Table 2. Circulating concentrations of sRANKL and breast cancer risk by hormone-receptor subtype: EPIC nested case-control study.
| Quintiles |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | |||||
| Cut points (pmol/L)* | < 0.05 | 0.05-0.09 | 0.10-0.14 | 0.15-0.20 | ≥ 0.20 | ptrend† | log2 | phet‡ | phet§ |
| Whole population | |||||||||
| ER+/PR+ | |||||||||
| Cases/Controls | 167/198 | 203/183 | 176/192 | 160/157 | 214/190 | 920/920 | |||
| RR (95% CI) | ref. | 1.31 (0.96-1.80) | 1.12 (0.81-1.55) | 1.18 (0.84-1.64) | 1.36 (0.99-1.87) | 0.31 | 1.03 (0.97-1.10) | 0.05 | |
| ER+ | |||||||||
| Cases/Controls | 339/364 | 360/351 | 301/327 | 255/264 | 343/292 | 1598/1598 | |||
| RR (95% CI) | ref. | 1.11 (0.89-1.39) | 1.02 (0.80-1.29) | 1.03 (0.81-1.32) | 1.28 (1.01-1.63) | 0.20 | 1.03 (0.98-1.08) | 0.13 | |
| ER-/PR- | |||||||||
| Cases/Controls | 52/51 | 57/40 | 47/53 | 49/56 | 46/51 | 251/251 | |||
| RR (95% CI) | ref. | 1.54 (0.81-2.93) | 0.94 (0.50-1.75) | 0.81 (0.43-1.54) | 0.74 (0.39-1.38) | 0.08 | 0.89 (0.78-1.01) | ||
| ER- | |||||||||
| Cases/Controls | 84/79 | 83/63 | 73/82 | 63/85 | 75/69 | 378/378 | |||
| RR (95% CI) | ref. | 1.23 (0.74-2.03) | 0.75 (0.46-1.22) | 0.63 (0.37-1.06) | 0.87 (0.53-1.44) | 0.21 | 0.94 (0.84-1.04) | ||
| Age at diagnosis <50 years | |||||||||
| ER+/PR+ | |||||||||
| Cases/Controls | 12/12 | 27/29 | 18/21 | 24/15 | 40/44 | 121/121 | |||
| RR (95% CI) | ref. | 0.68 (0.21-2.24) | 0.56 (0.15-2.08) | 1.33 (0.37-4.81) | 0.90 (0.29-2.80) | 0.74 | 1.04 (0.81-1.34) | ||
| ER+ | |||||||||
| Cases/Controls | 16/15 | 32/34 | 21/27 | 26/18 | 48/49 | 143/143 | |||
| RR (95% CI) | ref. | 0.64 (0.22-1.81) | 0.44 (0.14-1.43) | 1.00 (0.32-3.16) | 0.78 (0.28-2.19) | 0.90 | 1.02 (0.81-1.27) | ||
| Age at diagnosis ≥50 years | |||||||||
| ER+/PR+ | |||||||||
| Cases/Controls | 155/186 | 176/154 | 158/171 | 136/142 | 174/146 | 799/799 | |||
| RR (95% CI) | ref. | 1.38 (0.99-1.92) | 1.17 (0.84-1.64) | 1.13 (0.79-1.60) | 1.44 (1.02-2.03) | 0.33 | 1.03 (0.97-1.10) | 0.05 | 0.81 |
| ER+ | |||||||||
| Cases/Controls | 323/349 | 328/317 | 280/300 | 229/246 | 295/243 | 1455/1455 | |||
| RR (95% CI) | ref. | 1.13 (0.90-1.43) | 1.05 (0.82-1.34) | 1.00 (0.78-1.29) | 1.33 (1.03-1.70) | 0.22 | 1.03 (0.98-1.08) | 0.12 | 0.90 |
| ER-/PR- | |||||||||
| Cases/Controls | 51/47 | 49/34 | 41/49 | 42/45 | 34/42 | 217/217 | |||
| RR (95% CI) | ref. | 1.51 (0.75-3.03) | 0.84 (0.43-1.64) | 0.84 (0.42-1.69) | 0.57 (0.28-1.13) | 0.06 | 0.88 (0.77-1.01) | 0.53 | |
| ER- | |||||||||
| Cases/Controls | 79/74 | 72/52 | 60/71 | 53/68 | 55/54 | 319/319 | |||
| RR (95% CI) | ref. | 1.37 (0.79-2.36) | 0.75 (0.45-1.25) | 0.70 (0.40-1.23) | 0.77 (0.44-1.33) | 0.19 | 0.93 (0.83-1.04) | 0.52 | |
*
Cutpoints reflect non-log transformed sRANKL concentrations
†
ptrend based on log2-transformed sRANKL concentrations
‡
pheterogeneity comparing ER+/PR+ to ER-/PR- and ER+ to ER- subtypes, based on RRlog2
§
pheterogeneity comparing age at diagnosis <50 to ≥50 years based on RRlog2; Conditional logistic regression models adjusted for: ages at menarche (<12, 13, 14, ≥15, missing), menopause (<44, 44-47, 48-50, 51-52, 53-54, ≥55, missing), and first full-term pregnancy (no FTP, <25, 25-30, ≥30, missing), and number of full-term pregnancies (0, 1, 2, ≥3, missing) and BMI (kg/m2, continuous).