Associations between serum lipids and breast cancer incidence and survival in the E3N prospective cohort study

His, Mathilde; Dartois, Laureen; Fagherazzi, Guy; Boutten, Anne; Dupré, Thierry; Mesrine, Sylvie; Boutron‐Ruault, Marie‐Christine; Clavel‐Chapelon, Françoise; Dossus, Laure

doi:10.1007/s10552-016-0832-4

Cited by 41 publications

(50 citation statements)

References 34 publications

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“…The inverse association between triglycerides and breast cancer risk in comprehensive MR was abolished after excluding variants associated with other lipids, implying that triglyceride levels do not affect breast cancer risk independently. This result broadly concurs with observational studies that reported either absent or weak inverse associations 6 , 7 , 27 .…”

Section: Discussionsupporting

confidence: 91%

A Mendelian randomization study of the effects of blood lipids on breast cancer risk

2018

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Observational studies have reported inconsistent associations between circulating lipids and breast cancer risk. Using results from >400,000 participants in two-sample Mendelian randomization, we show that genetically raised LDL-cholesterol is associated with higher risk of breast cancer (odds ratio, OR, per standard deviation, 1.09, 95% confidence interval, 1.02–1.18, P = 0.020) and estrogen receptor (ER)-positive breast cancer (OR 1.14 [1.05–1.24] P = 0.004). Genetically raised HDL-cholesterol is associated with higher risk of ER-positive breast cancer (OR 1.13 [1.01–1.26] P = 0.037). HDL-cholesterol-raising variants in the gene encoding the target of CETP inhibitors are associated with higher risk of breast cancer (OR 1.07 [1.03–1.11] P = 0.001) and ER-positive breast cancer (OR 1.08 [1.03–1.13] P = 0.001). LDL-cholesterol-lowering variants mimicking PCSK9 inhibitors are associated (P = 0.014) with lower breast cancer risk. We find no effects related to the statin and ezetimibe target genes. The possible risk-promoting effects of raised LDL-cholesterol and CETP-mediated raised HDL-cholesterol have implications for breast cancer prevention and clinical trials.

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Section: Discussionsupporting

confidence: 91%

A Mendelian randomization study of the effects of blood lipids on breast cancer risk

2018

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“…27HC and circulating cholesterol are well correlated in our data (r = 0.45). On balance, prior studies do not support a strong association between circulating cholesterol and breast cancer risk [18] or survival [19,20], with an inverse association reported between total and HDL cholesterol and risk in a meta-analysis [18] and postmenopausal women in the current study population [8]. Cholesterol-lowering drug use and breast cancer risk (predominantly statins) [21,22] and survival [10,23,24] have been investigated with cholesterol-lowering medications, again mainly statins, proposed as a strategy to improve prognosis [24].…”

Section: Discussionmentioning

confidence: 90%

Circulating 27-hydroxycholesterol and breast cancer tissue expression of CYP27A1, CYP7B1, LXR-β, and ERβ: results from the EPIC-Heidelberg cohort

et al. 2020

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Background: Experimental and epidemiological studies demonstrate a role for 27-hydroxycholesterol (27HC) in breast cancer development, though results are conflicting. Cholesterol 27-hydroxylase (CYP27A1) and oxysterol 7alpha-hydroxylase (CYP7B1) regulate 27HC concentrations, while differential expression of the liver X receptor (LXR) and estrogen receptor beta (ERβ) may impact the association between 27HC and breast cancer risk. Methods: We evaluated correlates of tumor tissue expression of CYP27A1, CYP7B1, LXR-β, and ERβ and the association between circulating prediagnostic 27HC concentrations and breast cancer risk by marker expression in a nested casecontrol study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort including 287 breast cancer cases with tumor tissue available. Tumor protein expression was evaluated using immunohistochemistry, and serum 27HC concentrations quantified using liquid chromatography-mass spectrometry. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A higher proportion of CYP7B1-positive cases were progesterone receptor (PR)-positive, relative to CYP7B1negative cases, whereas a higher proportion of ERβ-positive cases were Bcl-2 low, relative to ERβ-negative cases. No differences in tumor tissue marker positivity were observed by reproductive and lifestyle factors. We observed limited evidence of heterogeneity in associations between circulating 27HC and breast cancer risk by tumor tissue expression of CYP27A1, CYP7B1, LXR-β, and ERβ, with the exception of statistically significant heterogeneity by LXR-β status in the subgroup of women perimenopausal at blood collection (p = 0.02). Conclusion: This exploratory study suggests limited associations between tumor marker status and epidemiologic or breast cancer characteristics. Furthermore, the association between circulating 27HC and breast cancer risk may not vary by tumor expression of CYP27A1, CYP7B1, LXR-β, or ERβ.

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“…Although some 4 But, studies contradict. 5 Recently, the body mass index (BMI) has been shown to be distributed differently to the breast cancer molecular subtypes, 6 and has also been supported by others. 7,8 Triglycerides serve as an independent source for fatty acid oxidation, 9 an important process that supports the carcinogenic potential of triglycerides and promotes cell proliferation and tumor growth.…”

Section: Introductionmentioning

confidence: 84%

Increased Lipids Levels and Breast Cancer

Parlak¹,

Kocaöz

2019

Online Türk Sağlık Bilimleri Dergisi

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Breast cancer is the top cancer in women both in the developed and the developing world. Metabolic heterogeneity may be present in all cancers. Dyslipidemia is independently associated with the development of breast cancer. The present study was carried out on serum samples from 100 breast cancer patients named study group and 100 similar age normal women named control group. Lipid pattern studies were carried out on study group and control group before any treatment. The serum samples so collected were examined for Total cholesterol (TC), High density lipoprotein cholesterol (HDL), Low density lipoprotein cholesterol (LDL) and Triglyceride (TG) concentrations. In the study group the youngest patient was of 35 years old and oldest patient was of 83 years. Mean age was 58.41±11.01 years. In the control group, the youngest patient was of 30 years and oldest patient was of 80 years. TC, LDL, TG levels increased in all grades, which is similar in the of C-ERB-B2 positive status. Our study supports the relationship between increased lipid levels and breast cancer. However, there is a need for multiple center studies, including prospective, to be used as a marker.

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Associations between serum lipids and breast cancer incidence and survival in the E3N prospective cohort study

Abstract: Our results suggest that serum lipids are not associated with breast cancer risk overall, but that menopausal status and waist circumference should be considered in further studies.

Cited by 41 publications

References 34 publications

A Mendelian randomization study of the effects of blood lipids on breast cancer risk

A Mendelian randomization study of the effects of blood lipids on breast cancer risk

Circulating 27-hydroxycholesterol and breast cancer tissue expression of CYP27A1, CYP7B1, LXR-β, and ERβ: results from the EPIC-Heidelberg cohort

Increased Lipids Levels and Breast Cancer

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