Association between triglyceride-glucose related indicators, genetic risk, and incident breast cancer among postmenopausal women in UK Biobank
Abstract Background The potential links between triglyceride-glucose (TyG) related indicators and breast cancer incidence after menopause have been less well studied, and the joint associations between genetic risk, TyG related indicators, and breast cancer are unknown. Methods Simple surrogate indi...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s12885-025-13970-y |
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| author | Zhen Li Zengle Zhao Tongchao Zhang Xiaorong Yang Hao Chen Xiaolin Yin Hao Bai Xinjie Liu Tongmin Chang Yuan Zhang Ming Lu |
| author_facet | Zhen Li Zengle Zhao Tongchao Zhang Xiaorong Yang Hao Chen Xiaolin Yin Hao Bai Xinjie Liu Tongmin Chang Yuan Zhang Ming Lu |
| author_sort | Zhen Li |
| collection | DOAJ |
| description | Abstract Background The potential links between triglyceride-glucose (TyG) related indicators and breast cancer incidence after menopause have been less well studied, and the joint associations between genetic risk, TyG related indicators, and breast cancer are unknown. Methods Simple surrogate indicators of insulin resistance including TyG, TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR), TyG-waist to hip ratio (TyG-WHR), TyG-body mass index (TyG-BMI). Genetic susceptibility in breast cancer was estimated by categorizing polygenic risk scores (PRS). For estimating the associations, we used Cox proportional hazards regression modeling. Correlation shapes were evaluated using restricted cubic splines (RCS). Mediation analyses for assessing the role of sex hormone-binding globulin (SHBG), C-reactive protein (CRP), testosterone, and glycosylated hemoglobin (HbA1c) in mediating the associations were conducted. Results The study included 83,873 UK biobank participants who were followed for a median of 13.8 years, with 3,561 new cases of postmenopausal breast cancer. Genetic risk and TyG related indicators were monotonically related to breast cancer, with additive but not multiplicative interactions between them. The highest quartiles of TyG, TyG-WC, TyG-WHtR, TyG-WHR, and TyG-BMI were significantly associated with increased breast cancer risk with hazard ratio (95% confidence interval) were 1.12 (1.01–1.25), 1.35 (1.23–1.49), 1.16 (1.05–1.28), 1.22(1.12–1.33), and 1.31 (1.19–1.44), respectively. TyG-WC was nonlinearly linked to breast cancer (P for nonlinear = 0.006). Individuals with high genetic risk and high TyG related indicators exhibited a substantially elevated breast cancer risk by 4- to 5-fold compared with reference group. The associations were mainly mediated by SHBG, CRP, and testosterone, with mediation proportions ranging from 10.24% to 68.29%. Conclusions TyG related factors are linked to incident postmenopausal breast cancer, and the combined effects with genetic risk significantly optimize risk stratification. High levels of TyG related indicators may amplify the influence of genetic factors on postmenopausal breast cancer. Trial registration Not applicable. |
| format | Article |
| id | doaj-art-29f5891bde20416187b44eecd3de54ef |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-29f5891bde20416187b44eecd3de54ef2025-08-20T03:15:13ZengBMCBMC Cancer1471-24072025-04-0125111410.1186/s12885-025-13970-yAssociation between triglyceride-glucose related indicators, genetic risk, and incident breast cancer among postmenopausal women in UK BiobankZhen Li0Zengle Zhao1Tongchao Zhang2Xiaorong Yang3Hao Chen4Xiaolin Yin5Hao Bai6Xinjie Liu7Tongmin Chang8Yuan Zhang9Ming Lu10Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong UniversityDepartment of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong UniversityClinical Epidemiology Unit, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Qilu Hospital of Shandong UniversityClinical Epidemiology Unit, Qilu Hospital of Shandong UniversityDepartment of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong UniversityDepartment of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong UniversityClinical Epidemiology Unit, Qilu Hospital of Shandong UniversityDepartment of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong UniversityAbstract Background The potential links between triglyceride-glucose (TyG) related indicators and breast cancer incidence after menopause have been less well studied, and the joint associations between genetic risk, TyG related indicators, and breast cancer are unknown. Methods Simple surrogate indicators of insulin resistance including TyG, TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR), TyG-waist to hip ratio (TyG-WHR), TyG-body mass index (TyG-BMI). Genetic susceptibility in breast cancer was estimated by categorizing polygenic risk scores (PRS). For estimating the associations, we used Cox proportional hazards regression modeling. Correlation shapes were evaluated using restricted cubic splines (RCS). Mediation analyses for assessing the role of sex hormone-binding globulin (SHBG), C-reactive protein (CRP), testosterone, and glycosylated hemoglobin (HbA1c) in mediating the associations were conducted. Results The study included 83,873 UK biobank participants who were followed for a median of 13.8 years, with 3,561 new cases of postmenopausal breast cancer. Genetic risk and TyG related indicators were monotonically related to breast cancer, with additive but not multiplicative interactions between them. The highest quartiles of TyG, TyG-WC, TyG-WHtR, TyG-WHR, and TyG-BMI were significantly associated with increased breast cancer risk with hazard ratio (95% confidence interval) were 1.12 (1.01–1.25), 1.35 (1.23–1.49), 1.16 (1.05–1.28), 1.22(1.12–1.33), and 1.31 (1.19–1.44), respectively. TyG-WC was nonlinearly linked to breast cancer (P for nonlinear = 0.006). Individuals with high genetic risk and high TyG related indicators exhibited a substantially elevated breast cancer risk by 4- to 5-fold compared with reference group. The associations were mainly mediated by SHBG, CRP, and testosterone, with mediation proportions ranging from 10.24% to 68.29%. Conclusions TyG related factors are linked to incident postmenopausal breast cancer, and the combined effects with genetic risk significantly optimize risk stratification. High levels of TyG related indicators may amplify the influence of genetic factors on postmenopausal breast cancer. Trial registration Not applicable.https://doi.org/10.1186/s12885-025-13970-yInsulin resistanceBreast cancerPolygenic risk scoreTyG indexObesity |
| spellingShingle | Zhen Li Zengle Zhao Tongchao Zhang Xiaorong Yang Hao Chen Xiaolin Yin Hao Bai Xinjie Liu Tongmin Chang Yuan Zhang Ming Lu Association between triglyceride-glucose related indicators, genetic risk, and incident breast cancer among postmenopausal women in UK Biobank BMC Cancer Insulin resistance Breast cancer Polygenic risk score TyG index Obesity |
| title | Association between triglyceride-glucose related indicators, genetic risk, and incident breast cancer among postmenopausal women in UK Biobank |
| title_full | Association between triglyceride-glucose related indicators, genetic risk, and incident breast cancer among postmenopausal women in UK Biobank |
| title_fullStr | Association between triglyceride-glucose related indicators, genetic risk, and incident breast cancer among postmenopausal women in UK Biobank |
| title_full_unstemmed | Association between triglyceride-glucose related indicators, genetic risk, and incident breast cancer among postmenopausal women in UK Biobank |
| title_short | Association between triglyceride-glucose related indicators, genetic risk, and incident breast cancer among postmenopausal women in UK Biobank |
| title_sort | association between triglyceride glucose related indicators genetic risk and incident breast cancer among postmenopausal women in uk biobank |
| topic | Insulin resistance Breast cancer Polygenic risk score TyG index Obesity |
| url | https://doi.org/10.1186/s12885-025-13970-y |
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