Table 3.
Associations between SNPs in genes involved in the estrogen pathway and mammographic density
| Mean mammographic density | |||||||
|---|---|---|---|---|---|---|---|
| Percent density (%) (95% CI)a | Absolute density (cm2)b (95% CI) | ||||||
| Gene name | SNP reference IDc | Genotype | N (%)d | Crude | Adjustede | Crude | Adjustede |
| ERα | rs2077647 | TT | 189 (25.96) | 42.5 (39.0-46.0) | 42.5 (39.7-45.4) | 47.7 (43.6-51.9) | 47.6 (43.8-51.7) |
| TC | 357 (49.04) | 42.5 (40.0-45.1) | 42.5 (40.5-44.6) | 47.8 (44.8-50.8) | 47.1 (44.3-50.0) | ||
| CC | 182 (25.00) | 42.6 (39.0-46.1) | 43.3 (40.4-46.3) | 45.5 (41.5-49.7) | 44.8 (40.9-48.8) | ||
| Ptrendf | 0.98 | 0.69 | 0.48 | 0.31 | |||
| rs2234693 | AA | 211 (28.71) | 41.6 (38.3-44.8) | 42.3 (39.5-45.0) | 48.0 (44.1-52.0) | 48.3 (44.6-52.2) | |
| AG | 350 (47.62) | 42.6 (40.1-45.2) | 42.1 (40.0-44.2) | 47.6 (44.7-50.7) | 46.7 (43.9-49.7) | ||
| GG | 174 (23.67) | 42.7 (39.1-46.3) | 43.7 (40.7-46.7) | 45.2 (41.1-49.4) | 44.3 (40.4-48.4) | ||
| Ptrend | 0.63 | 0.50 | 0.35 | 0.16 | |||
| rs9340799 | AA | 301 (40.95) | 42.1 (39.3-44.8) | 42.7 (40.5-45.0) | 49.1 (45.8-52.5) | 49.4 (46.2-52.6) | |
| AG | 327 (44.49) | 42.2 (39.6-44.9) | 41.8 (39.6-43.9) | 45.8 (42.8-49.0) | 44.6 (41.7-47.5) | ||
| GG | 107 (14.56) | 43.9 (39.3-48.5) | 44.9 (41.1-48.7) | 46.6 (41.4-52.2) | 46.2 (41.2-51.6) | ||
| Ptrend | 0.58 | 0.58 | 0.26 | 0.11 | |||
| rs2228480 | CC | 508 (69.02) | 41.5 (39.4-43.6) | 42.0 (40.3-43.8) | 46.3 (43.9-48.9) | 46.1 (43.8-48.5) | |
| CT | 207 (28.13) | 44.4 (41.1-47.7) | 43.4 (40.7-46.1) | 48.6 (44.7-52.6) | 46.9 (43.2-50.8) | ||
| TT | 21 (2.85) | 43.0 (32.6-53.4) | 47.3 (38.7-55.9) | 53.2 (40.9-67.2) | 56.6 (44.3-70.5) | ||
| Ptrend | 0.20 | 0.20 | 0.19 | 0.25 | |||
| ERβ | rs3829768 | TT | 733 (99.73) | 42.4 (40.6-44.1) | 42.6 (41.2-44.0) | 47.2 (45.1-49.3) | 46.7 (44.7-48.7) |
| TC | 2(0.27) | 30.3 (-3.4-64.0) | 16.5 (-11.2-44.2) | 45.6 (15.9-94.2) | 34.0 (10.6-74.7) | ||
| Ptrend | 0.48 | 0.07 | 0.94 | 0.48 | |||
| rs1256049 | GG | 688 (93.35) | 42.6 (40.8-44.4) | 42.8 (41.3-44.2) | 47.4 (45.3-49.6) | 46.9 (44.8-48.9) | |
| GA | 48 (6.51) | 38.9 (32.0-45.8) | 40.0 (34.3-45.6) | 44.2 (36.7-52.4) | 44.5 (37.3-52.5) | ||
| AA | 1 (0.14) | 43.0 (-4.7-90.7) | 54.1 (12.1-133.8) | ||||
| Ptrend | 0.33 | 0.35 | 0.50 | 0.57 | |||
| HSD17B1 | rs676387 | GG | 390 (52.92) | 42.2 (39.8-44.6) | 41.7 (39.8-43.7) | 46.2 (43.4-49.0) | 45.1 (42.5-47.8) |
| GT | 288 (39.08) | 42.8 (40.0-45.6) | 43.4 (41.1-45.7) | 48.4 (45.1-51.8) | 48.4 (45.2-51.7) | ||
| TT | 59 (8.01) | 40.1 (33.9-46.3) | 42.6 (37.4-47.9) | 46.4 (39.5-54.0) | 47.3 (40.4-54.8) | ||
| Ptrend | 0.83 | 0.39 | 0.53 | 0.20 | |||
| rs598126 | CC | 195 (26.64) | 41.2 (37.8-44.7) | 42.6 (39.8-45.5) | 48.2 (44.2-52.4) | 48.4 (44.5-52.5) | |
| CT | 354 (48.36) | 43.7 (41.1-46.2) | 43.1 (41.0-45.2) | 47.6 (44.6-50.6) | 46.6 (43.8-49.5) | ||
| TT | 183 (25.00) | 40.5 (37.0-44.1) | 41.0 (38.1-43.9) | 44.5 (40.6-48.6) | 44.3 (40.5-48.3) | ||
| Ptrend | 0.81 | 0.44 | 0.21 | 0.15 | |||
| rs2010750 | GG | 237 (32.29) | 41.9 (38.8-45.0) | 42.8 (40.3-45.4) | 47.7 (44.1-51.5) | 47.5 (44.0-51.1) | |
| GA | 351 (47.82) | 43.6 (41.0-46.1) | 43.1 (41.0-45.1) | 48.0 (45.0-51.1) | 47.3 (44.5-50.2) | ||
| AA | 146 (19.89) | 40.2 (36.3-44.2) | 41.0 (37.7-44.2) | 44.2 (39.9-48.8) | 44.0 (39.7-48.4) | ||
| Ptrend | 0.67 | 0.46 | 0.30 | 0.26 | |||
| COMT | rs4680 | GG | 190 (25.85) | 43.1 (39.6-46.6) | 42.4 (39.5-45.3) | 48.0 (44.0-52.2) | 47.7 (43.8-51.8) |
| GA | 375 (51.02) | 43.3 (40.8-45.8) | 43.8 (41.7-45.8) | 47.1 (44.3-50.1) | 46.5 (43.7-49.3) | ||
| AA | 170 (23.13) | 39.0 (35.3-42.6) | 39.6 (36.6-42.6) | 45.7 (41.6-50.1) | 45.4 (41.5-49.6) | ||
| Ptrend | 0.12 | 0.21 | 0.45 | 0.43 | |||
| CYP1B1 | rs1056836 | CC | 219 (29.72) | 43.7 (40.4-46.9) | 43.7 (41.0-46.3) | 49.6 (45.8-53.6) | 48.8 (45.2-52.6) |
| CG | 372 (50.47) | 42.3 (39.8-44.8) | 42.8 (40.8-44.8) | 46.7 (43.8-49.6) | 46.4 (43.7-49.2) | ||
| GG | 146 (19.81) | 40.2 (36.2-44.1) | 39.8 (36.6-43.1) | 44.2 (39.9-48.9) | 43.6 (39.4-48.0) | ||
| Ptrend | 0.18 | 0.09 | 0.07 | 0.08 | |||
a CI: confidence interval. b Means of absolute density are presented as back-transformed values.
c SNPs: single nucleotide polymorphisms. They are identified by their dbSNP accession number at http://www.ncbi.nlm.nih.gov/SNP/.
d N (%) values are slightly lower in adjusted models because of ten missing values in adjustment variables. e Adjusted for age at mammography, body mass index, waist-to-hip ratio, height, age at menarche, age at first birth, number of full-term pregnancies, breastfeeding, number of breast biopsies, family history of breast cancer, past contraceptive and hormone replacement therapy uses, smoking status, energy and alcohol intakes, physical activity and education. f P value is the P trend, testing genotype dosage, number of copies of the rare allele entered as 0, 1, 2 and mammographic density entered as continuous variable.