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芬兰吸烟者血清植烷酸和降植烷酸水平与前列腺癌风险

Serum phytanic and pristanic acid levels and prostate cancer risk in Finnish smokers.

作者信息

Wright Margaret E, Albanes Demetrius, Moser Ann B, Weinstein Stephanie J, Snyder Kirk, Männistö Satu, Gann Peter H

机构信息

Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois; American Academy of Pediatrics, Elk Grove Village, Illinois.

出版信息

Cancer Med. 2014 Dec;3(6):1562-9. doi: 10.1002/cam4.319. Epub 2014 Aug 16.

Abstract

Phytanic acid is a saturated branched-chain fatty acid found predominantly in red meat and dairy products, and may contribute to the elevated risks of prostate cancer associated with higher consumption of these foods. Pristanic acid is formed during peroxisomal oxidation of phytanic acid, and is the direct substrate of α-Methyl-CoA-Racemase (AMACR)--an enzyme that is consistently overexpressed in prostate tumors relative to benign tissue. We measured phytanic and pristanic acids as percentages of total fatty acids by gas chromatography-mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases and 300 matched controls, all of whom were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study supplementation trial and follow-up cohort. In addition to providing a fasting blood sample at baseline, all men completed extensive diet, lifestyle, and medical history questionnaires. Among controls, the strongest dietary correlates of serum phytanic and pristanic acids were saturated fat, dairy fat, and butter (r = 0.50 and 0.40, 0.46 and 0.38, and 0.40 and 0.37, respectively; all P-values <0.001). There was no association between serum phytanic acid and risk of total or aggressive prostate cancer in multivariate logistic regression models (for increasing quartiles, odds ratios (OR) and 95% confidence intervals (CI) for aggressive cancer were 1.0 (referent), 1.62 (0.97-2.68), 1.12 (0.66-1.90), and 1.14 (0.67-1.94), P(trend) = 0.87). Pristanic acid was strongly correlated with phytanic acid levels (r = 0.73, P < 0.0001), and was similarly unrelated to prostate cancer risk. Significant interactions between phytanic and pristanic acids and baseline circulating β-carotene concentrations were noted in relation to total and aggressive disease among participants who did not receive β-carotene supplements as part of the original ATBC intervention trial. In summary, we observed no overall association between serum phytanic and pristanic acid levels and prostate cancer risk. Findings indicating that the direction and magnitude of these associations depended upon serum levels of the antioxidant β-carotene among men not taking β-carotene supplements should be interpreted cautiously, as they are likely due to chance.

摘要

植烷酸是一种饱和支链脂肪酸,主要存在于红肉和乳制品中,可能会增加因大量食用这些食物而患前列腺癌的风险。降植烷酸是植烷酸在过氧化物酶体氧化过程中形成的,是α-甲基辅酶A消旋酶(AMACR)的直接底物,相对于良性组织,该酶在前列腺肿瘤中一直呈过表达状态。我们采用气相色谱-质谱联用技术,测定了300例前列腺癌病例和300例匹配对照的诊断前血液样本中植烷酸和降植烷酸占总脂肪酸的百分比,所有这些人均为α-生育酚、β-胡萝卜素癌症预防(ATBC)研究补充试验及随访队列的参与者。除了在基线时提供空腹血样外,所有男性还完成了详细的饮食、生活方式和病史问卷。在对照组中,血清植烷酸和降植烷酸与饮食的最强相关性在于饱和脂肪、乳脂肪和黄油(r分别为0.50和0.40、0.46和0.38、0.40和0.37;所有P值均<0.001)。在多因素逻辑回归模型中,血清植烷酸与前列腺癌总体或侵袭性癌症风险之间无关联(对于四分位数增加,侵袭性癌症的比值比(OR)和95%置信区间(CI)分别为1.0(参照值)、1.62(0.97 - 2.68)、1.12(0.66 - 1.90)和1.14(0.67 - 1.94),P趋势 = 0.87)。降植烷酸与植烷酸水平高度相关(r = 0.73,P < 0.0001),并且同样与前列腺癌风险无关。在未接受作为原始ATBC干预试验一部分的β-胡萝卜素补充剂的参与者中,发现植烷酸和降植烷酸与基线循环β-胡萝卜素浓度之间在总体和侵袭性疾病方面存在显著相互作用。总之,我们观察到血清植烷酸和降植烷酸水平与前列腺癌风险之间无总体关联。表明这些关联的方向和程度取决于未服用β-胡萝卜素补充剂男性的抗氧化剂β-胡萝卜素血清水平的研究结果应谨慎解读,因为它们可能是偶然因素导致的。

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