结直肠癌诊断后维生素 D 状况与肿瘤免疫反应的患者生存
Vitamin D status after colorectal cancer diagnosis and patient survival according to immune response to tumour.
机构信息
Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology and Biostatistics, The Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Hubei, PR China.
出版信息
Eur J Cancer. 2018 Nov;103:98-107. doi: 10.1016/j.ejca.2018.07.130. Epub 2018 Sep 13.
BACKGROUND
High-level plasma 25-hydroxyvitamin D [25(OH)D] has been associated with lower colorectal cancer incidence and mortality. Considering evidence indicating immunomodulatory effects of vitamin D, we hypothesised that survival benefits from high systemic vitamin D level might be stronger for colorectal carcinoma with lower immune response to tumour.
METHODS
Using 869 colon and rectal cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study, we assessed the prognostic association of postdiagnosis 25(OH)D score [derived from diet and lifestyle variables to predict plasma 25(OH)D level] in strata of levels of histopathologic lymphocytic reaction. The Cox proportional hazards regression model was adjusted for potential confounders, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, PTGS2 (cyclooxygenase-2) expression and KRAS, BRAF and PIK3CA mutations.
RESULTS
The association of postdiagnosis 25(OH)D score with colorectal cancer-specific mortality differed by levels of peritumoural lymphocytic reaction (p = 0.001). Multivariable-adjusted mortality hazard ratios for a quintile-unit increase of 25(OH)D score were 0.69 [95% confidence interval (CI), 0.54-0.89] in cases with negative/low peritumoural lymphocytic reaction, 1.08 (95% CI, 0.93-1.26) in cases with intermediate peritumoural reaction and 1.25 (95% CI, 0.75-2.09) in cases with high peritumoural reaction. The survival association of the 25(OH)D score did not significantly differ by Crohn's-like lymphoid reaction, intratumoural periglandular reaction or tumour-infiltrating lymphocytes.
CONCLUSIONS
The association between the 25(OH)D score and colorectal cancer survival is stronger for carcinomas with lower peritumoural lymphocytic reaction. Our results suggesting interactive effects of vitamin D and immune response may contribute to personalised dietary and lifestyle intervention strategies.
背景
高水平的血浆 25-羟维生素 D [25（OH）D] 与较低的结直肠癌发病率和死亡率相关。考虑到维生素 D 具有免疫调节作用的证据，我们假设对于对肿瘤免疫反应较低的结直肠癌，高全身性维生素 D 水平带来的生存益处可能更强。
方法
利用护士健康研究和健康专业人员随访研究中的 869 例结肠癌和直肠癌病例，我们评估了诊断后 25（OH）D 评分（通过饮食和生活方式变量预测血浆 25（OH）D 水平）与组织病理学淋巴细胞反应水平分层之间的预后相关性。Cox 比例风险回归模型调整了潜在的混杂因素，包括微卫星不稳定性、CpG 岛甲基化表型、LINE-1 甲基化、PTGS2（环氧化酶-2）表达和 KRAS、BRAF 和 PIK3CA 突变。
结果
诊断后 25（OH）D 评分与结直肠癌特异性死亡率的相关性因肿瘤周围淋巴细胞反应水平而异（p=0.001）。多变量调整后的死亡率风险比为，25（OH）D 评分每增加一个五分位数单位，肿瘤周围淋巴细胞反应阴性/低的病例为 0.69（95%置信区间，0.54-0.89），肿瘤周围反应中等的病例为 1.08（95%置信区间，0.93-1.26），肿瘤周围反应高的病例为 1.25（95%置信区间，0.75-2.09）。25（OH）D 评分与结直肠癌的生存关联在 Crohn 样淋巴反应、肿瘤内腺体周围反应或肿瘤浸润淋巴细胞方面没有显著差异。
结论
25（OH）D 评分与结直肠癌生存之间的相关性在肿瘤周围淋巴细胞反应较低的癌中更强。我们的研究结果表明，维生素 D 与免疫反应之间的相互作用可能有助于制定个性化的饮食和生活方式干预策略。
Zotero 插件