11 (0.4) | 4 (0.4) | 3 (0.2) | 95 (0.1) | |||||||||
| Negative | 2096 (66.9) | 603 (66.7) | 1062 (69.8) | 54,977 (70.4) | |||||||||
| Inconclusive | 676 (21.6) | 208 (23.0) | 287 (18.9) | 15,416 (19.7) | |||||||||
| MUTYH carrier | 38 (1.2) | 16 (1.8) | 12 (0.8) | 798 (1.0) | |||||||||
| Gene name | No. positive (n) | No. tested (n) | Freq. | No. positive (n) | No. tested (n) | Freq. | No. positive (n) | No. tested (n) | Freq. | No. positive (n) | No. tested (n) | Freq. | p‐value |
| DICER1 | 1 | 14 | 7.14% | 1 | 8 | 12.50% | 0 | 2 | 0.00% | 0 | 119 | 0.00% | 0.08 c |
| CHEK2 | 93 | 2327 | 4.00% | 20 | 690 | 2.90% | 53 | 1091 | 4.86% | 1379 | 61344 | 2.25% | <0.001 b |
| CHEK2 I157T | 22 | 2327 | 0.95% | 5 | 690 | 0.72% | 10 | 1091 | 0.92% | 317 | 61344 | 0.52% | 0.14 c |
| Other CHEK2 | 71 | 2327 | 3.05% | 15 | 690 | 2.17% | 43 | 1091 | 3.94% | 1062 | 61344 | 1.73% | <0.001 b |
| ATM | 32 | 2188 | 1.46% | 8 | 635 | 1.26% | 18 | 1080 | 1.67% | 667 | 61349 | 1.09% | 0.17 c |
| APC | 18 | 1477 | 1.22% | 9 | 500 | 1.80% | 2 | 529 | 0.38% | 102 | 18363 | 0.56% | 0.01 c |
| APC I1307K | 9 | 1477 | 0.61% | 4 | 500 | 0.80% | 2 | 529 | 0.38% | 91 | 18363 | 0.50% | 0.52 c |
| Other APC | 9 | 1477 | 0.61% | 5 | 500 | 1.00% | 0 | 529 | 0.00% | 11 | 18363 | 0.06% | <0.001 c |
| BRCA2 | 33 | 2780 | 1.19% | 6 | 816 | 0.74% | 22 | 1442 | 1.53% | 1303 | 76195 | 1.71% | 0.08 c |
| BRCA1 | 19 | 2780 | 0.68% | 4 | 816 | 0.49% | 8 | 1442 | 0.55% | 1226 | 76195 | 1.61% | <0.001 c |
| SDHB | 4 | 585 | 0.68% | 0 | 182 | 0.00% | 1 | 158 | 0.63% | 3 | 3462 | 0.09% | 0.17 c |
p values of < 0.05 are shown in bold.
The following pathogenic/likely pathogenic variants are not included in the “positive results” in this study: alterations designated as "moderate risk" (CHEK2 I157T, and APC I1307K), and MUTYH monoallelic carriers.
p‐value from chi‐squared test for the difference in proportions across all mutually exclusive groups (TCa vs. Tca+BCa vs. BCa).
p‐value from Fisher’s exact test for the difference in proportions across all mutually exclusive groups (TCa vs. Tca+BCa vs. BCa).