Body Fat Distribution and Risk of Breast, Endometrial, and Ovarian Cancer: A Two-Sample Mendelian Randomization Study
Background: Mounting evidence shows that adiposity increases female-specific cancer risk, but the role of body fat distribution is less clear. We used a two-sample Mendelian randomization (MR) approach to elucidate causal relations of body fat distribution to the risks of breast, endometrial and ova...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/20/5053 |
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| author | Dennis Freuer Jakob Linseisen Tracy A. O’Mara Michael Leitzmann Hansjörg Baurecht Sebastian-Edgar Baumeister Christa Meisinger |
| author_facet | Dennis Freuer Jakob Linseisen Tracy A. O’Mara Michael Leitzmann Hansjörg Baurecht Sebastian-Edgar Baumeister Christa Meisinger |
| author_sort | Dennis Freuer |
| collection | DOAJ |
| description | Background: Mounting evidence shows that adiposity increases female-specific cancer risk, but the role of body fat distribution is less clear. We used a two-sample Mendelian randomization (MR) approach to elucidate causal relations of body fat distribution to the risks of breast, endometrial and ovarian cancers and their subtypes. Methods: Body composition was assessed using segmental bioelectrical impedance analysis, yielding trunk, arm, and leg fat ratios (TFR, AFR, LFR) and BMI including 195,043 and 434,794 European women, respectively. The sample sizes for the outcomes ranged between 58,396 and 228,951. Causal effects were estimated per one standard deviation increment in the respective exposure within the radial regression framework. Robust sensitivity analyses were performed to verify MR assumptions. In a multivariable MR setting, the proportion of risk attributable to overall and abdominal fat content was assessed. Results: TFR, which represents abdominal fat content, was associated with ovarian cancer and its clear cell and endometrioid histotypes independent of overall fat content. BMI was inversely associated with breast cancer and its ER− and ER+ subtypes, but positively with endometrial cancer and ovarian cancer, including its endometrioid histotype. These estimates were confirmed using AFR as proxy for overall body fat. Conclusions: Visceral adiposity seems to be a driver of elevated ovarian cancer risk, particularly of the endometrioid and clear cell ovarian cancer histotypes. General adiposity decreases the risk of breast cancer but increases the risk of endometrial and ovarian cancer. |
| first_indexed | 2024-03-10T06:41:21Z |
| format | Article |
| id | doaj.art-5ad5ad95f21e403a9c8c2ba261c82684 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:41:21Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5ad5ad95f21e403a9c8c2ba261c826842023-11-22T17:39:31ZengMDPI AGCancers2072-66942021-10-011320505310.3390/cancers13205053Body Fat Distribution and Risk of Breast, Endometrial, and Ovarian Cancer: A Two-Sample Mendelian Randomization StudyDennis Freuer0Jakob Linseisen1Tracy A. O’Mara2Michael Leitzmann3Hansjörg Baurecht4Sebastian-Edgar Baumeister5Christa Meisinger6Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, 86156 Augsburg, GermanyChair of Epidemiology, University of Augsburg, University Hospital Augsburg, 86156 Augsburg, GermanyGenetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Brisbane 4006, AustraliaDepartment of Epidemiology and Preventive Medicine, University of Regensburg, 93053 Regensburg, GermanyDepartment of Epidemiology and Preventive Medicine, University of Regensburg, 93053 Regensburg, GermanyInstitute of Health Services Research in Dentistry, University of Münster, 48149 Münster, GermanyChair of Epidemiology, University of Augsburg, University Hospital Augsburg, 86156 Augsburg, GermanyBackground: Mounting evidence shows that adiposity increases female-specific cancer risk, but the role of body fat distribution is less clear. We used a two-sample Mendelian randomization (MR) approach to elucidate causal relations of body fat distribution to the risks of breast, endometrial and ovarian cancers and their subtypes. Methods: Body composition was assessed using segmental bioelectrical impedance analysis, yielding trunk, arm, and leg fat ratios (TFR, AFR, LFR) and BMI including 195,043 and 434,794 European women, respectively. The sample sizes for the outcomes ranged between 58,396 and 228,951. Causal effects were estimated per one standard deviation increment in the respective exposure within the radial regression framework. Robust sensitivity analyses were performed to verify MR assumptions. In a multivariable MR setting, the proportion of risk attributable to overall and abdominal fat content was assessed. Results: TFR, which represents abdominal fat content, was associated with ovarian cancer and its clear cell and endometrioid histotypes independent of overall fat content. BMI was inversely associated with breast cancer and its ER− and ER+ subtypes, but positively with endometrial cancer and ovarian cancer, including its endometrioid histotype. These estimates were confirmed using AFR as proxy for overall body fat. Conclusions: Visceral adiposity seems to be a driver of elevated ovarian cancer risk, particularly of the endometrioid and clear cell ovarian cancer histotypes. General adiposity decreases the risk of breast cancer but increases the risk of endometrial and ovarian cancer.https://www.mdpi.com/2072-6694/13/20/5053body fat distributionobesitybreast cancerendometrial cancerovarian cancerMendelian randomization |
| spellingShingle | Dennis Freuer Jakob Linseisen Tracy A. O’Mara Michael Leitzmann Hansjörg Baurecht Sebastian-Edgar Baumeister Christa Meisinger Body Fat Distribution and Risk of Breast, Endometrial, and Ovarian Cancer: A Two-Sample Mendelian Randomization Study Cancers body fat distribution obesity breast cancer endometrial cancer ovarian cancer Mendelian randomization |
| title | Body Fat Distribution and Risk of Breast, Endometrial, and Ovarian Cancer: A Two-Sample Mendelian Randomization Study |
| title_full | Body Fat Distribution and Risk of Breast, Endometrial, and Ovarian Cancer: A Two-Sample Mendelian Randomization Study |
| title_fullStr | Body Fat Distribution and Risk of Breast, Endometrial, and Ovarian Cancer: A Two-Sample Mendelian Randomization Study |
| title_full_unstemmed | Body Fat Distribution and Risk of Breast, Endometrial, and Ovarian Cancer: A Two-Sample Mendelian Randomization Study |
| title_short | Body Fat Distribution and Risk of Breast, Endometrial, and Ovarian Cancer: A Two-Sample Mendelian Randomization Study |
| title_sort | body fat distribution and risk of breast endometrial and ovarian cancer a two sample mendelian randomization study |
| topic | body fat distribution obesity breast cancer endometrial cancer ovarian cancer Mendelian randomization |
| url | https://www.mdpi.com/2072-6694/13/20/5053 |
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