Table II.
ORs and 95% CIs for biliary tract cancers and stones in relation to ESR variants
| Genotype | Controls | Gallbladder cancera |
Bile duct cancerb |
Ampulla of Vater cancerb |
Biliary stonesc |
||||
| n | n | OR (95% CI)d | n | OR (95% CI)d | n | OR (95% CI)d | n | OR (95% CI)d | |
| ESR1 | |||||||||
| IVS1-397C>T (rs2234693) | |||||||||
| CC | 314 | 94 | 1.0 | 48 | 1.0 | 18 | 1.0 | 341 | 1.0 |
| CT | 356 | 100 | 0.9 (0.7–1.3) | 54 | 1.0 (0.7–1.9) | 24 | 1.2 (0.6–2.3) | 401 | 1.1 (0.9–1.4) |
| TT | 108 | 41 | 1.2 (0.8–1.9) | 21 | 1.3 (0.8–2.4) | 5 | — | 138 | 1.3 (0.9–1.7) |
| P-trend | 0.57 | 0.39 | 0.98 | 0.16 | |||||
| CT/TT | 464 | 141 | 1.0 (0.7–1.3) | 75 | 1.1 (0.8–1.6) | 29 | 1.12 (0.61–2.05) | 539 | 1.1 (0.9–1.4) |
| IVS5-34->T (rs3841686) | |||||||||
| — | 357 | 95 | 1.0 | 67 | 1.0 | 17 | 1.0 | 399 | 1.0 |
| T | 317 | 115 | 1.4 (1.0–1.9) | 43 | 0.7 (0.5–1.1) | 22 | 1.4 (0.7–2.7) | 377 | 1.1 (0.9–1.3) |
| TT | 105 | 24 | 0.8 (0.5–1.3) | 14 | 0.7 (0.4–1.3) | 8 | 1.7 (0.7–4.0) | 105 | 0.9 (0.6–1.2) |
| P-trend | 0.90 | 0.12 | 0.20 | 0.64 | |||||
| T/TT | 422 | 139 | 1.2 (0.9–1.6) | 57 | 0.7 (0.5–1.0) | 30 | 1.5 (0.8–2.7) | 482 | 1.0 (0.8–1.3) |
| Ex4-122G>C (rs1801132) (P325P) | |||||||||
| CC | 219 | 65 | 1.0 | 23 | 1.0 | 7 | 1.0 | 249 | 1.0 |
| CG | 377 | 116 | 1.0 (0.7–1.5) | 69 | 1.8 (1.1–2.9) | 23 | 1.9 (0.8–4.4) | 435 | 1.0 (0.8–1.3) |
| GG | 181 | 53 | 0.9 (0.6–1.4) | 32 | 1.7 (1.0–3.1) | 16 | 2.8 (1.1–6.9) | 201 | 1.0 (0.7–1.3) |
| P-trend | 0.70 | 0.07 | — | 0.03 | — | 0.94 | |||
| CG + GG | 558 | 169 | 1.0 (0.7–1.4) | 101 | 1.7 (1.1–2.8) | 39 | 2.1 (0.9–4.9) | 636 | 1.0 (0.8–1.3) |
| Ex8+229A>G (rs2228480) | |||||||||
| AA | 467 | 136 | 1.0 | 85 | 1.0 | 27 | 1.0 | 528 | 1.0 |
| AG | 271 | 90 | 1.2 (0.9–1.6) | 33 | 0.7 (0.4–1.0) | 15 | 1.0 (0.5–1.8) | 301 | 1.0 (0.8–1.3) |
| GG | 43 | 9 | 0.7 (0.3–1.5) | 7 | 0.8 (0.3–1.8) | 5 | — | 51 | 1.0 (0.6–1.6) |
| P-trend | 0.94 | 0.09 | 0.54 | 0.88 | |||||
| AG/GG | 314 | 99 | 1.1(0.8–1.5) | 40 | 0.7 (0.4–1.0) | 20 | 1.1 (0.6–1.9) | 352 | 1.0 (0.8–1.3) |
| p-globale | 1.0 | 0.07 | 0.1 | 0.9 | |||||
| P-globalf | 0.8 | 0.02 | 0.3 | 0.8 | |||||
| ESR2 | |||||||||
| Ex6+32G>A (rs1256049) (V328V) | |||||||||
| AA | 332 | 101 | 1.0 | 54 | 1.0 | 19 | 1.0 | 381 | 1.0 |
| AG | 357 | 105 | 1.0 (0.7–1.3) | 56 | 1.0 (0.6–1.4) | 25 | 1.2 (0.7–2.3) | 380 | 0.9 (0.7–1.1) |
| GG | 90 | 27 | 1.0 (0.6-1.6) | 14 | 1.0 (0.5–1.8) | 3 | — | 120 | 1.2 (0.9–1.7) |
| P-trend | 0.87 | 0.83 | 0.77 | 0.70 | |||||
| AG/GG | 447 | 132 | 1.0 (0.7-1.3) | 70 | 1.0 (0.6–1.4) | 28 | 1.1 (0.6–2.0) | 500 | 1.0 (0.8–1.2) |
| 38 bp 3′ of STP (rs4986938) | |||||||||
| AA | 589 | 174 | 1.0 | 91 | 1.0 | 32 | 1.0 | 669 | 1.0 |
| AG | 170 | 56 | 1.2 (0.8–1.6) | 24 | 0.9 (0.6–1.5) | 14 | 1.5 (0.8–2.9) | 187 | 1.0 (0.8–1.3) |
| GG | 13 | 4 | — | 7 | 3.3 (1.3–8.7) | 0 | — | 16 | 1.2 (0.5–2.9) |
| P-trend | 0.76 | 0.25 | 0.77 | 0.72 | |||||
| AG/GG | 183 | 60 | 1.1 (0.8–1.6) | 31 | 1.1 (0.7–1.7) | 14 | 1.4 (0.7–2.7) | 203 | 1.0 (0.8–1.3) |
| P-globale | 0.9 | 0.5 | 0.4 | 0.4 | |||||
| P-globalf | 0.8 | 0.9 | 0.5 | 0.9 | |||||
| P-FDR for all six SNPs | 0.9 | 0.2 | 0.9 | 0.9 | |||||
Bold values are statistically significant at P < 0.05.
FDR, false discovery rate.
a
Gallbladder cancer cases compared with controls without cholecystectomy (n = 737).
b
Bile duct and ampulla of Vater cancer cases compared with all controls (n = 786).
c
Biliary stone cases compared with controls without biliary stones (n = 592).
d
ORs (95% CI) were adjusted for age and sex. The ORs (95% CI) persisted after adjusting for gallstones.
e
Gene-level global p-values by summarizing the likelihood ratio tests for the additive genetic effects.
f
Gene-level global p-values by summarizing the likelihood ratio tests for the dominant genetic effects.