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Maternal height and breast cancer risk: results from a study nested within the EPIC-Greece cohort

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Abstract

The positive association of adult height with breast cancer (BC) risk has been hypothesized to be partly accounted for by an association of this risk with maternal height (operating in utero to modify hormone effects). In a case–control study (271 BC patients and 791 controls) nested within the EPIC-Greece cohort, we applied mediation analysis to calculate the direct and indirect (through the woman’s own height) effect of maternal height on BC risk. Per 5 cm increase in maternal height and depending on its reference value: the indirect effect odds ratio ranges from 1.02 to 1.07; the direct effect odds ratio from 1.06 to 1.11; and the total (direct and indirect effects) from 1.08 to 1.19. The effect sizes consistently increased for higher reference categories of maternal height, but did not generally reach statistical significance, possibly due to the limited sample size.

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Acknowledgements

The study was supported by the Hellenic Health Foundation. CLV was partly supported by the Italian Foundation for Research on Cancer (FIRC).

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Authors and Affiliations

  1. Hellenic Health Foundation, 13 Kaisareias and Alexandoupoleos Street, 115 27, Athens, Greece

    Michail Katsoulis, Carlo La Vecchia, Antonia Trichopoulou & Pagona Lagiou

  2. Farr Institute of Health Informatics Research, University College London, 222 Euston Road, London, NW1 2DA, UK

    Michail Katsoulis

  3. Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via Vanzetti, 5, 20133, Milan, Italy

    Carlo La Vecchia

  4. Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 75 M. Asias Street, Goudi, 115 27, Athens, Greece

    Pagona Lagiou

  5. Department of Epidemiology, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

    Pagona Lagiou

Authors
  1. Michail Katsoulis
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  2. Carlo La Vecchia
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  3. Antonia Trichopoulou
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  4. Pagona Lagiou
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Corresponding author

Correspondence to Antonia Trichopoulou.

Appendix

Appendix

Study population

Though anthropometric measurements (including height) were performed and recorded for the volunteers in EPIC-Greece (11,953 men/16,619 women) [11], no information was recorded on the height of the participants’ mothers. As collection of this information for all women recruited in EPIC-Greece was impractical, we conducted a matched case–control study nested within EPIC-Greece and collected information on maternal height in a subsample of the women in the cohort through telephone interviews. We included all breast cancer cases diagnosed either before or after their recruitment in the cohort. Each breast cancer case was matched to three control women, who had not developed any type of cancer. Matching criteria were age at recruitment (±1 year) and date of enrollment (±6 months).

Cases and controls had to be alive at the time of interview on maternal height. Of the 524 cases, 436 (96%) respectively, were alive at the time of the interview. The percentage of those who didn’t answer or declined to participate was 33% (144 individuals) for the cases and we tried to find up to 3 controls for them (the percentage of non-repliers in controls was about the same with the cases, but we tried to substitute the non-repliers). We collected information from 1136 women and, after excluding 74 participants (6%) with missing information in any of the covariates used in our analyses, we ended up with 271 breast cancer cases (110 prevalent and 161 incident cases) and 791 controls. Moreover, 60 out of the 271 breast cancer cases were only self-reported canes and not confirmed through hospital records).

Data collection

Socio-demographic and lifestyle characteristics, such as educational level, physical activity, smoking status, as well as information related to age at menarche, menopausal status and parity, were recorded at enrollment in the EPIC-Greece cohort. Recording frequency and duration of participation in physical activities [11] allowed the calculation of a metabolic equivalent index (MET value) for each activity [12] and eventually of an overall MET × hour sum, indicating the amount of energy per kilogram of body weight expended during an average day by each participant. Dietary habits were also recorded at enrollment, with the use of a validated interviewer-administered semi-quantitative food frequency questionnaire [13]. Anthropometric measurements were undertaken using standardized procedures [14]. Body weight was measured to the nearest 100 g, and height was measured to the nearest 1 cm. Body mass index (BMI) was calculated as the ratio of weight over the square of height (in kg/m2).

Data on maternal height were collected through telephone interviews conducted from July to September 2012. Women were asked to classify their mother’s height in comparison to their own height in one of five categories: shorter by 8 cm or more, 3–7 cm shorter, approximately the same height (±2 cm), 3–7 cm taller, taller by 8 cm or more. They were also asked to give an estimation of their mother’s height in cm.

Table 3 Logistic regression derived beta coefficients (95% confidence intervals) for breast cancer mutually adjusted for the indicated variables
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Table 4 Linear regression-derived beta coefficients (95% confidence interval) for a woman’s own height by maternal height controlling for the indicated variables; estimated among control women for 5 cm increase in the woman’s own height
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Sensitivity analyses

See Tables 5, 6, 7, 8 and 9.

Table 5 Conditional natural direct, indirect and total effects of maternal height on breast cancer risk, expressed as odds ratios (95% confidence intervals) per 5 cm increase in maternal height, at different reference levels of maternal height, among participants for whom the information on height collected in categories was consistent with that provided as exact height (1001 of the 1062 of the participants, i.e. 94%)
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Table 6 Conditional natural direct, indirect and total effects of maternal height on breast cancer risk, expressed as odds ratios (95% confidence intervals) per 5 cm increase in maternal height, at different reference levels of maternal height, for incident breast cancer cases and the corresponding controls
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Table 7 Conditional natural direct, indirect and total effects of maternal height on breast cancer risk, expressed as odds ratios (95% confidence intervals) per 5 cm increase in maternal height, at different reference levels of maternal height among post-menopausal women only
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Table 8 Conditional natural direct, indirect and total effects of maternal height on breast cancer risk, expressed as odds ratios (95% confidence intervals) per 5 cm increase in maternal height, at different reference levels of maternal height, without adjusting for any of the potential confounders (see Table 2)
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Table 9 Conditional natural direct, indirect and total effects of maternal height on breast cancer risk, expressed as odds ratios (95% confidence intervals) per 5 cm increase in maternal height, at different reference levels of maternal height, among confirmed breast cancer cases and the corresponding controls (841 of the 1062 of the participants, i.e. 79%)
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Katsoulis, M., La Vecchia, C., Trichopoulou, A. et al. Maternal height and breast cancer risk: results from a study nested within the EPIC-Greece cohort. Eur J Epidemiol 32, 457–463 (2017). https://doi.org/10.1007/s10654-017-0245-z

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  • DOI: https://doi.org/10.1007/s10654-017-0245-z

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