Yuan Chen, Qian Zhi Rong, Babic Ana, Morales-Oyarvide Vicente, Rubinson Douglas A, Kraft Peter, Ng Kimmie, Bao Ying, Giovannucci Edward L, Ogino Shuji, Stampfer Meir J, Gaziano John Michael, Sesso Howard D, Buring Julie E, Cochrane Barbara B, Chlebowski Rowan T, Snetselaar Linda G, Manson JoAnn E, Fuchs Charles S, Wolpin Brian M
Chen Yuan, Zhi Rong Qian, Ana Babic, Vicente Morales-Oyarvide, Douglas A. Rubinson, Kimmie Ng, Shuji Ogino, Charles S. Fuchs, and Brian M. Wolpin, Dana-Farber Cancer Institute and Harvard Medical School; Peter Kraft, Edward L. Giovannucci, Shuji Ogino, Meir J. Stampfer, Howard D. Sesso, Julie E. Buring, and JoAnn E. Manson, Harvard School of Public Health; Ying Bao, Edward L. Giovannucci, Shuji Ogino, Meir J. Stampfer, John Michael Gaziano, Howard D. Sesso, JoAnn E. Manson, and Charles S. Fuchs, Brigham and Women's Hospital and Harvard Medical School; John Michael Gaziano, Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA; Barbara B. Cochrane, University of Washington School of Nursing, Seattle, WA; Rowan T. Chlebowski, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA; and Linda G. Snetselaar, University of Iowa College of Public Health, Iowa City, IA.
J Clin Oncol. 2016 Aug 20;34(24):2899-905. doi: 10.1200/JCO.2015.66.3005. Epub 2016 Jun 20.
Although vitamin D inhibits pancreatic cancer proliferation in laboratory models, the association of plasma 25-hydroxyvitamin D [25(OH)D] with patient survival is largely unexplored.
We analyzed survival among 493 patients from five prospective US cohorts who were diagnosed with pancreatic cancer from 1984 to 2008. We estimated hazard ratios (HRs) for death by plasma level of 25(OH)D (insufficient, < 20 ng/mL; relative insufficiency, 20 to < 30 ng/mL; sufficient ≥ 30 ng/mL) by using Cox proportional hazards regression models adjusted for age, cohort, race and ethnicity, smoking, diagnosis year, stage, and blood collection month. We also evaluated 30 tagging single-nucleotide polymorphisms in the vitamin D receptor gene, requiring P < .002 (0.05 divided by 30 genotyped variants) for statistical significance.
Mean prediagnostic plasma level of 25(OH)D was 24.6 ng/mL, and 165 patients (33%) were vitamin D insufficient. Compared with patients with insufficient levels, multivariable-adjusted HRs for death were 0.79 (95% CI, 0.48 to 1.29) for patients with relative insufficiency and 0.66 (95% CI, 0.49 to 0.90) for patients with sufficient levels (P trend = .01). These results were unchanged after further adjustment for body mass index and history of diabetes (P trend = .02). The association was strongest among patients with blood collected within 5 years of diagnosis, with an HR of 0.58 (95% CI, 0.35 to 0.98) comparing patients with sufficient to patients with insufficient 25(OH)D levels. No single-nucleotide polymorphism at the vitamin D receptor gene met our corrected significance threshold of P < .002; rs7299460 was most strongly associated with survival (HR per minor allele, 0.80; 95% CI, 0.68 to 0.95; P = .01).
We observed longer overall survival in patients with pancreatic cancer who had sufficient prediagnostic plasma levels of 25(OH)D.
尽管在实验室模型中维生素D可抑制胰腺癌的增殖，但血浆25-羟基维生素D[25(OH)D]与患者生存率之间的关联在很大程度上尚未得到探索。
我们分析了来自美国五个前瞻性队列的493例胰腺癌患者的生存情况，这些患者于1984年至2008年被诊断为胰腺癌。我们通过Cox比例风险回归模型，对年龄、队列、种族和民族、吸烟、诊断年份、分期和采血月份进行调整，估计了根据血浆25(OH)D水平（不足，<20 ng/mL；相对不足，20至<30 ng/mL；充足，≥30 ng/mL）得出的死亡风险比（HR）。我们还评估了维生素D受体基因中的30个标签单核苷酸多态性，要求P<0.002（0.05除以30个基因分型变体）才有统计学意义。
诊断前血浆25(OH)D的平均水平为24.6 ng/mL，165例患者（33%）维生素D不足。与水平不足的患者相比，相对不足的患者经多变量调整后的死亡HR为0.79（95%CI，0.48至1.29），充足的患者为0.66（95%CI，0.49至0.90）（P趋势=0.01）。在进一步调整体重指数和糖尿病史后，这些结果未改变（P趋势=0.02）。在诊断后5年内采血的患者中，这种关联最为明显，充足的25(OH)D水平患者与不足患者相比，HR为0.58（95%CI,0.35至0.98）。维生素D受体基因中没有单核苷酸多态性达到我们校正后的P<0.002的显著性阈值；rs7299460与生存率的关联最为强烈（每个次要等位基因的HR，0.80；95%CI，0.68至0.95；P=0.01）。
我们观察到诊断前血浆25(OH)D水平充足的胰腺癌患者总生存期更长。
