Significance analysis and relative hazards for single traits and trait-scores affecting the risks of bone marrow failure (BMF), solid tumor (ST), and acute myeloid leukemia (AML)
. | . | Adverse event* . | . | . | . | . | . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | Frequency, % . | BMF . | . | ST . | . | AML . | . | |||||
. | . | RH†(95% Cl) . | Raw P‡(adjusted P)§ . | RH . | Raw P . | RH . | Raw P . | |||||
| Binary traits | ||||||||||||
| Absent or abnormal radial ray (RAD) | 12.5 | 5.5 (2.8-11) | 3.5 × 10−5 (3.5 × 10−4) | 0.0 | .669 | 0.0 | .469 | |||||
| Developmental delay | 27.1 | 2.0 (1.1-3.6) | 0.021 (0.060) | 3.6 | .095 | 3.0 | .163 | |||||
| Cardiopulmonary abnormality | 18.8 | 2.3 (1.2-4.6) | 0.022 (0.060) | 2.7 | .265 | 0.0 | .225 | |||||
| Abnormal kidney (horseshoe, pelvic, ectopic, absent) | 40.3 | 1.8 (1.1-3.1) | 0.024 (0.063) | 1.2 | .757 | 1.8 | .386 | |||||
| Abnormal hearing or deafness | 41.7 | 1.8 (1.0-3.0) | 0.037 (0.063) | 0.4 | .181 | 0.3 | .155 | |||||
| Abnormal head, including microcephaly | 39.6 | 1.8 (1.0-3.0) | 0.038 (0.063) | 2.4 | .129 | 1.2 | .787 | |||||
| Stature below 10th percentile | 72.9 | 1.5 | 0.178 | 0.7 | .535 | 1.7 | .475 | |||||
| Abnormal lower limbs, including dislocated hips | 6.9 | 1.5 | 0.480 | 3.1 | .209 | 0.0 | .341 | |||||
| Absent or abnormal thumbs | 56.3 | 0.9 | 0.585 | 1.4 | .576 | 1.3 | .672 | |||||
| Other skeletal abnormalities | 16.0 | 1.1 | 0.880 | 0.8 | .765 | 0.6 | .563 | |||||
| Trait scores∥ | ||||||||||||
| Simplified score | —** | 1.07 per trait¶ | 0.344 | 1.13 | .342 | 1.35 | .119 | |||||
| CABS10 | —** | 1.18 (1.1-1.3) per trait | 0.004 | 1.07 | .557 | 1.03 | .866 | |||||
| CABS | —** | 1.37 (1.2-1.6) per trait | 0.001 | 1.15 | .446 | 1.05 | .844 | |||||
| Adjusted effects# | ||||||||||||
| CABS 10 adjusted for RAD | —** | 1.08 | 0.52 | —** | —** | —** | —** | |||||
| CABS adjusted for RAD | —** | 1.23 (1.0-1.5) per trait | 0.047 | —** | —** | —** | —** | |||||
| RAD adjusted for CABS | —** | 3.63 (1.7-7.9) | 0.002 | —** | —** | —** | —** | |||||
. | . | Adverse event* . | . | . | . | . | . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | Frequency, % . | BMF . | . | ST . | . | AML . | . | |||||
. | . | RH†(95% Cl) . | Raw P‡(adjusted P)§ . | RH . | Raw P . | RH . | Raw P . | |||||
| Binary traits | ||||||||||||
| Absent or abnormal radial ray (RAD) | 12.5 | 5.5 (2.8-11) | 3.5 × 10−5 (3.5 × 10−4) | 0.0 | .669 | 0.0 | .469 | |||||
| Developmental delay | 27.1 | 2.0 (1.1-3.6) | 0.021 (0.060) | 3.6 | .095 | 3.0 | .163 | |||||
| Cardiopulmonary abnormality | 18.8 | 2.3 (1.2-4.6) | 0.022 (0.060) | 2.7 | .265 | 0.0 | .225 | |||||
| Abnormal kidney (horseshoe, pelvic, ectopic, absent) | 40.3 | 1.8 (1.1-3.1) | 0.024 (0.063) | 1.2 | .757 | 1.8 | .386 | |||||
| Abnormal hearing or deafness | 41.7 | 1.8 (1.0-3.0) | 0.037 (0.063) | 0.4 | .181 | 0.3 | .155 | |||||
| Abnormal head, including microcephaly | 39.6 | 1.8 (1.0-3.0) | 0.038 (0.063) | 2.4 | .129 | 1.2 | .787 | |||||
| Stature below 10th percentile | 72.9 | 1.5 | 0.178 | 0.7 | .535 | 1.7 | .475 | |||||
| Abnormal lower limbs, including dislocated hips | 6.9 | 1.5 | 0.480 | 3.1 | .209 | 0.0 | .341 | |||||
| Absent or abnormal thumbs | 56.3 | 0.9 | 0.585 | 1.4 | .576 | 1.3 | .672 | |||||
| Other skeletal abnormalities | 16.0 | 1.1 | 0.880 | 0.8 | .765 | 0.6 | .563 | |||||
| Trait scores∥ | ||||||||||||
| Simplified score | —** | 1.07 per trait¶ | 0.344 | 1.13 | .342 | 1.35 | .119 | |||||
| CABS10 | —** | 1.18 (1.1-1.3) per trait | 0.004 | 1.07 | .557 | 1.03 | .866 | |||||
| CABS | —** | 1.37 (1.2-1.6) per trait | 0.001 | 1.15 | .446 | 1.05 | .844 | |||||
| Adjusted effects# | ||||||||||||
| CABS 10 adjusted for RAD | —** | 1.08 | 0.52 | —** | —** | —** | —** | |||||
| CABS adjusted for RAD | —** | 1.23 (1.0-1.5) per trait | 0.047 | —** | —** | —** | —** | |||||
| RAD adjusted for CABS | —** | 3.63 (1.7-7.9) | 0.002 | —** | —** | —** | —** | |||||
A total of 144 patients contributed 1931.5 person-years of follow-up, 57 BMF events, 13 STs, and 9 AMLs.
Relative hazards estimated using the Cox proportional hazards model.
P from likelihood ratio test in the Cox proportional hazards model unadjusted for multiple comparisons.
Adjusted P values from the Benjamini-Hochberg FDR procedure; these are shown whenever the raw P values are less than or equal to .05.
Simplified score predicts diepoxybutane sensitivity. CABS 10, indicates number of abnormalities present in the complete set of 10 binary traits shown in the table. CABS, number of abnormalities in the set developmental delay, cardiopulmonary abnormality, abnormal kidney, abnormal hearing or deafness, abnormal head, and stature below the 10th percentile.
RH gives relative hazard per trait; RH for k traits versus none equals RHk, k = 1,..., 5.
Adjusted effects from multivariate Cox proportional hazards model. RH for CABS adjusted for RAD equals 1.23, 1.52, 1.87, 2.30, and 2.83 given presence of k = 1,..., 5 traits, respectively.
The frequencies of continuous scores and traits are not applicable. Adjusted effects for ST and AML were not computed because the component binary traits were not significant.