以前对脂肪酸和乳腺癌风险的研究显示出不同的结果,这可能部分是由于肿瘤异质性。先前的研究还表明了特定脂肪酸在免疫调节中的重要作用,T细胞功能,和炎症,这表明特定脂肪酸对乳腺癌风险的影响可能因免疫炎症标志物的肿瘤表达而异。因此,我们旨在通过肿瘤组织中免疫炎症标志物(CD4,CD8,CD20,CD163,COX-2)和脂肪酸合酶(FAS)的表达来评估诊断前红细胞膜脂肪酸与乳腺癌风险之间的关系。
我们在护士健康研究II中进行了匹配的病例对照研究(n=235例病例和235例对照)。从1996年至1999年收集血液样本。收集肿瘤组织块,用于血液收集后诊断的病例,直到2006年。根据匹配因素和潜在混杂因素调整后的无条件名义多因素logistic回归用于评估脂肪酸和乳腺癌风险之间的关联是否因肿瘤表达亚型而异。通过免疫组织化学确定。使用非条件逻辑回归通过肿瘤表达亚型分别估计赔率比(OR)和95%置信区间(CI)。
脂肪酸与乳腺癌风险之间的关联在肿瘤CD4、CD20、CD163或COX-2之间没有显著差异。然而,n-3多不饱和脂肪酸(PUFAs)与CD8low而不是CD8high癌症呈负相关(CD8lowORT3vsT1=0.45,95%CI0.23-0.87,Ptrend=0.02;CD8highORT3vsT1=1.19,95%CI0.62-2.26,Ptrend=0.62;Phet=0.04)。n-6PUFA与CD8high而不是CD8low癌症呈负相关(CD8highORT3vsT1=0.61,95%CI0.32-1.14,Ptrend=0.11;CD8lowORT3vsT1=1.63,95%CI0.87-3.04,Ptrend=0.12;Phet=0.02)。反式脂肪酸与FAShigh肿瘤呈正相关,但与FASlow肿瘤无关(FAShighORT3vsT1=2.94,95%CI1.46-5.91,Ptrend=0.002;FASlowORT3vsT1=0.99,95%CI0.52-1.92,Ptrend=0.97;Phet=0.01)。
结果表明,n-3PUFA的作用,n-6PUFA,和反式脂肪酸对乳腺癌的风险可能因肿瘤组织表达亚型而异。研究结果表明潜在的免疫调节和FAS介导的机制。
Previous studies of fatty acids and breast cancer risk have shown mixed results, which may be due in part to tumor heterogeneity. Prior research has also illustrated an important role of specific fatty acids in immune regulation, T cell function, and inflammation, indicating that the effects of specific fatty acids on breast cancer risk may vary by tumor expression of immuno-inflammatory markers. We therefore aimed to evaluate the relationships between prediagnostic erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers (CD4, CD8, CD20, CD163, COX-2) and fatty acid synthase (FAS).
We conducted a matched
case-control study nested within the Nurses\' Health Study II (n = 235 cases and 235 controls). Blood samples were collected from 1996 to 1999. Tumor tissue blocks were collected for cases diagnosed after blood collection and through 2006. Unconditional nominal polytomous logistic regression adjusted for matching factors and potential confounders was used to assess whether associations between fatty acids and breast cancer risk varied by tumor expression subtype, ascertained via immunohistochemistry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated separately by tumor expression subtype using unconditional logistic regression.
Associations between fatty acids and breast cancer risk did not vary substantially by tumor CD4, CD20, CD163, or COX-2. However, n-3 polyunsaturated fatty acids (PUFAs) were inversely associated with CD8low but not CD8high cancers (CD8low ORT3 vs T1 = 0.45, 95% CI 0.23-0.87, Ptrend = 0.02; CD8high ORT3 vs T1 = 1.19, 95% CI 0.62-2.26, Ptrend = 0.62; Phet = 0.04). n-6 PUFAs were suggestively inversely associated with CD8high but not CD8low cancers (CD8high ORT3 vs T1 = 0.61, 95% CI 0.32-1.14, Ptrend = 0.11; CD8low ORT3 vs T1 = 1.63, 95% CI 0.87-3.04, Ptrend = 0.12; Phet = 0.02). Trans fatty acids were positively associated with FAShigh but not FASlow tumors (FAShigh ORT3 vs T1 = 2.94, 95% CI 1.46-5.91, Ptrend = 0.002; FASlow ORT3 vs T1 = 0.99, 95% CI 0.52-1.92, Ptrend = 0.97; Phet = 0.01).
Results indicate that the effects of n-3 PUFAs, n-6 PUFAs, and trans fatty acids on breast cancer risk may vary by tumor tissue expression subtypes. Findings suggest potential immuno-modulatory and FAS-mediated mechanisms.