Inverse Association between Serum Total Cholesterol and Cancer Mortality in Dutch Civil Servants

Schuit, Albertine J.; Dijk, C.E.M.J. van; Dekker, J.M.; Schouten, E.G.; Kok, F.J.

doi:10.1093/oxfordjournals.aje.a116769

Cited by 58 publications

(32 citation statements)

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“…Cholesterol depletion prohibits the effect of chemotherapeutics by inhibition of membrane raft formation, because certain types of chemotherapeutic drugs require lipid raft-dependent death receptor activation for induction of cancer cell death (22,23). In addition, several epidemiological studies have reported an association of serum cholesterol levels at the lower end of the distribution with risk of cancer mortality (10,(24)(25)(26)(27). In this study, increased level of cholesterol led to markedly reduced viability and clonogenicity of stomach cancer cells.…”

Section: Discussionmentioning

confidence: 58%

Cholesterol induces autophagic and apoptotic death in gastric carcinoma cells

Lim

Parajuli

Duong

et al. 2014

International Journal of Oncology

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Abstract. Despite conflicting results, there is evidence to suggest an inverse link between total body cholesterol levels and the risk of certain malignancies. Based on previous reports, this phenomenon appears to vary with cancer site, and, in particular, more consistent data on inverse relations was reported in the risk of gastric cancer. In the current study, the effect of cholesterol on gastric cancer cell viability was examined using an in vitro cell culture system. Addition of cholesterol in culture medium resulted in reduced viability and clonogenicity of SNU601, SNU638 and SNU216 gastric cancer cells by induction of both autophagic and apoptotic death. Transient inactivation of ERK1/2 was linked to reduction of cholesterol-mediated cell viability, and tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2/DR5) was also involved in cell death signaling. In conclusion, these results imply that cholesterol can act as a signal regulator to modulate cell viability and that proper cellular cholesterol levels may be advantageous to suppress growth of gastric carcinomas.

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Section: Discussionmentioning

confidence: 58%

Cholesterol induces autophagic and apoptotic death in gastric carcinoma cells

Lim

Parajuli

Duong

et al. 2014

International Journal of Oncology

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“…The nature of associations between cancer and lipids remains controversial. Large epidemiological studies of general population suggest an inverse total cholesterolcancer relationship (Schatzkin et al 1987, Schuit et al 1993, Steenland et al 1995. In support of these findings, we further identified the threshold value of total cholesterol !4.30 mmol/l for the inverse total cholesterol-cancer relationship in T2DM.…”

Section: Discussionmentioning

confidence: 99%

Predicting values of lipids and white blood cell count for all-site cancer in type 2 diabetes

Yang

So²,

Ma³

et al. 2008

Endocrine Related Cancer

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Type 2 diabetic patients have increased cancer risk. We developed and validated an all-site cancer risk score in a prospective cohort of 7374 Chinese type 2 diabetic patients free of known history of cancer at enrolment, using split-half validation. Spline Cox model was used to detect common risk factors of cancer and to guide linear transformation of non-linear risk factors. After a median follow-up period of 5.45 years, 365 patients (4.95%) developed cancer. Body mass index (BMI; !24.0 or R27.6 kg/m 2 ), triglyceride (R0.81 to !1.41 mmol/l), high-density lipoprotein cholesterol (!0.9 or R1.8 mmol/l), total cholesterol (!4.3 mmol/l) and white blood cell (WBC) count (!5.8!10 9 count per litre) were associated with increased cancer risks and exhibited non-linear relationships. We further linear transformed these terms for selection using backward Cox regression (P!0.05 for stay) in the training dataset. In the test dataset, calibration was checked using Hosmer-Lemeshow test and discrimination checked using area under receiver operating characteristic curve. In addition to age and current smoking, only linear-transformed total cholesterol and WBC count were selected. The risk score was 0.0488!age (years)K0.5810!total cholesterol (mmol/l, coded to 4.3 if O4.3)K0.3596!WBC count (10 9 counts/l, 5.8 if O5.8)C0.6390!current smoking status (1 if yes). The 5-year probability of cancer was 1K0.9590 EXP(0.9382!(RISK SCOREC1.5903)) .The predicted cancer probability was not significantly different from the observed cancer probability during the 5-year follow-up. The adjusted area under receiver operating characteristic curve was 0.712. In conclusion, BMI, lipids and WBC count have predicting values for cancer.

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“…Tornberg et al (19) observed that total cancer incidence and mortality were inversely correlated to serum cholesterol level. The association between serum total cholesterol and cancer mortality was also investigated in a 28-year follow-up study of Dutch middleaged civil servants and their spouses (20). The investigators suggested that low serum cholesterol might be a risk factor for cancer mortality in men.…”

Section: Discussionmentioning

confidence: 99%

Total Cholesterol and Body Mass Index in Relation to 40-Year Cancer Mortality (The Corfu Cohort of the Seven Countries Study)

Panagiotakos

Pitsavos

Polychronopoulos

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Purpose: We evaluated risk factors of cancer mortality based on a 40-year follow-up of the Corfu cohort (Seven Countries Study). Material and Methods: The population studied in this analysis consisted of 529 rural men (49 F 6 years old) enrolled in 1961. Since then, periodic visits every 5 years were made to define the causes of death of the participants. Cox proportional hazards models evaluated various risk factors in relation to cancer mortality. Results: The death rate at the end of the follow-up was 87.1% (i.e., 461 deaths in 529 participants). Of those deaths, 118 (25.6%) were because of cancer (30 deaths were due to cancer of trachea, bronchus, and lung, and the rest were due to other malignant neoplasms). Cancer was the second cause of death in this cohort, after coronary heart disease. Age (hazard ratio, 1.05 per year; P < 0.05), smoking (hazard ratio, 1.97; P < 0.01), total serum cholesterol levels (hazard ratio, 0.95 per 10 mg/dL; P < 0.05), and body mass index (hazard ratio, 0.93 per 1 kg/m 2 ; P < 0.05) showed a significant association with cancer deaths after controlling for physical activity status and anthropometric indices. It should be noted that the protective effect of total cholesterol on cancer mortality was observed only between 183 and 218 mg/dL baseline levels. Conclusion: Cancer was one of the leading causes of death in this cohort. Smoking was associated with increased risk of cancer, whereas moderate total serum cholesterol and increased body and mass index seemed to have a protective effect on 40-year cancer mortality. (Cancer Epidemiol Biomarkers Prev 2005;14(7):1797 -801)

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Inverse Association between Serum Total Cholesterol and Cancer Mortality in Dutch Civil Servants

Cited by 58 publications

References 0 publications

Cholesterol induces autophagic and apoptotic death in gastric carcinoma cells

Cholesterol induces autophagic and apoptotic death in gastric carcinoma cells

Predicting values of lipids and white blood cell count for all-site cancer in type 2 diabetes

Total Cholesterol and Body Mass Index in Relation to 40-Year Cancer Mortality (The Corfu Cohort of the Seven Countries Study)

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