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Nuclear magnetic resonance-determined lipoprotein profile and risk of breast cancer: a Mendelian randomization study

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机构： [1]Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China [2]Department of Epidemiology and Biostatistics, West China‑PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China [3]Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China [4]Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China [5]Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China

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While crudely quantified lipoproteins have been reported to affect the risk of breast cancer, the effects of subclass lipoproteins characterized by particle size, particle number, and lipidomes remain unknown.Utilizing nuclear magnetic resonance-based GWAS of 85 lipoprotein traits, we performed two-sample univariable Mendelian randomization (MR) to evaluate the causal relationship between each trait with breast cancer (Ncase/control = 133,384/113,789) and with its estrogen receptor (ER) subtypes. Then, we applied multivariable MR to investigate the independent effects considering both general and central obesity.In univariable MR, a heterogeneous effect of subclass high-density lipoproteins (HDL) was observed, in which small HDL traits (ORs ranged from 0.89 to 0.94) were associated with a decreased risk of breast cancer while non-small HDLs traits (OR ranged from 1.04 to 1.08) were associated with an increased risk of breast cancer. Very-low-density lipoproteins (VLDL) traits and serum total triglycerides (TG) were associated with a decreased risk of breast cancer (ORs ranged from 0.88 to 0.94). Similar association patterns were found for ER + subtype. In multivariable MR, only the protective effects of small HDL, VLDL and TG on ER + subtype remained significant.We identified a heterogeneous effect of subclass HDLs and a consistent protective effect of VLDL on breast cancer. Only the effects of small HDL and VLDL on ER + subtype remained robust after controlling for obesity. These findings provide new insight into the causal pathway underlying lipoproteins and breast cancer.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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出版当年[2023]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

第一作者：

第一作者机构： [1]Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China [2]Department of Epidemiology and Biostatistics, West China‑PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China

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通讯作者：

通讯机构： [1]Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China [2]Department of Epidemiology and Biostatistics, West China‑PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China [3]Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China [5]Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China

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