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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Research Articles

The Heritability of Mammographically Dense and Nondense Breast Tissue

Jennifer Stone, Gillian S. Dite, Anoma Gunasekara, Dallas R. English, Margaret R.E McCredie, Graham G. Giles, Jennifer N. Cawson, Robert A. Hegele, Anna M. Chiarelli, Martin J. Yaffe, Norman F. Boyd and John L. Hopper
Jennifer Stone
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Gillian S. Dite
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Anoma Gunasekara
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Dallas R. English
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Margaret R.E McCredie
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Graham G. Giles
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Jennifer N. Cawson
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Robert A. Hegele
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Anna M. Chiarelli
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Martin J. Yaffe
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Norman F. Boyd
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John L. Hopper
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DOI: 10.1158/1055-9965.EPI-05-0127 Published April 2006
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    Figure 1.

    Examples of a dense breast (left) and a nondense breast (right).

  • Figure 2.
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    Figure 2.

    Distribution of the absolute area of dense breast tissue (A) and absolute area of nondense breast tissue (B) by age at mammogram. Black dot, median; box widths, 1st and 3rd quartiles; whiskers, 1.5 times the interquartile range; lines outside the whiskers, outliers. If the notches on two boxes do not overlap, this indicates a difference in a location at a rough 5% significance level.

  • Figure 3.
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    Figure 3.

    A. Variation in the log of dense breast tissue area (left y axis) and estimates of correlation of the log of dense breast tissue area for MZ and DZ pairs (right y axis) by age at mammogram. B. Variation in the log of nondense breast tissue area (left y axis) and estimates of correlation of the log of nondense breast tissue area for MZ and DZ pairs (right y axis) by age at mammogram.

Tables

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  • Table 1.

    Characteristics of monozygous and dizygous female twin subjects

    Monozygous (n = 571), mean (SE)Dizygous (n = 380), mean (SE)
    Age at interview (y)50.72 (0.33)53.03 (0.38)
    Age at mammogram (y)50.65 (0.32)52.55 (0.38)
    Time between interview and mammogram (mo)6.29 (0.23)6.14 (0.28)
    Weight (kg)66.18 (0.50)67.87 (0.61)
    Height (cm)162.00 (0.26)162.97 (0.32)
    Age at menarche (y)13.04 (0.06)12.93 (0.07)
    Age at first birth (y; parous women only)24.88 (0.14)25.07 (0.17)
    No. live births2.31 (0.05)2.42 (0.06)
    Years of oral contraceptive use6.04 (0.22)5.87 (0.27)
    Years of hormone replacement therapy2.46 (0.17)2.05 (0.21)
    Pack-years of smoking5.58 (0.43)6.97 (0.52)
    PMD37.82 (0.79)35.69 (0.96)
    Absolute dense area of mammographic tissue (cm2)40.50 (0.96)38.33 (1.17)
    Absolute nondense area of mammographic tissue (cm2)78.60 (2.03)84.78 (2.47)
    Total area of the breast (cm2)119.14 (1.98)123.05 (2.40)
    Parous (% yes)84.685.9
    Cessation of periods (% stopped)59.355.0
  • Table 2.

    Estimates (SE) of residual variance (σ2), of monozygous and dizygous covariances (σmonozygous2 and σdizygous2, respectively), of monozygous and dizygous correlations (ρmonozygous and ρdizygous, respectively), and of heritability (H) under the AE model on log dense area and log dense area, separately

    EstimateAge adjusted for meanMean adjusted for age and covariates*Random effect a function of age†
    Log dense area
        σ20.63 (0.023)0.60 (0.022)0.43 + 0.015 (age 40)
        σmonozygous20.43 (0.025)0.39 (0.024)0.31 + 0.007 (age 40)
        σdizygous20.16 (0.030)0.13 (0.029)0.09 + 0.004 (age 40)
        ρmonozygous0.67 (0.021)0.66 (0.022)0.73 − 0.005 (age 40)
        ρdizygous0.25 (0.046)0.21 (0.047)0.21 + 0.001 (age 40)
        H0.66 (0.022)0.65 (0.024)0.71 (0.039)
        −2 Log-likelihood668.1585.8531.8
    Log nondense area
        σ20.45 (0.017)0.24 (0.0089)0.28 − 0.004 (age 40)
        σmonozygous20.34 (0.018)0.16 (0.0096)0.19 − 0.002 (age 40)
        σdizygous20.15 (0.021)0.05 (0.012)0.06 − 0.001 (age 40)
        ρmonozygous0.76 (0.017)0.67 (0.022)0.67 − 0.0002 (age 40)
        ρdizygous0.34 (0.042)0.21 (0.044)0.23 − 0.002 (age 40)
        H0.75 (0.017)0.66 (0.023)0.67 (0.036)
        −2 Log-likelihood−162.7−1,165.3−1,178.8
    • ↵* Adjusted covariates for mean log dense area were age, height, weight, age at menarche, number of live births, years of oral contraception use, years of hormone replacement therapy use, menopausal status, and population (Australian vs North American). Adjusted covariates for mean log nondense area were age, height, weight, age at menarche, number of live births, age at first birth, pack years of smoking, and population (Australian vs North American).

    • ↵† These analyses allowed the random effects variables to vary as a linear function of age (centered on 40 y).

  • Table 3.

    Estimates (SE) of the cross-trait correlation between dense and nondense area in the same individual and the cross-trait cross-twin correlation between dense area in one twin and nondense area in the other twin

    Bivariate model: log dense and log nondenseCorrelation in same individualCross-correlation
    Monozygous pairsDizygous pairs
    Mean adjusted for age−0.35 (0.023)−0.26 (0.026)−0.14 (0.034)
    Mean adjusted for age and covariates−0.31 (0.023)−0.20 (0.027)−0.08 (0.036)
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Cancer Epidemiology Biomarkers & Prevention: 15 (4)
April 2006
Volume 15, Issue 4
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The Heritability of Mammographically Dense and Nondense Breast Tissue
Jennifer Stone, Gillian S. Dite, Anoma Gunasekara, Dallas R. English, Margaret R.E McCredie, Graham G. Giles, Jennifer N. Cawson, Robert A. Hegele, Anna M. Chiarelli, Martin J. Yaffe, Norman F. Boyd and John L. Hopper
Cancer Epidemiol Biomarkers Prev April 1 2006 (15) (4) 612-617; DOI: 10.1158/1055-9965.EPI-05-0127

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The Heritability of Mammographically Dense and Nondense Breast Tissue
Jennifer Stone, Gillian S. Dite, Anoma Gunasekara, Dallas R. English, Margaret R.E McCredie, Graham G. Giles, Jennifer N. Cawson, Robert A. Hegele, Anna M. Chiarelli, Martin J. Yaffe, Norman F. Boyd and John L. Hopper
Cancer Epidemiol Biomarkers Prev April 1 2006 (15) (4) 612-617; DOI: 10.1158/1055-9965.EPI-05-0127
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