Table. Cohort Characteristics and Cancer Associations Stratified by Wild-type vs Monoallelic Pathogenic Variants.
| Characteristic | No. (%) | CHEK2 monoallelic PV vs WT | ||
|---|---|---|---|---|
| WT | CHEK2 monoallelic PVa | OR (95% CI) | P value | |
| Sexb | ||||
| Female | 30 429 (92.1) | 1995 (92.0) | 0.99 (0.85-1.17) | .93 |
| Male | 2605 (7.9) | 172 (7.9) | ||
| Age, median (IQR), y | ||||
| At genetic testing | 53 (44-63) | 53 (43-62) | NA | .005 |
| At first breast cancer | 50 (43-59) | 47 (41-56) | NA | <.001 |
| At first cancer | 49 (42-58) | 47 (40-56) | NA | <.001 |
| Race and ethnicity, ancestry | ||||
| African American/Black | 1815 (5.5) | 37 (1.7) | 0.26 (0.18-0.36) | <.001 |
| Ashkenazi Jewish | 2247 (6.8) | 92 (4.2) | 0.53 (0.42-0.65) | <.001 |
| Asian | 1071 (3.2) | 20 (0.9) | 0.24 (0.15-0.37) | <.001 |
| Hispanic | 1582 (4.8) | 66 (3.0) | 0.54 (0.41-0.69) | <.001 |
| White | 21 907 (66.3) | 1707 (78.7) | 0.72 (0.62-0.82) | <.001 |
| Other | 4409 (13.4) | 246 (11.4) | 1.43 (1.29-1.58) | <.001 |
| Any cancer | ||||
| Yes | 23 065 (69.8) | 1664 (76.8) | NA | NA |
| No | 9969 (30.2) | 504 (23.3) | NA | NA |
| Primary cancers, No. | ||||
| 0 | 9969 (30.2) | 504 (23.3) | NA | <.001 |
| 1 | 18 498 (56.0) | 1348 (62.2) | NA | |
| >1 | 4567 (13.8) | 316 (14.6) | NA | |
| Breast cancer | ||||
| Yes | 16 029 (52.7) | 1339 (67.1) | 1.83 (1.66-2.02) | <.001 |
| No | 13 584 (44.6) | 620 (31.1) | ||
| Bilateral breast cancer | ||||
| Yes | 2228 (7.3) | 273 (13.7) | 1.99 (1.74-2.28) | <.001 |
| No | 27 345 (89.9) | 1683 (84.4) | ||
| First breast cancer ER/PR positivec | ||||
| Yes | 8355 (78.0) | 837 (92.8) | 3.64 (2.81-4.78) | <.001 |
| No | 2362 (22.0) | 65 (7.2) | ||
| First breast cancer ERBB2 positive | ||||
| Yes | 1492 (19.0) | 168 (25.9) | 1.49 (1.23-1.79) | <.001 |
| No | 6362 (81.0) | 482 (74.2) | ||
| Colorectal cancer | ||||
| Yes | 2575 (7.8) | 109 (5.0) | 0.62 (0.51-0.76) | <.001 |
| No | 29 550 (89.5) | 2015 (92.9) | ||
| Kidney cancer | ||||
| Yes | 214 (0.7) | 36 (1.7) | 2.57 (1.75-3.68) | <.001 |
| No | 31 896 (96.6) | 2088 (96.3) | ||
| Melanoma | ||||
| Yes | 1259 (3.8) | 60 (2.8) | 0.71 (0.54-0.93) | .01d |
| No | 30 854 (93.4) | 2064 (95.2) | ||
| Pancreatic cancer | ||||
| Yes | 597 (1.8) | 20 (0.9) | 0.5 (0.3-0.78) | <.001 |
| No | 31 517 (95.4) | 2104 (97.1) | ||
| Thyroid cancer | ||||
| Yes | 696 (2.1) | 74 (3.4) | 1.63 (1.26-2.08) | <.001 |
| No | 31 416 (95.1) | 2050 (94.6) | ||
Abbreviations: ER, estrogen receptor; ERBB2, formerly HER2 (human epidermal growth factor receptor 2); NA, not applicable; PR, progesterone receptor; PV, pathogenic or likely pathogenic variant; WT, wild type.
a
Excluding the lower risk CHEK2 variants: p.I157T, p.S428F, and p.T476M.
b
Sex was not available for 1 participant.
c
ER/PR positive breast cancer included tumors that were estrogen receptor positive and/or progesterone receptor positive.
d
After Bonferroni correction, this P value was not significant.