Table 4.
Associations of CYP19A1 and ESR1 genotypes with analysis endpoints
| Univariate model | Multivariableb model | Multivariablec model | ||||||
|---|---|---|---|---|---|---|---|---|
| Gene: SNP | Comparisons | Numbera (events) | Odds ratio (95 % CI) | P value | Odds ratio (95 % CI) | P value | Odds ratio (95 % CI) | P value |
| Hot flashes/sweating | ||||||||
| CYP19A1: rs4646 | Dose effectd | 1965 (848) | 1.05 (0.91,1.21) | 0.50 | 1.04 (0.90,1.20) | 0.63 | 1.08 (0.93,1.25) | 0.30 |
| CYP19A1: rs10046 | T/T vs. C/T,C/C (ref) | 446 (172) vs. 1519 (676) | 0.78 (0.63,0.97) | 0.03 | 0.82 (0.66,1.02) | 0.08 | 0.83 (0.66,1.04) | 0.10 |
| ESR1:rs2077647 | Dose effect | 1965 (848) | 0.95 (0.84,1.08) | 0.47 | 0.96 (0.84,1.09) | 0.51 | 0.97 (0.85,1.11) | 0.69 |
| ESR1:rs2234693 (PvuII) | Dose effect | 1965 (848) | 0.92 (0.80,1.04) | 0.18 | 0.92 (0.80,1.04) | 0.19 | 0.94 (0.82,1.07) | 0.36 |
| ESR1:rs9340799 (XbaI) | Dose effect | 1965 (848) | 0.94 (0.82,1.08) | 0.38 | 0.94 (0.82,1.07) | 0.34 | 0.98 (0.85,1.12) | 0.73 |
| Musculoskeletal symptoms | ||||||||
| CYP19A1: rs4646 | Dose effectd | 1966 (516) | 1.01 (0.86,1.18) | 0.90 | 1.05 (0.89,1.24) | 0.55 | 1.11 (0.93,1.31) | 0.25 |
| CYP19A1: rs10046 | T/T vs. C/T,C/C (ref) | 446 (110) vs. 1520 (406) | 0.90 (0.70,1.15) | 0.39 | 0.86 (0.66,1.10) | 0.23 | 0.84 (0.65,1.09) | 0.18 |
| ESR1:rs2077647 | Dose effect | 1966 (516) | 1.08 (0.94,1.25) | 0.28 | 1.12 (0.96,1.30) | 0.15 | 1.11 (0.95,1.29) | 0.20 |
| ESR1:rs2234693 (PvuII) | Dose effect | 1966 (516) | 1.03 (0.90,1.19) | 0.65 | 1.07 (0.92,1.25) | 0.37 | 1.06 (0.91,1.24) | 0.47 |
| ESR1:rs9340799 (XbaI) | Dose effect | 1966 (516) | 1.06 (0.91,1.23) | 0.44 | 1.10 (0.94,1.29) | 0.22 | 1.11 (0.94,1.30) | 0.22 |
Analysis endpoints were early-onset (within 6 months) grade ≥2 hot flashes/sweating or (within 12 months) grade ≥2 musculoskeletal symptoms. aPatients without any adverse event data, excluded from analyses (2 without hot flashes/sweating and one without musculoskeletal symptoms). bMultivariable logistic regression model adjusted for characteristics: age, menstruation status, BMI, adjuvant chemotherapy use, treatment assignment, and presence of hot flashes/sweating at baseline or of musculoskeletal symptoms at baseline (according to endpoint). cMultivariable model also adjusted for relevant concomitant medications prior to or continuing at baseline, and use during relevant time period for the endpoint. dDose effect: comparisons of variant (Var) allele groups: 0 (Var) vs. 1 (Var) vs. 2 (Var). SNP single nucleotide polymorphism