Mendelian randomization analysis revealed potential metabolic causal factors for breast cancer
Abstract Observational studies showed that metabolic phenotypes were associated with the risk of developing breast cancer (BC). However, those results are inconsistent regarding the magnitude of the association, particularly by subtypes of breast cancer. Furthermore, the mechanisms of the associatio...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-41130-4 |
| _version_ | 1827634277517361152 |
|---|---|
| author | Mengshi Zhou Mason Henricks Valerie Loch Gloria Zhang Yong Lu Xiaoyin Li |
| author_facet | Mengshi Zhou Mason Henricks Valerie Loch Gloria Zhang Yong Lu Xiaoyin Li |
| author_sort | Mengshi Zhou |
| collection | DOAJ |
| description | Abstract Observational studies showed that metabolic phenotypes were associated with the risk of developing breast cancer (BC). However, those results are inconsistent regarding the magnitude of the association, particularly by subtypes of breast cancer. Furthermore, the mechanisms of the association remain unclear. We performed two-sample Mendelian randomization (MR) analyses to evaluate the causal effect of metabolic risk factors on breast cancer in the European population. Assessed individually using MR, body mass index (BMI) (odds ratio [OR] 0.94, 95% Confidence interval [CI] 0.90–0.98, P = 0.007), high-density lipoprotein cholesterol (HDL-C) (OR 1.10, 95% CI 1.07–1.13, P = 6.10 × 10–11) and triglycerides (TG) (OR 0.92, 95% CI 0.90–0.96, P = 1.58 × 10–6) were causally related to breast cancer risk. In multivariable MR, only HDL-C (OR 1.08; 95% CI 1.02–1.14; P = 0.02) retained a robust effect, suggesting that the genetic association between BMI, HDL-C and TG with breast cancer risk in univariable analysis was explained via HDL-C. These findings suggest a possible causal role of HDL-C in breast cancer etiology. |
| first_indexed | 2024-03-09T15:11:06Z |
| format | Article |
| id | doaj.art-bb342b39187d446ea26ccea90694cbab |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:11:06Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-bb342b39187d446ea26ccea90694cbab2023-11-26T13:22:17ZengNature PortfolioScientific Reports2045-23222023-08-0113111010.1038/s41598-023-41130-4Mendelian randomization analysis revealed potential metabolic causal factors for breast cancerMengshi Zhou0Mason Henricks1Valerie Loch2Gloria Zhang3Yong Lu4Xiaoyin Li5Department of Mathematics and Statistics, St. Cloud State UniversityDepartment of Mathematics and Statistics, St. Cloud State UniversityDepartment of Mathematics and Statistics, St. Cloud State UniversityDepartment of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland ClinicHouston Methodist Cancer Center/Weill Cornell MedicineDepartment of Mathematics and Statistics, St. Cloud State UniversityAbstract Observational studies showed that metabolic phenotypes were associated with the risk of developing breast cancer (BC). However, those results are inconsistent regarding the magnitude of the association, particularly by subtypes of breast cancer. Furthermore, the mechanisms of the association remain unclear. We performed two-sample Mendelian randomization (MR) analyses to evaluate the causal effect of metabolic risk factors on breast cancer in the European population. Assessed individually using MR, body mass index (BMI) (odds ratio [OR] 0.94, 95% Confidence interval [CI] 0.90–0.98, P = 0.007), high-density lipoprotein cholesterol (HDL-C) (OR 1.10, 95% CI 1.07–1.13, P = 6.10 × 10–11) and triglycerides (TG) (OR 0.92, 95% CI 0.90–0.96, P = 1.58 × 10–6) were causally related to breast cancer risk. In multivariable MR, only HDL-C (OR 1.08; 95% CI 1.02–1.14; P = 0.02) retained a robust effect, suggesting that the genetic association between BMI, HDL-C and TG with breast cancer risk in univariable analysis was explained via HDL-C. These findings suggest a possible causal role of HDL-C in breast cancer etiology.https://doi.org/10.1038/s41598-023-41130-4 |
| spellingShingle | Mengshi Zhou Mason Henricks Valerie Loch Gloria Zhang Yong Lu Xiaoyin Li Mendelian randomization analysis revealed potential metabolic causal factors for breast cancer Scientific Reports |
| title | Mendelian randomization analysis revealed potential metabolic causal factors for breast cancer |
| title_full | Mendelian randomization analysis revealed potential metabolic causal factors for breast cancer |
| title_fullStr | Mendelian randomization analysis revealed potential metabolic causal factors for breast cancer |
| title_full_unstemmed | Mendelian randomization analysis revealed potential metabolic causal factors for breast cancer |
| title_short | Mendelian randomization analysis revealed potential metabolic causal factors for breast cancer |
| title_sort | mendelian randomization analysis revealed potential metabolic causal factors for breast cancer |
| url | https://doi.org/10.1038/s41598-023-41130-4 |
| work_keys_str_mv | AT mengshizhou mendelianrandomizationanalysisrevealedpotentialmetaboliccausalfactorsforbreastcancer AT masonhenricks mendelianrandomizationanalysisrevealedpotentialmetaboliccausalfactorsforbreastcancer AT valerieloch mendelianrandomizationanalysisrevealedpotentialmetaboliccausalfactorsforbreastcancer AT gloriazhang mendelianrandomizationanalysisrevealedpotentialmetaboliccausalfactorsforbreastcancer AT yonglu mendelianrandomizationanalysisrevealedpotentialmetaboliccausalfactorsforbreastcancer AT xiaoyinli mendelianrandomizationanalysisrevealedpotentialmetaboliccausalfactorsforbreastcancer |