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血清胆固醇与前列腺癌风险:芬兰前列腺癌筛查随机研究

Serum cholesterol and prostate cancer risk in the Finnish randomized study of screening for prostate cancer.

机构信息

Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Department of Urology, Tampere University Hospital, Tampere, Finland.

出版信息

Prostate Cancer Prostatic Dis. 2019 Mar;22(1):66-76. doi: 10.1038/s41391-018-0087-0. Epub 2018 Sep 13.

Abstract

BACKGROUND

Hypercholesterolemia has been associated with advanced stage prostate cancer (PCa), but the role of lipid parameters such as HDL and triglycerides is unclear. We examined PCa risk by lipid parameters in a population nested within the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC).

METHODS

Cholesterol measurements were available on 17,696 men. During the 17-year median follow-up, 2404 PCa cases were diagnosed. Cox regression model was used to estimate hazard ratios (HR) and their 95% confidence intervals (95% CI) for overall PCa risk and stratified by Gleason grade and tumor stage. We compared normolipidemic and hyperlipidemic men on four cholesterol parameters total cholesterol (TC), HDL, LDL, and triglycerides (TG), analyzed as time-dependent variables.

RESULTS

TC in the highest tertile (above 5.1 mmol/l) and LDL above 3 mmol/l were associated with increased risk of Gleason 8-10 cancer (HR 1.42, 95% CI 1.04-1.95 and HR 1.38, 95% CI 1.02-1.86, respectively). Further, overall PCa risk was elevated in the 3-year lag time analysis by TC in the highest two tertiles (HR 1.27, 95% CI 1.05-1.54 for TC above 4.4 mmol/l, and HR 1.26, 95% CI 1.05-1.51 for TC above 5.1 mmol/l) and HDL in the highest tertile (HR 1.33, 95% CI 1.08-1.64) and above 1 mmol/l (HR 1.29, 95% CI 1.01-1.65). In contrast, TC in the highest tertile was associated with a decreased risk of PCa with 20-year lag time. The risk associations for overall PCa grew stronger with added lag time but were observed only in the FinRSPC control arm. Statin use did not modify the risk association.

CONCLUSIONS

Hypercholesterolemia may increase overall PCa risk in short-term, inverse risk association was observed with 20-years' time lag. Similar risk increase of overall PCa was also observed for elevated HDL, conflicting with previous findings on the subject.

摘要

背景

高胆固醇血症与晚期前列腺癌(PCa)有关,但高密度脂蛋白(HDL)和甘油三酯等血脂参数的作用尚不清楚。我们在芬兰前列腺癌筛查随机研究(FinRSPC)的人群中,通过血脂参数检查了 PCa 风险。

方法

共纳入 17696 名男性,检测了胆固醇水平。中位随访 17 年期间,诊断出 2404 例 PCa 病例。使用 Cox 回归模型估计总胆固醇(TC)、HDL、LDL 和甘油三酯(TG)四个胆固醇参数的总体 PCa 风险的危险比(HR)及其 95%置信区间(95%CI),并按 Gleason 分级和肿瘤分期进行分层。我们将正常脂质血症和脂质血症男性按 TC、HDL、LDL 和 TG 四个胆固醇参数进行比较,分析为时间依赖性变量。

结果

TC 最高三分位数(>5.1mmol/L)和 LDL 高于 3mmol/L 与 Gleason 8-10 癌症风险增加相关(HR 1.42,95%CI 1.04-1.95 和 HR 1.38,95%CI 1.02-1.86)。进一步,在 TC 最高两个三分位数(TC 高于 4.4mmol/L,HR 1.27,95%CI 1.05-1.54;TC 高于 5.1mmol/L,HR 1.26,95%CI 1.05-1.51)和 HDL 最高三分位数(HR 1.33,95%CI 1.08-1.64)和高于 1mmol/L(HR 1.29,95%CI 1.01-1.65)时,3 年滞后时间分析中总体 PCa 风险升高。相反,TC 最高三分位数与 20 年滞后时间的 PCa 风险降低相关。随着滞后时间的增加,总体 PCa 的风险相关性增强,但仅在 FinRSPC 对照组中观察到。他汀类药物的使用并没有改变风险相关性。

结论

高胆固醇血症可能会增加短期的总体 PCa 风险,而与 20 年时滞相关的风险呈反比。同样,升高的 HDL 也观察到了总体 PCa 的风险增加,这与之前关于该主题的研究结果相矛盾。

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