Changes in serum lipids and lipoproteins in cancer patients during chemotherapy

Summary We studied serum lipid and lipoprotein changes occurring during chemotherapy in 57 patients with chemosensitive cancers, including 18 malignant lymphomas, 18 breast carcinomas, 14 small-cell lung carcinomas, and 7 urothelial-cell carcinomas. Patients who responded favorably to chemotherapy demonstrated a significant increase in serum total cholesterol and LDL cholesterol values, with the singular exception of breastcancer patients, who exhibited a nonsignificant decrease in both of these parameters. Serum levels of free cholesterol and HDL cholesterol did not show any significant changes. Finally, serum triglycerides tended to increase after effective chemotherapy, but this was of statistical significance only in breast-cancer patients. Although our findings were based on a rather small number of patients, they indicate that the lipid and lipoprotein disorders reported in cancer patients are reversible by effective treatment of the tumor, suggesting that these disorders are a secondary phenomenon of malignancy.     

恶性肿瘤患者血清皮质醇激素变化致癌因性疲乏及其机制研究

  目的  探讨恶性肿瘤患者血清皮质醇激素水平变化与癌因性疲乏的相关性及其机制。  方法  80例恶性肿瘤患者分为疲乏组（50例疲乏患者）和非疲乏组（30例非疲乏患者）,利用多维疲乏症状量表-简化版（MFSI-SF）和疲劳症状量表（FSI）对患者进行评估。电化学发光法检测血清皮质醇的水平,酶联免疫吸附法测定血清促肾上腺皮质激素（ACTH）的水平,COD-PAP法测定血清胆固醇浓度,双缩脲法测定血清总蛋白、白蛋白浓度,琼脂糖凝胶电泳测定α2-球蛋白比值并计算血清α2-球蛋白浓度。  结果  疲乏组患者血清皮质醇水平低于非疲乏组[（119.68±5.34）nmol/L vs.（163.45±31.49）nmol/L,P < 0.05],促肾上腺皮质激素水平高于非疲乏组[（104.50±17.15）ng/L vs.（51.43±13.24）ng/L,P < 0.05]。疲乏组患者MFSI-SF评分与血清皮质醇激素水平呈负相关（r=-0.867,P < 0.001）,与血清促肾上腺皮质激素水平呈正相关（r=0.809,P < 0.001）;疲乏组患者FSI评分与血清皮质醇激素水平呈负相关（r=-0.747,P < 0.001）,与血清促肾上腺皮质激素水平呈正相关（r=0.701,P < 0.001）。疲乏组患者血清胆固醇[（1.25±0.70）mmol/L vs.（3.28±0.73）mmol/L,P < 0.05]、白蛋白[（18.24±7.03）g/L vs.（37.40±8.05）g/L,P < 0.05]和α2球蛋白水平明显低于非疲乏组[（2.25±1.07）g/L vs.（5.36±1.09）g/L,P < 0.05]。  结论  疲乏组患者癌因性疲乏评分增高,而血清皮质醇激素水平降低,促肾上腺皮质激素水平升高;恶性肿瘤患者机体低血清皮质醇激素导致促肾上腺皮质激素紊乱和癌因性疲乏的发生,血清皮质醇激素降低的机制与其合成原料血清胆固醇及其运载蛋白（白蛋白特别是α2球蛋白）降低有关。      

Low serum cholesterol levels predict inferior prognosis and improve NCCN‐IPI scoring in diffuse large B cell lymphoma

Low circulating cholesterol concentration is associated with elevated cancer incidence and mortality. However, the association between cholesterol levels and diffuse large B cell lymphoma (DLBCL) remains unknown. The aim of our study was to evaluate the prognostic value of serum lipid profile in DLBCL. Five hundred and fifty enrolled subjects with detailed serum lipid levels at diagnosis of DLBCL were randomly divided into a training set (n = 367) and a validation set (n = 183) (ratio, 2:1). Multivariate Cox regression analyses screened the prognostic factors associated with progression‐free survival (PFS) and overall survival (OS). Performances of models were compared using C‐index and area under the curve in internal and external validation. The results showed that decreased levels of total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) were associated with unfavorable PFS and OS in the rituximab era, and concurrently low HDL‐C together with low LDL‐C was an independent prognostic indicator for both PFS and OS. Patients achieving complete remission or partial remission after 6–8 circles of chemotherapies had significantly increased cholesterol levels compared to the levels at DLBCL diagnosis, and HDL‐C or LDL‐C elevations were correlated with better survival. Furthermore, the predictive and discriminatory capacity of the National Comprehensive Cancer Network (NCCN)‐International Prognostic Index (IPI) together with low cholesterol levels was superior to NCCN‐IPI alone both in the training and validation set. In conclusion, serum cholesterol levels are simple and routinely tested parameters, which may be good candidates for predicting prognosis in the future clinical practice of DLBCL.     

Tamoxifen treatment reverses the adverse effects of chemotherapy-induced ovarian failure on serum lipids

In all, 146 premenopausal women with early stage breast cancer were treated with adjuvant chemotherapy. In addition, 5-year tamoxifen treatment was started after chemotherapy to those 112 patients with hormone-receptor-positive tumours while those with hormone-receptor-negative tumours received no further therapy. The serum lipid levels were followed in both groups. The levels of serum total and low-density lipoprotein (LDL) cholesterol increased significantly after chemotherapy only in patients who developed ovarian dysfunction. Total cholesterol increased +9.5% and LDL cholesterol +16.6% in patients who developed amenorrhoea (P<0.00001 and 0.00001, respectively). The cholesterol levels did not change in patients who preserved regular menstruation after chemotherapy. After 6 months of tamoxifen therapy, the total cholesterol decreased -9.7% and the LDL cholesterol -16.7% from levels after the chemotherapy, while the cholesterol concentrations remained at increased levels in the control group (P=0.001 and P<0.0001, respectively). The high-density lipoprotein cholesterol levels did not change significantly in either tamoxifen or control group. The effects of tamoxifen treatment on serum lipids after chemotherapy have not been studied before. Our current study suggests that adjuvant tamoxifen therapy reverses the adverse effects of chemotherapy-induced ovarian failure on total and LDL cholesterol and even lowers their serum levels below the baseline.     

Changes in serum lipid and lipoprotein levels in postmenopausal patients with node-positive breast cancer treated with tamoxifen

Tamoxifen has been used for a long time as an adjuvant hormonal treatment in breast cancer patients. We studied 62 newly diagnosed postmenopausal women, aged 50-79 years, with node-positive breast cancer and receiving adjuvant tamoxifen (20 mg per day). Total serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, apo AI, apo AII, apo B and Lp(a) were determined before the surgery and 3, 6, 9, 12 and 24 months after starting tamoxifen treatment. Tamoxifen significantly reduced total serum cholesterol (6.13+/-1.20 mmol/L vs 5.21+/-1.05 mmol/L) (P <0.01), LDL-cholesterol (3.72+/-0.70 mmol/L vs 2.93+/-0.51) (P <0.01) and Lp(a) (0.11+/-0.07 g/L vs 0.02+/-0.01 g/L) (P < 0.01). There were no changes in triglycerides or HDL-cholesterol serum levels during tamoxifen treatment. The results indicate that an additional beneficial effect of adjuvant tamoxifen therapy may be that it decreases cardiovascular risk in such patients.     

The association of lipoprotein cholesterol with vitamin A

Several studies have linked total serum cholesterol concentrations below 200 mg/dl with increased cancer risk, especially among men. Cancer risk appears to be associated primarily with low concentrations of total cholesterol and of low-density lipoprotein cholesterol but not of high-density lipoprotein cholesterol (HDL). It has been suggested that low concentrations of total cholesterol are associated with increased cancer risk indirectly by virtue of their association with low concentrations of carotene and/or retinol. The relationship between serum carotene and cholesterol in a biracial group of 146 first-year college students was investigated. White men and women had similar carotene concentrations. Blacks had higher serum carotene concentrations than whites. There was a significant relationship between carotene concentrations and total cholesterol, which was most evident in men, both black (r = +0.72; P less than 0.01) and white (r = +0.49; P less than 0.01). The correlations for the women were significant, but of lower magnitude than for the men. Significant carotene-HDL relationships were observed among black men (r = 0.31; P less than 0.05) and among women (r = 0.35; P less than 0.05 and r = 0.31; P less than 0.05, black and white, respectively). Furthermore, the women also demonstrated a significant carotene-HDL2 association. The results are consistent with the hypothesis that the association between low serum cholesterol concentrations and cancer may be the result of a relationship between lipoprotein cholesterol concentrations and vitamin A metabolism.     

Serum lipids and lipoprotein disorders in cancer patients

Total serum cholesterol, free and esterified cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, serum triglycerides and serum lipoproteins were measured in 103 consecutive cancer patients (60 men and 43 women; mean age, 56 years) and 100 age-matched noncancer inpatients. Cancer patients as a group demonstrated significantly lower total cholesterol, esterified cholesterol and LDL cholesterol, compared with noncancer patients. Breast cancer proved to be an exception associated with increased serum total cholesterol, free cholesterol, LDL cholesterol, and triglycerides. a-lipoproteins were constantly increased in cancer patients whereas no differences were found in the other lipoprotein fractions. Finally, the observed overall incidence of hyperlipidemia in cancer patients (23/103) was not significantly different from the controls (29/100).     

The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L).

BACKGROUND: The purpose of this study was to evaluate changes in serum lipid parameters {cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and lipoprotein(a) [Lp(a)]}, in postmenopausal women receiving letrozole or placebo after adjuvant tamoxifen for early stage breast cancer (NCIC CTG MA.17L). PATIENTS AND METHODS: MA.17L is a substudy of MA.17, a randomized, double-blind, placebo-controlled trial of letrozole 2.5 mg taken daily for 5 years in postmenopausal women with primary breast cancer completing approximately 5 years of prior adjuvant tamoxifen. Patients consenting to participate in this companion study had blood drawn and lipid parameters (total cholesterol, HDL cholesterol, LDL cholesterol, Lp(a), triglycerides) evaluated at baseline, 6 months, 12 months and yearly thereafter until completion of protocol therapy. It was required that women be non-hyperlipidemic and not taking lipid-lowering drugs at time of entry on this trial. RESULTS: Three hundred and forty seven women were enrolled in the study. The letrozole and the placebo groups demonstrated marginally significant differences in the percentage change from baseline in HDL cholesterol at 6 months (P=0.049), in LDL cholesterol at 12 months (P=0.033) and triglycerides at 24 months (P=0.036). All comparisons of lipid parameters at other time points were not significantly different between the two treatment groups. No statistically significant differences in the number of patients exceeding the thresholds defined for the lipid parameters were found between the two treatment groups. CONCLUSIONS: The MA.17 trial demonstrated a significant improvement in disease-free survival with the use of letrozole as extended adjuvant therapy post tamoxifen. Results from this study suggests that letrozole does not significantly alter serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or Lp(a) in non-hyperlidiemic postmenopausal women with primary breast cancer treated up to 36 months following at least 5 years of adjuvant tamoxifen therapy. These findings further support the tolerability of extended adjuvant letrozole in postmenopausal women following standard tamoxifen therapy.     

Relationship between vitamin E and polyunsaturated fatty acids in breast cancer. Nutritional and metabolic aspects

Intake of vitamin E, total lipids, total cholesterol, and fatty acids were analyzed with the blood levels of vitamin E, total cholesterol, triglycerides, and the serum distribution of fatty acids in a hospital-based population of 120 patients and 109 controls. In regard to nutritional intake, the only significant differences involve saturated and monounsaturated fatty acid consumption, which is more elevated in postmenopausal patients than in postmenopausal controls. Vitamin E and total cholesterol blood levels are significantly higher in patients than in controls, where the difference is that vitamin E is independent from cholesterol level in premenopausal women only. Fatty acid serum distribution is comparable in both samples, with the exception of arachidonic acid, which is significantly lower in premenopausal patients than in premenopausal controls. Two multivariate regression analyses of the plasma vitamin E levels of patients and controls were done with menopausal status and nutrients as independent variables for the first analysis, and with menopausal status and all blood analytes for the second one. The regression coefficients for total cholesterol and triglycerides are statistically significant for both samples, whereas a positive association between vitamin E plasma level and sunflower oil consumption and between vitamin E plasma level and serum linoleic acid distribution is significant for patients only. Furthermore, the multiple regression shows that, when adjusted for analyte variables, plasma vitamin E levels are higher in premenopausal than in postmenopausal patients. In addition, plasma lipid peroxidation, evaluated by malondialdehyde measurement, is shown to be significantly lower in patients than in controls. Malondialdehyde level is associated with a significant lower odds ratio (OR) after multivariate tertile analysis (OR for the highest tertile: 0.51; 95% CI: 0.29-0.89). Together, these findings are consistent with a picture of lower lipid peroxidation in patients than in controls.     

结直肠癌术后辅助化疗对血脂变化的影响

目的:探讨结直肠癌患者术后辅助化疗前后血脂水平的变化及不同化疗方案对血脂变化的影响。方法:对127例结直肠癌患者术后辅助化疗前后总胆固醇（TC）、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)水平进行测定并比较分析。结果:化疗后,TG、HDL、LDL水平较化疗前升高,差异有统计学意义（P＜0.05）。TC值较化疗前增高,但差异无统计学意义（P＞0.05）。含奥沙利铂的化疗方案与卡培他滨单药方案相比对TC、TG、LDL的影响更加显著,差异有统计学意义（P＜0.05）。结论:结直肠癌患者在术后辅助化疗期间存在血脂代谢紊乱,以血清TG、HDL、LDL升高为特点;不同化疗方案对血脂变化的影响存在差异。     

Cholesterol, weight, height, Quetelet's index, and colon cancer recurrence

The association of low serum cholesterol with colon cancer mortality suggests that low serum cholesterol promotes colon cancer recurrence. We compared cumulative 5-year recurrence-free rates of 279 colon cancer patients in relation to serum cholesterol, weight, height, and Quetelet's index. The median value for each variable was used to divide patients into those above the median, or at the median and below. Patients with median and lower serum cholesterol exhibited an 11% lower disease-free rate at 5 years. Patients above median weight were at significantly increased risk of recurrence in both sexes (76 vs 54%, z = 3.0026, p = 0.003). Progressively decreasing weight was noted with advancing stage in males but not in females. Women above median Quetelet's index were also at significantly greater risk of recurrence (74 vs 52%, z = 2.6109, p = 0.009). Patients above median height were at insignificantly increased risk of recurrence. This study indicates that body weight is a significant prognostic factor for patients with colon cancer.     

初治时血脂水平对小细胞肺癌患者预后的影响

目的探讨初治时血脂水平对小细胞肺癌(SCLC)患者预后的影响。方法回顾性分析2012—2017年吉林大学第一医院收治的129例SCLC患者的临床资料,根据中国人群血脂合适水平与异常分层标准,按初治时血脂即总胆固醇、甘油三酯、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇进行分组,分析不同血脂水平与SCLC患者临床特征和预后的关系。结果 129例SCLC患者中,初治时总胆固醇<5.2 mmol/L 90例(69.8%),≥5.2 mmol/L 39例(30.2%);甘油三酯<1.7 mmol/L 95例(73.6%),≥1.7 mmol/L 34例(26.4%);高密度脂蛋白胆固醇<1.0 mmol/L 27例(20.9%),≥1.0 mmol/L 102例(79.1%);低密度脂蛋白胆固醇<3.4 mmol/L 90例(69.8%),≥3.4 mmol/L 39例(30.2%)。初治时甘油三酯水平与SCLC患者的体质指数有关(P<0.05)。SCLC患者的甘油三酯水平、临床分期与患者的中位无进展生存时间有关(均P<0.05),SCLC患者的临床分期与患者的中位总生存时间有关(P<0.05)。初治时甘油三酯<1.7 mmol/L患者的中位无进展生存时间为10.5个月,明显长于初治时甘油三酯≥1.7 mmol/L的患者(8.8个月,P=0.024)。初治时甘油三酯<1.7 mmol/L患者的中位总生存时间为20.2个月,虽长于初治时甘油三酯≥1.7 mmol/L的患者(15.6个月),但差异并无统计学意义(P=0.097)。多因素分析结果显示,初治时甘油三酯水平升高是SCLC进展的独立危险因素(P=0.022)。初治时总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇与SCLC的预后无明显相关性(均P>0.05)。结论初治时甘油三酯水平是影响SCLC患者预后的独立因素,其水平升高提示疾病进展快,预后差。     

Serum lipids in vertigo and sensorineural deafness

The study shows that the serum lipid value increases in vertigo and sensorineural deafness cases. The study was carried out in twenty vertigo and fifteen sensorineural deafness patients with a control group of 20 cases in the age group of 30–70 years. The present study indicates that the serum cholesterol, serum phospholipid, and serum triglycerides are the major serum lipids which show a significant rise in blood levels. The serum cholesterol, serum phospholipid and triglyceride levels in vertigo cases are significantly higher when analysed statistically as the ‘p’ value is less than 0.05 while the other lipids are not raised significantly as the ‘P’ value is more than 0.05. Similarly in sensorineural deafness patients the raised serum cholesterol, phospholipid and triglyceride levels are highly significant as the ‘P’ value is lower than 0.01 when analysed statistically. In sensorineural deafness patients the serum uric acid is raised significantly when analysed statistically. Serum lipid studies are not only important from the diagnostic point of view but also for prognosis too. Serum lipid studies should be carried out in all patients of vertigo and sensorineural deafness as a preliminary test. Once a raised serum lipid level is established, the main treatment is by dietic control.     

Fasting plasma lipid measurements following cisplatin chemotherapy in patients with germ cell tumors.

PURPOSE: Elevated total serum cholesterol levels have been reported recently in a group of patients with metastatic testicular cancer after treatment with cisplatin combination chemotherapy. We have studied the lipid profile of a similar group of patients in an attempt to confirm this observation. PATIENTS AND METHODS: Fasting plasma lipid concentrations were measured in 47 patients with advanced germ cell tumors who were previously treated with a cisplatin combination chemotherapy. The values obtained for mean total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein A1, and apolipoprotein B concentrations were compared with those obtained from a control group of 59 patients with germ cell tumors who were not treated with chemotherapy and with data from the New Zealand male population. Median time from the completion of chemotherapy to lipid measurement in the treated group was 50 months (range, 2 to 138 months). The median total dose of cisplatin given was 720 mg (range, 300 to 1,625 mg). RESULTS: Mean total plasma cholesterol concentrations in the cisplatin group (5.87 mol/L) and the control group (5.70 mmol/L) did not differ significantly (P > .4). There was no significant difference for any of the variables between the chemotherapy and control groups and those of the New Zealand male population. There was a trend toward higher mean triglyceride concentrations in the chemotherapy group, but this did not reach significance. CONCLUSIONS: We have not demonstrated an elevation in total plasma cholesterol after cisplatin chemotherapy as has been reported by previous investigators. Our results suggest that in these patients, cisplatin-containing combination chemotherapy is not associated with a significant adverse effect on plasma lipid profile.     

Severe hypocholesterolaemia is often neglected in haematological malignancies

Aim of the studyIt is generally believed that high levels of cholesterol (hypercholesterolaemia) are life-threatening, while low levels seem to be positive. Unfortunately this assumption is far from true, and can be indicative of an underlying serious medical condition in most of the cases (i.e. cancer). However, the biological role of severe hypocholesterolaemia is poorly understood. Here, the possible biological process is being investigated. Cholesterol plays a key role in cell proliferation, hence it has been suggested that low cholesterol levels are probably linked to the high cellular cholesterol demands from neoplastic cells.Summary of the methodsWe used serum and isolated T-lymphocytes from patients with acute lymphoblast leukaemia and human lymphoblast cell line to test this hypothesis.ResultsWe found that patients with low serum cholesterol levels have instead high levels of cholesterol in lymphocytes. These data were supported with in vitro studies. In fact we have demonstrated that low cholesterol level in the culture medium was related to the neoplastic cellular growth, suggesting a greater use by lymphoma cells for their proliferation. Therefore by inhibiting cholesterol synthesis by mevastatin, in vitro, we showed that cholesterol levels did not change significantly in culture medium and the cellular growth was inhibited.Concluding statementFollowing these preliminary results, blood cholesterol levels could be potentially considered a good biological marker to follow up the neoplastic process.     

Perturbations of triglycerides but not of cholesterol metabolism are prevented by anti-tumour necrosis factor treatment in rats bearing an ascites hepatoma (Yoshida AH-130).

Rats transplanted with the ascites hepatoma Yoshida AH-130 developed a severely progressive cachexia, characterised by marked alterations in protein and lipid metabolism. In particular, high levels of serum triglycerides and free fatty acids were associated with altered levels and distribution of plasma cholesterol, with increased total and very low-density lipoprotein-low-density lipoprotein (VLDL-LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol. The tumour cells showed high rates of cholesterol synthesis and elevated content of free and esterified cholesterol, whereas total cholesterol synthesis was reduced in the host liver. To determine whether these perturbations could be related to the elevation of tumour necrosis factor alpha (TNF-alpha) previously shown in the AH-130 bearers (Tessitore L, Costelli P, Baccino FM 1993, Br J Cancer, 67, 15-23), either anti-TNF polyclonal antibodies or non-immune IgGs were injected daily after tumour transplantation. The anti-TNF treatment neither affected tumour growth nor prevented the serum cholesterol changes, while attenuating the hypertriglyceridaemia and the elevated serum free fatty acid levels. These data indicate that TNF does not appear to be directly involved in the altered cholesterol metabolism in AH-130 hosts, thus supporting the view that cholesterol metabolism and lipid metabolism are regulated differently during tumour growth.     

The role of diet history and biologic assays in the study of "diet and breast cancer"

Nutritional factors related to breast cancer were investigated by means of a hospital-based case-control study in Milan (Italy) and Montpellier (France). Liposoluble vitamins, cholesterol and triglycerides were measured in blood samples taken from interviewed subjects (319 cases and 344 controls). In addition serum zinc and copper was assessed in the Italian samples and serum fatty acids and malonyl-di-aldehyde in the French samples. A significant difference was found between cases and controls in total fat and cholesterol intake in both populations, and in saturated fatty acid and mono-unsaturated fatty acid consumption in the French samples. No difference emerged in liposoluble vitamin consumption in both populations nor in zinc and copper consumption in the Italian samples. A statistically significant higher serum level of cholesterol and plasma level of vitamin E was observed in cases compared to controls in both populations. The difference in plasma vitamin E was confirmed after adjustment on total cholesterol and triglycerides. Similarly, zinc serum level was higher in Italian cases than in Italian controls, while malonyl-di-aldehyde was lower in French cases than French controls. A multivariate analysis was performed after classification of cases and controls according to quantile distribution of controls. Nutrient consumption and relevant blood markers were directly or partially correlated in both populations. All known risk factors plus age, serum total cholesterol and triglycerides were used as covariates. The odds ratio values for the highest quantiles are: Dietary cholesterol, OR = 1.9 (1.1-3.4); total dietary lipids, OR = 1.9 (1.0-3.4); plasma vitamin E, OR = 4.2 (1.9-9.0); serum zinc, OR = 12.2 (5.4-27.7); serum malonyl-di-aldehyde, OR = 0.56 (0.33-0.97).     

Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study

We studied the relation of total serum cholesterol to all cancer and site-specific cancer incidence in a cohort based on a probability sample of the United States population. A total of 5125 men (yielding 459 cancers) and 7363 women (398 cancers) were initially examined in 1971-75 and followed a median of 10 yr. An examination of age-adjusted incidence rates by cholesterol level showed an inverse association between cholesterol and all cancer; lung, colorectal, pancreatic, and bladder cancers; and leukemia. In women a weak inverse relation (reflecting an elevated rate among those only in the lowest cholesterol quintile) was apparent for all cancer; more prominent inverse associations were seen for cancers of the lung, pancreas, bladder, cervix, and for leukemia. A more detailed analysis of cholesterol and colorectal cancer revealed little association in both men and women. For an aggregate group of smoking-related cancers, the inverse relation was especially prominent: the multivariate relative risk estimates for subjects in the lowest cholesterol quintile, compared to those in the highest quintile, were 2.1 (1.1-3.8) and 3.3 (1.4-7.8) for men and women, respectively. The inverse association was present for smoking-related cancers diagnosed 6 or more yr after cholesterol determination in both men and women, suggesting that this association cannot be simply dismissed as a preclinical cancer effect. Further investigation of the cholesterol-cancer question, particularly the relation between cholesterol and smoking-related cancers, may provide useful etiological leads.     

Are the effects of tamoxifen on the serum lipid profile modified by apolipoprotein E phenotypes?

BACKGROUND: Tamoxifen has favorable effects on the serum lipid profile. It has been suggested that the apolipoprotein (Apo) E phenotype can influence serum lipid parameters; the ApoE allele 4 (ApoE4) is associated with higher total and low-density lipoprotein (LDL) cholesterol levels. The ApoE phenotype also affects lipid responses to diets or treatment with statins. However, the effect of tamoxifen on the lipid profile in different ApoE phenotypes is unknown. PATIENTS AND METHODS: In the present study, we evaluated the effects of tamoxifen on the serum lipid profile in 11 ApoE4-positive postmenopausal women with breast cancer (phenotypes 3/4 and 4/4) compared with 33 ApoE4-negative women (phenotypes 3/2 and 3/3). Serum lipid parameters [high-density (HDL), LDL and total cholesterol, triglycerides, ApoAI, ApoB and lipoprotein (a)] were measured after an overnight fast before treatment and after 3 and 12 months. ApoE isoforms were determined by isoelectric focusing of delipidated very-low-density lipoproteins (VLDL). RESULTS: During the follow-up period, serum levels of total and LDL cholesterol and ApoB decreased significantly in both groups, but no significant differences were found. Concentrations of serum HDL cholesterol were not significantly different between both groups. However, serum ApoAI levels increased significantly in ApoE4-negative subjects (p = 0.00005), but no significant changes in ApoE4-positive women were observed. Serum triglyceride levels increased by 23.2% (p < 0.05) in ApoE4-positive patients, but they did not change significantly in ApoE4-negative patients. The LDL/HDL cholesterol ratio decreased similarly in the two groups, but the ApoAI/ApoB ratio, which may be a better predictor of cardiovascular events, significantly changed in the ApoE4-negative subjects. Finally, the median level of Lp(a) decreased by 43.4% in the ApoE4-negative patients, whereas it did not change significantly in the ApoE4-positive group. CONCLUSION: In postmenopausal Greek women with breast cancer, the levels of Lp(a) and triglycerides and the ApoAI/ApoB ratio respond more favorably to tamoxifen treatment in ApoE4-negative than in ApoE4-positive patients.