Katzke Verena Andrea, Sookthai Disorn, Johnson Theron, Kühn Tilman, Kaaks Rudolf
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
BMC Med. 2017 Dec 19;15(1):218. doi: 10.1186/s12916-017-0976-4.
Circulating concentrations of lipid biomarkers are associated with risk of cardiovascular diseases (CVD). The evidence for a relationship with cancer risk, however, is not entirely consistent. This study aims to assess the relationships of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein (a) (apo(a)), apoB-100, and lipoprotein(a) (Lp(a)) with risk of common cancer forms and total cancer mortality in comparison to incidence and mortality of CVD.
We selected a case-cohort sample out of the prospective EPIC-Heidelberg study, including a random subcohort (n = 2739), and cases of cancer (n = 1632), cancer mortality (n = 761), CVD (n = 1070), and CVD mortality (n = 381). Concentrations of lipid biomarkers were measured in pre-diagnostic blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Prentice-weighted Cox regression models.
High levels of circulating apoB-100 and TG were inversely associated and high HDL-C levels were positively associated with breast cancer risk (highest vs. lowest quartile (Q4 vs. Q1), HR 0.71, 95% CI 0.52-0.98; HR 0.65, 0.46-0.92; and HR 1.39, 1.01-1.93). Higher levels of Lp(a) were associated with an increase in prostate cancer risk (Q4 vs. Q1, HR 1.43, 1.02-2.03) and high levels of apo(a) were associated with a decrease in lung cancer risk (Q4 vs. Q1, HR 0.52, 0.30-0.91). High TC, HDL-C, apo(a), and Lp(a) levels were associated with a reduction in total cancer mortality (Q4 vs. Q1, HR 0.71, 0.54-0.94; HR 0.67, 0.50-0.91; HR 0.71, 0.54-0.93; and HR 0.74, 0.57-0.98). All lipid biomarkers were associated with risk of myocardial infarction, whereby TC, apoB-100, TG, and Lp(a) were positively and HLD-C and apo(a) inversely associated with risk. Only high levels of TG were associated with an increased risk of stroke. None of the lipids were associated with risk of colorectal cancer and with risk of CVD mortality after multivariable adjustments.
This prospective study demonstrates inverse associations of lipid biomarkers with cancer incidence and mortality, with the exception of positive associations of HDL-C and Lp(a) with breast and prostate cancer risk, respectively. Thus, the observed cancer risk pattern clearly differs from the CVD risk pattern.
循环中脂质生物标志物的浓度与心血管疾病（CVD）风险相关。然而，其与癌症风险之间关系的证据并不完全一致。本研究旨在评估总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、甘油三酯（TG）、载脂蛋白（a）（apo(a)）、载脂蛋白B-100（apoB-100）和脂蛋白(a)（Lp(a)）与常见癌症类型风险及总癌症死亡率之间的关系，并与CVD的发病率和死亡率进行比较。
我们从前瞻性的海德堡欧洲癌症与营养前瞻性调查（EPIC-Heidelberg）研究中选取了一个病例队列样本，包括一个随机子队列（n = 2739），以及癌症病例（n = 1632）、癌症死亡病例（n = 761）、CVD病例（n = 1070）和CVD死亡病例（n = 381）。在诊断前的血液样本中测量脂质生物标志物的浓度。使用Prentice加权Cox回归模型估计风险比（HR）和95%置信区间（CI）。
循环中高水平的apoB-100和TG与乳腺癌风险呈负相关，而高水平的HDL-C与乳腺癌风险呈正相关（最高四分位数与最低四分位数相比（Q4 vs. Q1），HR 0.71，95% CI 0.52 - 0.98；HR 0.65，0.46 - 0.92；以及HR 1.39，1.01 - 1.93）。较高水平的Lp(a)与前列腺癌风险增加相关（Q4 vs. Q1，HR 1.43，1.02 - 2.03），而高水平的apo(a)与肺癌风险降低相关（Q4 vs. Q1，HR 0.52，0.30 - 0.91）。高TC、HDL-C、apo(a)和Lp(a)水平与总癌症死亡率降低相关（Q4 vs. Q1，HR 0.71，0.54 - 0.94；HR 0.67，0.50 - 0.91；HR 0.71，0.54 - 0.93；以及HR 0.74，0.57 - 0.98）。所有脂质生物标志物均与心肌梗死风险相关，其中TC、apoB-100、TG和Lp(a)与风险呈正相关，而HDL-C和apo(a)与风险呈负相关。仅高水平的TG与中风风险增加相关。多变量调整后，没有一种脂质与结直肠癌风险及CVD死亡率风险相关。
这项前瞻性研究表明，脂质生物标志物与癌症发病率和死亡率呈负相关，但HDL-C和Lp(a)分别与乳腺癌和前列腺癌风险呈正相关除外。因此，观察到的癌症风险模式明显不同于CVD风险模式。
