Is cholesterol a risk factor for breast cancer incidence and outcome?

Hassen, Céline Ben; Goupille, Caroline; Vigor, Claire; Guéraud, Françoise; Silvente-Poirot, Sandrine; Poirot, Marc; Frank, Philippe G.

doi:10.1016/j.jsbmb.2023.106346

Cited by 11 publications

(5 citation statements)

References 171 publications

(208 reference statements)

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“…These effects are primarily exerted through regulating the structure and function of cell membranes, cellular homeostasis, and hormone synthesis. 47 , 48 , 49 Therefore, with reference to the optimization of TyG‐neck circumference (TyG‐NC), TyG‐neck circumference to height ratio (TyG‐NHtR), TyG‐waist circumference (TyG‐WC), TyG‐waist to height ratio (TyG‐WHtR), TyG‐body mass index (TyG‐BMI), 22 we optimized TyG‐BMI, and the product of TyG‐BMI and TC/HDL‐c was used as the GLMI. The level of IR in PC patients with diabetes was evaluated using GLMI.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of glucose‐lipid metabolic index in pancreatic cancer patients with diabetes mellitus

Wang,

Ruan,

et al. 2024

Cancer Medicine

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BackgroundThe incidence of pancreatic cancer (PC) is higher in diabetic patients due to disturbances in glucose and lipid metabolism caused by insulin resistance (IR). However, the effect of diabetes as well as IR on the prognosis of PC patients remains inconclusive. Our study aims to assess the impact of IR on the prognosis of PC patients with diabetes.MethodsWe conducted a retrospective analysis of 172 PC patients with diabetes in our institute from 2015 to 2021. Prognostic assessment was performed using univariate/multifactorial analysis and survival analysis. The predictive efficacy of metabolic indices was compared using receiver operator characteristic (ROC) curve analysis.ResultsOne hundred twenty‐one of 172 patients died during follow‐up, with a median follow‐up of 477 days and a median overall survival (OS) of 270 days. Survival analysis showed a significant difference in OS by IR related parameters, which were triglyceride‐glucose index (TyG), triglyceride‐glucose index‐body mass index (TyG‐BMI), and triglyceride/high‐density lipoprotein cholesterol ratio (TG/HDL‐c). The ROC curve indicated that TyG, TyG‐BMI, and TG/HDL‐c had prognostic efficacy for PC with diabetes. We next optimized TyG‐BMI and obtained a new parameter, namely glucose‐lipid metabolism index (GLMI), and the patients were classified into GLMI low group and high group based on the calculated cutoff value. The GLMI high group had higher TyG, TyG‐BMI, TyG/HDL‐c, BMI, TG, total cholesterol (TC), TC/HDL‐c, fasting plasma glucose, CA199, and more advanced tumor stage compared to low group. Univariate and multivariate analyses showed that GLMI was an independent prognostic factor. Furthermore, the patients of GLMI high group had worse OS compared to low group and the ROC curves showed GLMI had better predictive ability than TyG and TyG‐BMI.ConclusionsIR is associated with the outcome of PC patients with diabetes and higher level of IR indicates worse prognosis. GLMI has a good predictive value for PC with diabetes.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of glucose‐lipid metabolic index in pancreatic cancer patients with diabetes mellitus

Wang,

Ruan,

et al. 2024

Cancer Medicine

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“…The reduced level of serum cholesterol was another cancer-related feature observed in our study, though this effect was milder in patients with breast cancer compared to other cancers. Nevertheless, reduced levels of cholesterol may result from the fact that cholesterol is a key precursor of estrogen (45). Moreover, cholesterol-reach LDLs impact the proliferation of breast cancer cells due to the overexpression of Akt and ERK pathway intermediates (46), and high expression of LDL receptors was detected in breast cancer cells (47).…”

Section: Discussionmentioning

confidence: 99%

Profiling of serum metabolome of breast cancer: multi-cancer features discriminate between healthy women and patients with breast cancer

Mrowiec,

Debik,

Jelonek

et al. 2024

Front. Oncol.

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IntroductionThe progression of solid cancers is manifested at the systemic level as molecular changes in the metabolome of body fluids, an emerging source of cancer biomarkers.MethodsWe analyzed quantitatively the serum metabolite profile using high-resolution mass spectrometry. Metabolic profiles were compared between breast cancer patients (n=112) and two groups of healthy women (from Poland and Norway; n=95 and n=112, respectively) with similar age distributions.ResultsDespite differences between both cohorts of controls, a set of 43 metabolites and lipids uniformly discriminated against breast cancer patients and healthy women. Moreover, smaller groups of female patients with other types of solid cancers (colorectal, head and neck, and lung cancers) were analyzed, which revealed a set of 42 metabolites and lipids that uniformly differentiated all three cancer types from both cohorts of healthy women. A common part of both sets, which could be called a multi-cancer signature, contained 23 compounds, which included reduced levels of a few amino acids (alanine, aspartate, glutamine, histidine, phenylalanine, and leucine/isoleucine), lysophosphatidylcholines (exemplified by LPC(18:0)), and diglycerides. Interestingly, a reduced concentration of the most abundant cholesteryl ester (CE(18:2)) typical for other cancers was the least significant in the serum of breast cancer patients. Components present in a multi-cancer signature enabled the establishment of a well-performing breast cancer classifier, which predicted cancer with a very high precision in independent groups of women (AUC>0.95).DiscussionIn conclusion, metabolites critical for discriminating breast cancer patients from controls included components of hypothetical multi-cancer signature, which indicated wider potential applicability of a general serum metabolome cancer biomarker.

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“…However, observational studies on the relationship between circulating CHOL and breast cancer risk have provided inconclusive or sometimes contradictory results. While some systematic reviews and meta-analyses suggest that dietary CHOL intake and serum CHOL levels are associated with breast cancer risk [59,60], other prospective studies have found no significant or inverse association [61][62][63]. Confounding variables such as obesity, menopausal status, tumor subtype, and ER status may be the reason for these conflicting results.…”

Section: Cholesterol Biosynthesis and Breast Cancer Initiation And De...mentioning

confidence: 99%

Impact of De Novo Cholesterol Biosynthesis on the Initiation and Progression of Breast Cancer

Coradini

2024

Biomolecules

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Cholesterol (CHOL) is a multifaceted lipid molecule. It is an essential structural component of cell membranes, where it cooperates in regulating the intracellular trafficking and signaling pathways. Additionally, it serves as a precursor for vital biomolecules, including steroid hormones, isoprenoids, vitamin D, and bile acids. Although CHOL is normally uptaken from the bloodstream, cells can synthesize it de novo in response to an increased requirement due to physiological tissue remodeling or abnormal proliferation, such as in cancer. Cumulating evidence indicated that increased CHOL biosynthesis is a common feature of breast cancer and is associated with the neoplastic transformation of normal mammary epithelial cells. After an overview of the multiple biological activities of CHOL and its derivatives, this review will address the impact of de novo CHOL production on the promotion of breast cancer with a focus on mammary stem cells. The review will also discuss the effect of de novo CHOL production on in situ and invasive carcinoma and its impact on the response to adjuvant treatment. Finally, the review will discuss the present and future therapeutic strategies to normalize CHOL biosynthesis.

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Is cholesterol a risk factor for breast cancer incidence and outcome?

Cited by 11 publications

References 171 publications

Prognostic significance of glucose‐lipid metabolic index in pancreatic cancer patients with diabetes mellitus

Prognostic significance of glucose‐lipid metabolic index in pancreatic cancer patients with diabetes mellitus

Profiling of serum metabolome of breast cancer: multi-cancer features discriminate between healthy women and patients with breast cancer

Impact of De Novo Cholesterol Biosynthesis on the Initiation and Progression of Breast Cancer

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