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Cancer Epidemiology, Biomarkers & Prevention

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Research Articles

Endogenous Androgens and Risk of Epithelial Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

Sabina Rinaldi, Laure Dossus, Annekatrin Lukanova, Petra H.M. Peeters, Naomi E. Allen, Timothy Key, Sheila Bingham, Kay-Tee Khaw, Dimitrios Trichopoulos, Antonia Trichopoulou, Eleni Oikonomou, Guillem Pera, Nerea Larrañaga, Carmen Martinez-Garcia, Eva Ardanaz, J. Ramón Quirós, María-José Tormo, Anne Tjønneland, Anja Olsen, Kim Overvad, Jenny Chang-Claude, Jakob Linseisen, Mandy Schulz, Heiner Boeing, Carla H. van Gils, Bas H. Bueno-de-Mesquita, Valeria Pala, Domenico Palli, Salvatore Panico, Rosario Tumino, Paolo Vineis, Françoise Clavel-Chapelon, Sylvie Mesrine, Marie-Christine Boutron-Ruault, Eva Lundin, Åsa Ågren, Göran Berglund, Jonas Manjer, Merethe Kumle, Eiliv Lund, Nadia Slimani, Rodolfo Saracci, Elio Riboli and Rudolf Kaaks
Sabina Rinaldi
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Laure Dossus
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Annekatrin Lukanova
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Petra H.M. Peeters
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Naomi E. Allen
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Dimitrios Trichopoulos
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Nerea Larrañaga
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Carmen Martinez-Garcia
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Eva Ardanaz
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J. Ramón Quirós
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María-José Tormo
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Anne Tjønneland
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Anja Olsen
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Heiner Boeing
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Carla H. van Gils
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Bas H. Bueno-de-Mesquita
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Valeria Pala
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Domenico Palli
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Salvatore Panico
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Rosario Tumino
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Merethe Kumle
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Eiliv Lund
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DOI: 10.1158/1055-9965.EPI-06-0755 Published January 2007
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Tables

  • Table 1.

    Baseline characteristics of ovarian cancer cases and matched controls

    Premenopausal women
    Postmenopausal women
    Cases (n = 56)Controls (n = 109)pdiff*Cases (n = 136)Controls (n = 237)pdiff*
    Age at blood donation (y)46.1 (36.1-54.1)45.8 (37.4-53.0)60.9 (51.9-70.6)60.9 (52.1-71.5)
    Age at diagnosis (y)48.9 (39.0-60.0)——63.8 (54.0-74.0)——
    Time since blood donation (y)3.3 (0.2-7.6)——3.4 (0.6-7.6)——
    Height (cm)161.1 (152.0-172.0)161.0 (151.5-172.0)0.87159.4 (148.5-169.5)160.5 (149.0-171.5)0.03
    Weight (kg)68.6 (50.5-95.0)64.3 (50.0-85.3)0.0270.9 (52.3-94.0)70.2 (53.0-93.0)0.67
    BMI26.5 (20.7-35.8)24.8 (19.2-33.4)0.0227.9 (21.8-35.9)27.3 (20.2-37.2)0.18
    Waist (cm)82.0 (68.0-102.0)79.1 (66.0-96.0)0.0886.5 (69.0-106.0)86.3 (70.0-108.3)0.70
    Waist-to-hip ratio0.80 (0.70-0.95)0.79 (0.71-0.91)0.190.81 (0.72-0.92)0.83 (0.71-0.95)0.10
    Age at menarche (y)12.5 (11.0-15.0)12.8 (11.0-16.0)0.2113.7 (11.0-17.0)13.4 (11.0-16.0)0.13
    Parous76.890.80.01†81.686.10.21†
    Age at first full-term pregnancy (y)25.3 (20.0-32.0)25.2 (20.0-31.0)0.9725.4 (19.0-32.0)24.8 (18.0-32.0)0.08
    No. full-term pregnancy1.9 (1.0-3.0)2.1 (1.0-4.0)0.182.3 (1.0-5.0)2.5 (1.0-5.0)0.07
    Previous OC use58.963.30.53†28.732.90.35†
    OC use duration (y)4.4 (1.0-15.0)5.9 (1.0-30.0)0.145.9 (1.0-30.0)9.5 (1.0-30.0)0.11
    Previous HRT use———21.321.10.94†
    Age at menopause (y)———50.1 (43.0-56.0)49.4 (40.0-56.0)0.17
    Smoking status
        Never57.151.40.76†59.662.50.49†
        Former21.425.722.116.9
        Current21.422.918.419.8
    Ever had fertility problems5.44.60.78†0.72.10.34†
    Ever breast-feeding62.568.80.30†74.373.00.86†
    • NOTE: Mean (5th-95th percentiles) or percentages.

      Abbreviations: OC, oral contraceptive; HRT, hormone replacement therapy.

    • ↵* Paired t test.

    • ↵† χ2 test.

  • Table 2.

    Geometric means (and 95% confidence interval) of steroid hormones and SHBG for ovarian cancer case and control subjects by menopausal status at time of blood donation

    HormonePremenopausal women
    Postmenopausal women
    Case subjects (n = 56)Control subjects (n = 109)pdiff*Case subjects (n = 136)Control subjects (n = 237)pdiff*
    T (nmol/L)1.47 (1.30-1.66)1.40 (1.28-1.53)0.471.16 (1.06-1.26)1.20 (1.13-1.29)0.41
    fT (pmol/L)20.1 (17.1-23.7)18.2 (16.2-20.4)0.1516.2 (14.5-18.1)17.4 (15.9-18.9)0.27
    Δ4 (nmol/L)5.17 (4.66-5.75)4.99 (4.63-5.39)0.553.13 (2.90-3.37)3.34 (3.16-3.54)0.19
    DHEAS (μmol/L)3.26 (2.84-3.73)2.91 (2.64-3.21)0.231.78 (1.58-2.00)1.84 (1.68-2.01)0.82
    SHBG (nmol/L)46.6 (41.0-53.1)49.9 (45.4-54.8)0.4142.2 (38.6-46.3)42.6 (39.7-45.6)0.95
    • ↵* Paired t test.

  • Table 3.

    ORs of ovarian cancer (95% confidence intervals) by levels of sex steroids and SHBG in premenopausal women and their matched controls (in two exposure levels)

    Hormone concentration
    LowHighPassociationPtrend*
    T<1.42 nmol/L≥1.42 nmol/L
        Cases/controls23/4829/49
        Crude†1.001.27 (0.60-2.69)0.530.46
        Adjusted‡1.001.24 (0.57-2.71)0.590.78
        Adjusted§1.001.19 (0.52-2.74)0.680.97
    fT<18.5 pmol/L≥18.5 pmol/L
        Cases/controls22/4628/46
        Crude†1.001.42 (0.66-3.05)0.370.14
        Adjusted‡1.001.17 (0.53-2.58)0.710.48
        Adjusted§1.001.27 (0.56-2.89)0.570.51
    Δ4<4.90 nmol/L≥4.90 nmol/L
        Cases/controls26/5228/52
        Crude†1.001.11 (0.55-2.24)0.770.55
        Adjusted‡1.001.16 (0.56-2.41)0.690.45
        Adjusted§1.001.06 (0.49-2.30)0.870.63
    DHEAS<3.09 μmol/L≥3.09 μmol/L
        Cases/controls25/5431/55
        Crude†1.001.26 (0.63-2.51)0.520.20
        Adjusted‡1.001.22 (0.59-2.50)0.590.16
        Adjusted§1.001.20 (0.58-2.46)0.630.29
    SHBG<50.6 nmol/L≥50.6 nmol/L
        Cases/controls31/5123/51
        Crude†1.000.71 (0.36-1.41)0.330.29
        Adjusted‡1.000.95 (0.45-2.01)0.890.84
        Adjusted§1.000.97 (0.45-2.08)0.930.77
    • ↵* Linear trend on continuous (log transformed) variable.

    • ↵† Analysis matched on EPIC recruitment center, age at blood donation, phase of menstrual cycle, time of the day at blood donation, and fasting status.

    • ↵‡ Further adjustment for BMI.

    • ↵§ Further adjustment for ever having had a full-term pregnancy.

  • Table 4.

    ORs of ovarian cancer (95% confidence intervals) by tertiles of sex steroids and SHBG in postmenopausal women and their matched controls

    Tertiles
    Ptrend*Ptrend†
    123
    T<1.01 nmol/L1.01-1.45 nmol/L≥1.46 nmol/L
        Cases/controls41/6751/6833/68
        Crude‡1.001.15 (0.67-1.98)0.71 (0.37-1.36)0.340.33
        Adjusted§1.001.13 (0.65-1.94)0.68 (0.35-1.31)0.290.25
        Adjusted∥1.001.12 (0.65-1.93)0.69 (0.36-1.34)0.310.23
    fT<14.3 pmol/L14.3-23.6 pmol/L≥23.7 pmol/L
        Cases/controls54/6132/6132/64
        Crude‡1.000.63 (0.37-1.08)0.54 (0.29-0.98)0.030.19
        Adjusted§1.000.59 (0.34-1.02)0.45 (0.23-0.85)0.010.08
        Adjusted∥1.000.60 (0.35-1.04)0.45 (0.24-0.86)0.010.07
    Δ4<2.74 nmol/L2.74-3.85 nmol/L≥3.86 nmol/L
        Cases/controls46/7347/7335/76
        Crude‡1.000.99 (0.60-1.65)0.65 (0.37-1.14)0.150.14
        Adjusted§1.001.00 (0.60-1.66)0.66 (0.38-1.18)0.180.15
        Adjusted∥1.001.06 (0.63-1.79)0.67 (0.38-1.20)0.200.19
    DHEAS<1.52 μmol/L1.52-2.58 μmol/L≥2.59 μmol/L
        Cases/controls51/7740/7643/79
        Crude‡1.000.80 (0.47-1.37)0.81 (0.47-1.37)0.420.65
        Adjusted§1.000.81 (0.47-1.39)0.82 (0.48-1.40)0.460.71
        Adjusted∥1.000.82 (0.48-1.40)0.83 (0.49-1.41)0.480.74
    SHBG<36.3 nmol/L36.3-52.0 nmol/L≥52.1 nmol/L
        Cases/controls50/7035/7244/73
        Crude‡1.000.70 (0.41-1.18)0.84 (0.49-1.44)0.490.94
        Adjusted§1.000.72 (0.41-1.25)0.89 (0.48-1.62)0.670.65
        Adjusted∥1.000.73 (0.42-1.27)0.89 (0.49-1.63)0.690.63
    • ↵* Linear trends in ORs over the tertiles by scoring the categories according to the quantitative score 1, 2, and 3 for tertile categories.

    • ↵† Linear trend on continuous (log transformed) variable.

    • ↵‡ Analysis matched on EPIC recruitment center, age at blood donation, time of the day at blood donation, and fasting status.

    • ↵§ Further adjustment for BMI.

    • ↵∥ Further adjustment for ever having had a full-term pregnancy.

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Cancer Epidemiology Biomarkers & Prevention: 16 (1)
January 2007
Volume 16, Issue 1
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Endogenous Androgens and Risk of Epithelial Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
Sabina Rinaldi, Laure Dossus, Annekatrin Lukanova, Petra H.M. Peeters, Naomi E. Allen, Timothy Key, Sheila Bingham, Kay-Tee Khaw, Dimitrios Trichopoulos, Antonia Trichopoulou, Eleni Oikonomou, Guillem Pera, Nerea Larrañaga, Carmen Martinez-Garcia, Eva Ardanaz, J. Ramón Quirós, María-José Tormo, Anne Tjønneland, Anja Olsen, Kim Overvad, Jenny Chang-Claude, Jakob Linseisen, Mandy Schulz, Heiner Boeing, Carla H. van Gils, Bas H. Bueno-de-Mesquita, Valeria Pala, Domenico Palli, Salvatore Panico, Rosario Tumino, Paolo Vineis, Françoise Clavel-Chapelon, Sylvie Mesrine, Marie-Christine Boutron-Ruault, Eva Lundin, Åsa Ågren, Göran Berglund, Jonas Manjer, Merethe Kumle, Eiliv Lund, Nadia Slimani, Rodolfo Saracci, Elio Riboli and Rudolf Kaaks
Cancer Epidemiol Biomarkers Prev January 1 2007 (16) (1) 23-29; DOI: 10.1158/1055-9965.EPI-06-0755

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Endogenous Androgens and Risk of Epithelial Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
Sabina Rinaldi, Laure Dossus, Annekatrin Lukanova, Petra H.M. Peeters, Naomi E. Allen, Timothy Key, Sheila Bingham, Kay-Tee Khaw, Dimitrios Trichopoulos, Antonia Trichopoulou, Eleni Oikonomou, Guillem Pera, Nerea Larrañaga, Carmen Martinez-Garcia, Eva Ardanaz, J. Ramón Quirós, María-José Tormo, Anne Tjønneland, Anja Olsen, Kim Overvad, Jenny Chang-Claude, Jakob Linseisen, Mandy Schulz, Heiner Boeing, Carla H. van Gils, Bas H. Bueno-de-Mesquita, Valeria Pala, Domenico Palli, Salvatore Panico, Rosario Tumino, Paolo Vineis, Françoise Clavel-Chapelon, Sylvie Mesrine, Marie-Christine Boutron-Ruault, Eva Lundin, Åsa Ågren, Göran Berglund, Jonas Manjer, Merethe Kumle, Eiliv Lund, Nadia Slimani, Rodolfo Saracci, Elio Riboli and Rudolf Kaaks
Cancer Epidemiol Biomarkers Prev January 1 2007 (16) (1) 23-29; DOI: 10.1158/1055-9965.EPI-06-0755
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