Article Figures & Data
Figures
- Fig. 1.
COMT genotype and mammographic features. Values are least square means (±95% CI). All of the analyses are adjusted for age and ethnicity. In each genotype group, the number of subjects (n) are as follows: A, premenopausal group *1/*1, n = 45; group *1/*2, n = 98; group *2/*2, n = 38; B, postmenopausal group *1/*1, n = 46; group *1/*2, n = 79; group *2/*2, n = 46. a, b, ab, genotypes not sharing the same superscripts are significantly different, i.e., a and b are significantly different, but a and ab (or b and ab) are not significantly different (Bonferroni t test, P < 0.016).
, group *1/*1; □, group *1/*2;
, group *2/*2. - Fig. 2.
COMT genotype and anthropometric variables. Values are least square means (95% CI), and all of the analyses are adjusted for age and ethnicity. 1 Premenopausal subjects (n) of group *1/*1, n = 45; group *1/*2, n = 98; group *2/*2, n = 38 [n = 37 for subscapular skinfold (C)]. 2 Results (premenopausal) are further adjusted for GH, IGF-1, and IGFBP-3. A, BMI analyses are also adjusted for WHR; B, WHR analyses are also adjusted for BMI; C, subscapular skinfold analyses are also adjusted for BMI and WHR. Premenopausal group *1/*1, n = 44; group *1/*2, n = 96; group *2/*2, n = 37, except for subscapular skinfold (C), n = 36. 3 Postmenopausal group *1/*1, n = 46 except for subscapular skinfold (C), n = 45; group *1/*2, n = 79; group *2/*2, n = 46. 4 Postmenopausal group *1/*1, n = 42 except for subscapular skinfold (C), n = 41; group *1/*2, n = 69; group *2/*2, n = 43. a, b, ab, genotypes not sharing the same superscripts are significantly different, i.e. a and b are significantly different, but a and ab (or b and ab) are not significantly different (Bonferroni t test, P < 0.016).
, group *1/*1; □, group *1/*2;
, group *2/*2. - Fig. 3.
COMT genotype and percentage breast density adjusted individually and in combination for the GH-IGF-I axis, body size, and hormones. Values are least square means (± 95% CIs). Number of subjects in each genotype group: premenopausal group *1/*1, n = 44 for all analyses except age and ethnicity adjusted, for which n = 45; group *1/*2, n = 96 for all analyses except age and ethnicity adjusted, in which n = 98; group *2/*2, n = 37 in all analyses except age and ethnicity adjusted, in which n = 38. Postmenopausal group *1/*1, n = 42 in all analyses except age and ethnicity adjusted, in which n = 46; group *1/*2, n = 69 in all analyses except age and ethnicity adjusted, in which n = 79; group *2/*2, n = 43 in all analyses except age and ethnicity adjusted, in which n = 46. The three categories of variables are mutually adjusted (see results section, COMT Genotype, Body Size, Hormones, Growth Factors, and Mammographic Density for explanation). GH analyses (GH) adjusted for age, GH, IGF-1, and IGFBP-3. Body size analyses (BS) adjusted for age, BMI, and WHR. Hormones analyses (Horm) adjusted for age, FSH, and progesterone. a, b, ab, genotypes not sharing the same superscripts are significantly different, i.e. a and b are significantly different, but a and ab (or b and ab) are not significantly different (Bonferroni t test, P < 0.016).
, group *1/*1; □, group *1/*2;
, group *2/*2.
Tables
- Table 1
Selected characteristics of study subjects by menopausal status
Mean (SD) Caucasiana East Asianb Jewishc Otherd Pre n = 155 Pre n = 5 Pre n = 11 Pre n = 10 Post n = 141 Post n = 9 Post n = 5 Post n = 15 Premenopausal Risk factors Age, yr 44.7 (4.7) 47.4 (4.2) 45.6 (3.0) 45.5 (4.6) Height, cm 163.8 (6.1) 155.2 (6.3) 161.7 (5.1) 162.1 (10.4) Weight, kg 68.25 (16.2) 57.08 (5.9) 60.32 (10.6) 67.2 (15.3) BMI, kg/m2 25.4 (6.0) 23.6 (1.2) 23.0 (3.6) 25.6 (5.5) Waist:Hip ratio 0.75 (0.06) 0.75 (0.04) 0.73 (0.07) 0.75 (0.06) Age at menarche, yr 12.7 (1.4) 12.6 (2.7) 12.2 (0.6) 13.8 (1.4) Age at first birth, yr 28.1 (5.8) 33.3 (6.7) 29.5 (2.7) 24.4 (7.9) No. of live births 1.4 (1.2) 1.2 (1.1) 1.9 (1.4) 1.8 (1.3) Mammographic density, %e 28.0 (22.7) 49.7 (15.5) 37.0 (24.1) 22.1 (17.5) Pituitary hormones and growth factors Prolactin, μg/liter 16.3 (11.4) 22.0 (15.6) 12.8 (7.5) 25.2 (20.9) GH, μg/liter 1.7 (2.4) 2.6 (4.5) 2.5 (2.4) 3.6 (6.2) IGF-1, μg/liter 155.9 (35.8) 149.0 (33.7) 141 (35.0) 143.6 (23.5) IGFBP-3, mg/liter 2.7 (0.5) 2.6 (0.3) 2.7 (0.6) 2.6 (0.5) Sex hormones Estradiol, pmol/liter 321.2 (219.3) 172.4 (115.8) 239.2 (164.6) 361.5 (165.6) Free estradiol, % 2.2 (0.7) 1.9 (0.6) 1.9 (0.8) 2.3 (0.6) SHBG, nmol/liter 55.6 (26.1) 63.6 (21.9) 65.6 (27.8) 49.1 (20.3) Progesterone, nmol/liter 28.9 (22.7) 30.0 (31.4) 29.3 (21.6) 31.6 (20.0) FSH, IU/liter 9.3 (15.3) 20.7 (25.9) 10.3 (20.1) 7.2 (8.5) Postmenopausal Risk factors Age, yr 56.1 (4.7) 54.3 (3.3) 53.7 (2.3) 56.3 (4.1) Height, cm 164.9 (6.6) 157.1 (4.7) 164.7 (4.4) 162.2 (6.5) Weight, kg 71.7 (16.9) 56.4 (8.2) 69.0 (16.6) 65.3 (14.4) BMI, kg/m2 26.4 (6.1) 23.0 (3.9) 25.5 (6.2) 24.8 (5.2) Waist:Hip ratio 0.76 (0.08) 0.77 (0.07) 0.78 (0.10) 0.79 (0.06) Age at menarche, yr 13.1 (1.6) 12.9 (1.5) 12.7 (2.3) 12.9 (2.2) Age at first birth, yr 26.0 (5.2) 33.2 (7.1) 23.0 (3.3) 29.7 (8.1) No. of live births 1.7 (1.5) 1.3 (1.4) 2.2 (1.5) 1.2 (1.2) Mammographic density,e % 21.3 (19.4) 50.7 (11.5) 26.6 (24.3) 30.5 (21.6) Pituitary hormones and growth factors Prolactin, μg/liter 9.7 (5.6) 8.8 (3.7) 7.7 (3.1) 10.4 (3.4) GH, μg/liter 1.6 (2.6) 1.5 (2.4) 0.5 (0.4) 0.7 (0.8) IGF-1, μg/liter 128.2 (33.2) 137.2 (38.1) 133.5 (32.2) 142.9 (41.8) IGFBP-3, mg/liter 2.8 (0.5) 2.8 (0.5) 3.0 (0.5) 2.8 (0.6) Sex hormones Estradiol, pmol/liter 49.7 (98.8) 46.4 (42.4) 26.3 (10.2) 46.9 (32.2) Free estradiol, % 2.5 (0.6) 2.2 (0.7) 2.3 (0.6) 2.5 (0.5) SHBG, nmol/liter 42.5 (22.7) 52.1 (26.1) 48.3 (20.1) 41.7 (16.8) Progesterone, nmol/liter 1.7 (1.1) 1.7 (0.7) 1.6 (1.2) 2.1 (0.9) FSH, IU/liter 72.1 (30.7) 71.1 (23.2) 72.1 (11.1) 71.7 (31.3) -
a Premenopausal (Pre): n = 107 for age at first birth; n = 153 for GH; n = 154 for IGF-1, IGFBP-3, and free estradiol. Postmenopausal (Post): n = 104 for age at first birth; n = 127 for GH; n = 140 for IGF-1, IGFBP-3, free estradiol; n = 119 for total estradiol.
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b Pre: n = 3 for age at first birth. Post: n = 6 for age at first birth; n = 7 for GH; n = 8 for total estradiol, free estradiol, and SHBG.
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c Pre: n = 8 for age at first birth; n = 10 for GH. Post: n = 5 for age at first birth.
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d Pre: n = 8 for age at first birth. Post: n = 10 for age at first birth.
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e Proportion of breast area occupied by dense tissue.
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- Table 2
COMT genotype and allele frequency distribution
n COMT genotype distributiona Allele frequency *1/*1 *1/*2 *2/*2 COMT*1 COMT*2 Premenopausal All women 181 45 98 38 0.52 0.48 Caucasian 155 38 86 31 0.52 0.48 East Asian 5 2 2 1 0.60 0.40 Jewish 11 2 5 4 0.41 0.59 Other 10 3 5 2 0.55 0.45 Postmenopausal All women 171 46 79 46 0.50 0.50 Caucasian 141 28 71 42 0.45 0.55 East Asian 9 7 2 0 0.89 0.11 Jewish 6 2 2 2 0.50 0.50 Other 15 9 4 2 0.73 0.27 -
a COMT*1/*1 is associated with the high-activity phenotype, *1/*2 with the intermediate-activity phenotype, and *2/*2 with the low-activity phenotype.
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- Table 3
COMT genotype, sex hormones, and growth factors
Values are least square means (95% CI), and all of the models are adjusted for age and ethnicity. Results provided in italics have been further adjusted for BMI and WHR.a,b,ab
Premenopausal Postmenopausal Genotype F P Genotype F P *1/*1 n = 45c *1/*2 n = 98d *2/*2 n = 38e *1/*1 n = 46f *1/*2 n = 79g *2/*2 n = 46h Sex hormones Total estradiol 282.2 (209.9–365.3) 237.8 (180.1–303.4) 257.6 (185.5–341.5) 0.88 0.42 30.4 (24.6–38.4) 32.2 (25.9–41.4) 30.4 (24.6–38.4) 0.38 0.68 (pmol/liter) 291.0 (217.5–375.3) 241.5 (183.4–307.6) 242.7 (171.9–325.8) 1.11 0.33 30.7 (26.2–35.7) 33.9 (28.4–41.2) 32.9 (27.3–40.4) 0.58 0.56 Free estradiol (%) 2.02 (1.73–2.27) 2.19 (197–2.40) 2.21 (1.94–2.45) 1.28 0.28 2.58 (2.38–2.76) 2.37 (2.15–2.57) 2.40 (2.16–2.62) 1.90 0.15 2.14 (1.89–2.36) 2.23 (2.03–2.41) 2.13 (1.57–2.36) 0.62 0.54 2.57 (2.41–2.72) 2.40 (2.22–2.57) 2.53 (2.34–2.70) 2.16 0.12 SHBG (nmol/liter)j 62.3 (52.2–73.2) 55.5 (47.1–64.6) 54.5 (44.6–65.4) 1.28 0.28 39.6 (32.7–47.0) 46.0 (37.9–54.9) 46.8 (37.6–56.9) 1.39 0.25 57.9 (48.8–67.8) 54.0 (46.3–62.4) 58.2 (48.5–68.8) 0.67 0.51 39.9 (34.0–46.4) 45.3 (38.2–53.0) 42.1 (34.6–50.4) 1.16 0.32 Progesterone (nmol/liter)k 36.8 (29.2–45.4)a 25.0 (19.5–31.2)b 20.8 (14.9–27.7)b 9.17 0.0002 1.5 (1.2–1.8) 1.6 (1.3–2.0) 1.6 (1.3–2.0) 0.44 0.65 34.5 (27.3–42.5) a 24.3 (19.1–30.2) b 21.4 (15.6–28.1) b 6.81 0.001 1.5 (1.2–1.8) 1.6 (1.3–2.0) 1.6 (1.3–2.0) 0.32 0.73 FSH (IU/liter)l 6.8 (5.2–9.0)a 6.2 (4.9–7.9)ab 4.8 (3.6–6.4)b 2.98 0.05 64.1 (55.9–73.5) 61.0 (53.1–69.9) 73.0 (61.2–87.0) 2.69 0.07 6.4 (4.9–8.5) 6.0 (4.8–7.6) 4.9 (3.7–6.5) 1.61 0.20 63.8 (55.9–72.9) 61.2 (53.0–70.6) 69.5 (59.4–81.3) 1.56 0.21 Growth factors Prolactin (μg/liter) 16.1 (13.0–20.0) 14.3 (11.8–17.4) 16.0 (12.6–20.2) 0.97 0.38 8.0 (6.9–9.3) 8.7 (7.4–10.1) 8.3 (6.9–9.9) 0.49 0.61 16.0 (12.9–19.8) 14.3 (11.8–17.3) 15.7 (12.5–19.7) 0.87 0.42 8.0 (6.9–9.2) 8.5 (7.3–9.9) 7.9 (6.7–9.4) 0.52 0.60 GH (μg/liter)m 1.41 (0.85–2.34) 0.86 (0.56–1.33) 0.96 (0.56–1.64) 2.24 0.11 0.46 (0.30–0.72) 0.46 (0.29–0.72) 0.53 (0.32–0.88) 0.22 0.80 1.29 (0.78–2.11) 0.82 (0.53–1.25) 1.06 (0.62–1.81) 2.18 0.12 0.45 (0.29–0.69) 0.44 (0.28–0.69) 0.47 (0.29–0.78) 0.06 0.94 IGF-1 (μg/liter)n 159.0 (147.5–170.9)a 150.2 (140.5–160.1)a 136.9 (125.8–148.4)b 6.25 0.002 129.0 (119.2–139.2) 132.9 (122.5–143.7) 134.5 (122.9–146.6) 0.40 0.67 156.2 (145.4–167.3) a 148.6 (139.6–157.8) a 139.9 (129.2–151.1) b 3.51 0.03 129.0 (119.4–139.0) 134.3 (123.7–145.3) 132.2 (120.9–144.1) 0.44 0.65 IGFBP-3 mg/litero 2.53 (2.37–2.70)a 2.66 (2.52–2.80)ab 2.79 (2.61–2.97)b 3.83 0.02 2.77 (2.62–2.92) 2.85 (2.70–3.01) 2.73 (2.56–2.91) 1.27 0.28 2.58 (2.42–2.73) 2.68 (2.55–2.82) 2.73 (2.56–2.90) 1.70 0.19 2.76 (2.61–2.91) 2.82 (2.63–3.02) 2.72 (2.55–2.90) 0.80 0.45 -
a,b,ab Genotypes not sharing the same superscripts are significantly different, i.e., a and b are significantly different, but a and ab (or b and ab) are not significantly different (Bonferroni t test, P < 0.016).
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c n = 44 for free estradiol, GH, IGF-1, and IGFBP-3.
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d n = 97 for total estradiol, SHBG, and GH.
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e n = 37 for total estradiol, SHBG, GH, IGF-1, and IGFBP-3.
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f n = 43 for total estradiol and SHBG; n = 44 for free estradiol and FSH; n = 42 for GH, IGF-1, and IGFBP-3.
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g n = 62 for total estradiol and SHBG; n = 69 for GH, IGF-1, and IGFBP-3.
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h n = 40 for total estradiol and SHBG; n = 43 for GH, IGF-1, and IGFBP-3.
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i Adjusted for SHBG.
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j Adjusted for total estradiol levels.
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k Models adjusted for FSH.
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l Adjusted for progesterone levels in premenopausal women and for free estradiol values in postmenopausal women.
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m Adjusted for IGF-1 and IGFBP-3.
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n Adjusted for GH and IGFBP-3.
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o Adjusted for GH and IGF-1.
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Volume 12, Issue 9
