Table 2.
Odds ratios (95% CI) of keratinocyte cancers in relation to oral contraceptive (OC) use, hormone replacement therapy (HRT) use, and reproductive factors
| SCC controls N = 746 |
SCC cases N = 570 |
BCC controls N = 550 |
BCC cases N = 633 |
Early-onset BCC controlsa N = 246 |
Early-onset BCC cases N = 362 |
||||
|---|---|---|---|---|---|---|---|---|---|
| N (%) | N (%) | OR (95% CI)b | N (%) | N (%) | OR (95% CI) | N (%) | N (%) | OR (95% CI) | |
| Oral contraception usec | |||||||||
| No | 307 (43.2) | 270 (48.6) | 1.0 (ref) | 236 (45.8) | 200 (33.6) | 1.0 (ref) | 49 (21.5) | 57 (16.6) | 1.0 (ref) |
| Yes | 404 (56.8) | 286 (51.4) | 1.4 (1.1–1.8) | 279 (54.2) | 396 (66.4) | 1.4 (1.0–1.8) | 179 (78.5) | 287 (83.4) | 1.4 (0.9–2.1) |
|
| |||||||||
| Age at last OC use | |||||||||
| Non user | 307 (45.0) | 270 (49.3) | 1.0 (ref) | 236 (48.4) | 200 (36.2) | 1.0 (ref) | 49 (24.1) | 57 (18.8) | 1.0 (ref) |
| < 29 yrs. old | 173 (25.4) | 100 (18.2) | 1.3 (0.9–1.9) | 120 (24.6) | 168 (30.4) | 1.3 (0.9–1.8) | 97 (47.8) | 144 (47.5) | 1.3 (0.8–2.0) |
| >=29 yrs. old | 202 (29.6) | 178 (32.5) | 1.4 (1.1–1.9) | 132 (27.0) | 185 (33.5) | 1.4 (1.1–2.0) | 57 (28.1) | 102 (33.7) | 1.5 (0.9–2.5) |
| Continuous | ptrend < 0.018 | ptrend < 0.019 | ptrend < 0.091 | ||||||
|
| |||||||||
| Duration of OC use | |||||||||
| Non user | 307 (43.3) | 270 (48.6) | 1.0 (ref) | 236 (46.0) | 200 (33.6) | 1.0 (ref) | 49 (21.6) | 57 (16.6) | 1.0 (ref) |
| ≤ 2 yrs. | 60 (8.5) | 35 (6.3) | 1.0 (0.7–1.7) | 41 (8.0) | 64 (10.8) | 1.6 (1.0–2.4) | 22 (9.7) | 44 (12.8) | 1.7 (0.9–3.3) |
| 3–6 yrs. | 157 (22.1) | 106 (19.1) | 1.4 (1.0–2.0) | 119 (23.2) | 149 (25.0) | 1.2 (0.8–1.6) | 87 (38.3) | 111 (32.4) | 1.1 (0.7–1.8) |
| ≥ 7 yrs. | 185 (26.1) | 144 (25.9) | 1.5 (1.1–2.0) | 117 (22.8) | 182 (30.6) | 1.5 (1.1–2.1) | 69 (30.4) | 131 (38.2) | 1.6 (1.0–2.7) |
| Continuous | ptrend < 0.030 | ptrend < 0.052 | ptrend < 0.047 | ||||||
|
| |||||||||
| Years since last OC use | |||||||||
| Non user | 307(52.6) | 270(62.5) | 1.0 (ref) | 236 (46.2) | 200(33.7) | 1.0 (ref) | 49 (21.7) | 57 (16.6) | 1.0 (ref) |
| < 25 yrs. | 213(36.5) | 77(17.8) | 1.0(0.7–1.6) | 211 (41.3) | 308(51.9) | 1.3 (1.0–1.8) | 162 (71.7) | 254 (74.1) | 1.4 (0.9–2.1) |
| ≥ 25 yrs. | 64(11.0) | 85(19.7) | 2.1(1.5–3.2) | 64 (12.5) | 85(14.3) | 1.5 (1.0–2.1) | 15 (6.6) | 32 (9.3) | 1.7 (0.8–3.7) |
| Continuous | ptrend < 0.020 | ptrend < 0.150 | ptrend < 0.895 | ||||||
|
| |||||||||
| OC formulation | |||||||||
| Non user | 307 (53.3) | 270 (59.1) | 1.0 (ref) | 236 (55.0) | 200 (39.9) | 1.0 (ref) | 49 (37.7) | 57 (27.3) | 1.0 (ref) |
| Estrogen dose ≤ 50mg | 193 (38.6) | 120 (30.8) | 1.2 (0.9–1.6) | 135 (36.4) | 166 (45.4) | 1.2 (0.8–1.6) | 91 (65.0) | 119 (67.6) | 1.1 (0.7–1.8) |
| Estrogen dose > 50mg | 211 (40.7) | 166 (38.1) | 1.5 (1.1–2.1) | 144 (37.9) | 230 (53.5) | 1.5 (1.1–2.1) | 88 (64.2) | 168 (74.7) | 1.7 (1.0–2.6) |
| Combination | 266 (46.4) | 186 (40.8) | 1.5 (1.1–2.0) | 193 (45.0) | 296 (59.7) | 1.5 (1.1–2.0) | 136 (73.5) | 230 (80.1) | 1.5 (1.0–2.3) |
| Sequential | 182 (37.2) | 141 (34.3) | 1.5 (1.1–2.1) | 124 (34.4) | 197 (49.6) | 1.5 (1.0–2.1) | 81 (62.3) | 152 (72.7) | 1.6 (1.0–2.6) |
|
| |||||||||
| Hormone replacement therapy usec, d | |||||||||
| No | 310 (58.7) | 254 (49.7) | 1.0 (ref) | 207 (60.3) | 194 (58.1) | 1.0 (ref) | |||
| Yes | 218 (41.3) | 257 (50.3) | 1.4 (1.1–1.8) | 136 (39.7) | 140 (41.9) | 1.0 (0.8–1.4) | |||
| Exclusive estrogen | 146 (32.0) | 155 (37.9) | 1.2 (0.9–1.6) | 88 (29.8) | 95 (32.9) | 1.1 (0.8–1.6) | |||
| Estrogen + progestin | 45 (12.7) | 73 (22.3) | 2.1 (1.4–3.2) | 29 (12.3) | 32 (14.2) | 1.0 (0.5–1.7) | |||
|
| |||||||||
| Age at first HRT use | |||||||||
| Non user | 310 (58.7) | 254 (49.9) | 1.0 (ref) | 207 (60.3) | 194 (58.1) | 1.0 (ref) | |||
| < 48 yrs. old | 108 (20.5) | 111 (21.8) | 1.3 (0.9–1.7) | 61 (17.8) | 60 (18.0) | 0.9 (0.6–1.4) | |||
| ≥ 48yrs.old | 110 (20.8) | 144 (28.3) | 1.5 (1.1–2.0) | 75 (21.9) | 80 (24.0) | 1.1 (0.8–1.6) | |||
| Continuous | ptrend < 0.004 | ptrend < 0.690 | |||||||
|
| |||||||||
| Duration of HRT use | |||||||||
| Never User | 310 (58.9) | 254 (50.3) | 1.0 (ref) | 207 (60.7) | 194 (58.6) | 1.0 (ref) | |||
| > 0– ≤ 5 yrs. | 83 (15.8) | 71 (14.1) | 1.1 (0.7–1.5) | 55 (16.1) | 57 (17.2) | 0.9 (0.6–1.4) | |||
| > 5 yrs. | 133 (25.3) | 180 (35.6) | 1.6 (1.2–2.1) | 79 (23.2) | 80 (24.2) | 1.1 (0.8–1.6) | |||
| Continuous | ptrend < 0.057 | ptrend < 0.566 | |||||||
|
| |||||||||
| Years since last HRT use | |||||||||
| Non User | 310 (60.5) | 254 (50.7) | 1.0 (ref) | 207 (63.1) | 194 (59.5) | 1.0 (ref) | |||
| Current User | 163 (31.8) | 190 (37.9) | 1.4 (1.1–1.8) | 89 (27.1) | 103 (31.6) | 1.2 (0.8–1.7) | |||
| Former (≥1yr) | 39 (7.6) | 57 (11.4) | 1.6 (1.0–2.5) | 32 (9.8) | 29 (8.9) | 1.0 (0.6–1.7) | |||
| Continuous | ptrend < 0.771 | ptrend < 0.696 | |||||||
|
| |||||||||
| Age at menarchee | |||||||||
| <13 yrs. old | 178 (43.3) | 120 (41.4) | 1.0 (0.7–1.4) | 104 (47.9) | 112 (43.2) | 0.8 (0.5–1.2) | 78 (51.0) | 103 (45.2) | 0.8 (0.5–1.2) |
| 13–15 yrs. old | 206 (50.1) | 155 (53.4) | 1.0 (ref) | 100 (46.1) | 130 (50.2) | 1.0 (ref) | 68 (44.4) | 112 (49.1) | 1.0 (ref) |
| >15 yrs. old | 27 (6.6) | 15 (5.2) | 0.9 (0.4–1.8) | 13 (6.0) | 17 (6.6) | 1.2 (0.5–2.6) | 7 (4.6) | 13 (5.7) | 1.2 (0.4–3.2) |
| Continuous | ptrend < 0.346 | ptrend < 0.128 | ptrend < 0.382 | ||||||
|
| |||||||||
| Menopause typef | |||||||||
| Non surgical or medication induced | 329 (46.4) | 329 (59.3) | 1.0 (ref) | 208 (40.5) | 197 (33.2) | 1.0 (ref) | 35 (15.6) | 48 (14.1) | 1.0 (ref) |
| All surgical types | 182 (25.7) | 162 (29.2) | 0.9 (0.7–1.1) | 121 (23.6) | 121 (20.4) | 1.0 (0.8–1.4) | 23 (10.3) | 40 (11.8) | 1.3 (0.7–2.5) |
| Bilateral oophorectomy | 30 (4.2) | 20 (3.6) | 0.6 (0.4–1.2) | 21 (4.1) | 21 (3.5) | 1.1 (0.6–2.1) | 3 (1.3) | 4 (1.2) | 1.0 (0.2–4.6) |
| Unilateral oophorectomy | 91 (12.8) | 87 (15.7) | 0.9 (0.7–1.3) | 57 (11.1) | 57 (9.6) | 1.1 (0.7–1.7) | 10 (4.5) | 15 (4.4) | 1.2 (0.5–2.9) |
| Hysterectomy | 56 (7.9) | 50 (9.0) | 0.9 (0.6–1.3) | 40 (7.8) | 41 (6.9) | 1.0 (0.6–1.6) | 9 (4.0) | 21 (6.2) | 1.7 (0.7–4.1) |
|
| |||||||||
| Age at natural menopause | |||||||||
| <40 yrs.old | 14 (4.4) | 11(3.4) | 0.9 (0.4–2.0) | 12 (6.0) | 5 (2.6) | 0.4 (0.1–1.2) | 0 (0) | 0 (0) | ** |
| 40–54 yrs. old | 255 (79.4) | 249 (77.6) | 1.0 (ref) | 159 (79.1) | 166 (84.7) | 1.0 (ref) | 32 (91.4) | 47(97.9) | 1.0 (ref) |
| ≥ 55 yrs. old | 52 (16.2) | 61 (19.0) | 1.1 (0.7–1.6) | 30 (14.9) | 25 (12.8) | 0.9 (0.5–1.6) | 0 (0) | 0 (0) | ** |
| Continuous | ptrend < 0.768 | ptrend < 0.595 | ** | ||||||
|
| |||||||||
| Age at surgical menopause | |||||||||
| <40 yrs.old | 16 (53.3) | 10 (50.0) | 0.8 (0.2–2.7) | 11 (52.4) | 14 (66.7) | 1.9 (0.5–7.9) | 0 (0) | 0 (0) | ** |
| 40–54 yrs. old | 13 (43.3) | 10 (50.0) | 1.0 (ref) | 10 (47.6) | 7 (33.3) | 1.0 (ref) | 3 (100.0) | 4 (100.0) | 1.0 (ref) |
| ≥ 55 yrs. old | ** | ** | 0 (0) | 0 (0) | ** | ||||
| Continuous | ptrend < 0.331 | ptrend < 0.707 | ** | ||||||
|
| |||||||||
| Parityg | |||||||||
| 0 | 71 (11.8) | 53 (10.6) | 1.0 (ref) | 49 (12.1) | 73 (14.9) | 1.0 (ref) | 34 (17.0) | 50 (16.4) | 1.0 (ref) |
| 1–2 | 291 (48.3) | 221 (44.1) | 1.0 (0.6–1.5) | 203 (50.0) | 256 (52.2) | 0.8 (0.6–1.3) | 123 (61.5) | 184 (60.3) | 1.0 (0.6–1.7) |
| 3–4 | 185 (30.7) | 177 (35.3) | 0.8 (0.5–1.3) | 115 (28.3) | 139 (28.4) | 0.9 (0.6–1.5) | 37 (18.5) | 64 (21.0) | 1.2 (0.6–2.1) |
| ≥ 5 | 55 (9.1) | 50 (10.0) | 0.7 (0.4–1.2) | 39 (9.6) | 22 (4.5) | 0.5 (0.3–1.0) | 6 (3.0) | 7 (2.3) | 0.7 (0.2–2.4) |
| Continuous | ptrend < 0.252 | ptrend < 0.199 | ptrend < 0.906 | ||||||
|
| |||||||||
| Duration of ovulationh | |||||||||
| ≤ 29 years | 19 (11.0) | 11 (7.3) | 1.0 (ref) | 10 (16.1) | 6 (10.9) | 1.0 (ref) | 4 (14.3) | 4 (10.8) | 1.0 (ref) |
| > 29–35 years | 49 (28.3) | 34 (22.5) | 1.3 (0.5–3.2) | 19 (30.6) | 16 (29.1) | 1.1 (0.3–3.8) | 11 (39.3) | 12 (32.4) | 1.1 (0.2–6.3) |
| > 35–39 years | 59 (34.1) | 63 (41.7) | 1.8 (0.7–4.1) | 21 (33.9) | 26 (47.3) | 2.2 (0.6–7.6) | 13 (46.4) | 18 (48.6) | 2.0 (0.3–12.5) |
| > 39 years | 46 (26.6) | 43 (28.5) | 1.5 (0.6–3.7) | 12 (19.4) | 7 (12.7) | 1.5 (0.3–6.8) | 0 (0.0) | 3 (8.1) | ** |
| Continuous | ptrend < 0.270 | ptrend < 0.581 | ptrend < 0.103 | ||||||
a
Early-onset BCC defined as age ≤ 50 at time of diagnosis.
b
Odds ratios and 95% confidence intervals adjusted for reference age and skin sensitivity to first solar exposure.
c
Oral contraceptive use and hormone replacement therapy questions were administered beginning on the 5th of October, 1995.
d
Hormone replacement therapies are restricted to those women who have begun menopause.
e
Age of menarche was administered beginning on the 1st of July 2000.
f
Menopause induced by medication, or non-surgical therapies were excluded from this analysis.
g
Gravidity and parity questions were administered beginning on the 1st of July 1998.
h
Endogenous estrogen exposure was calculated as the number of years between menarche and menopause in women who had reached menopause without surgery or medication therapy.