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Pancreatic Cancer causes include smoking and low vitamin D, adding vitamin D might help – Jan 2017

Pancreatic Cancer Survival: Plasma Levels of 25-Hydroxyvitamin D and Smoking

Journal of Clinical Oncology - before print Jan 17, 2017, DOI: 10.1200/JCO.2016.69.4364
Alain Braillon braillon.alain at gmail.com.

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To the Editor:

Yuan et al1 observed longer survival in patients with pancreatic cancer who had sufficient prediagnostic plasma levels of 25-hydroxyvitamin D (25[OH]D) and suggest that agonists of the vitamin D receptor are a potentially therapeutic approach. However, the limitations of their study warrant comment.

  • First, the cohort mainly consisted of women (76% in the group with insufficient 25[OH]D), whereas the incidence of pancreatic cancer was 50% higher in men than in women.2
  • Second, the shape of the overall survival curve, when the number of cases was significant, raises questions about (1) the clinical relevance of the findings, because the difference in survival between sufficient and insufficient 25(OH)D is less than 2 months; and (2) the causality, because the difference in survival is almost constant (see Fig 1 in Yuan et al1).
  • Third, using cut points to derive subgroups is not appropriate when there is a continuous distribution of the values with no obvious modal values.

This not only concerns the three groups for 25(OH)D but mainly the confounding factors. Indeed, for smoking, the main cause of pancreatic cancer, Yuan et al1 only assessed it as never, past, or current. Adjustment is always a complex issue; however, here it may be even more a catch 22 because

  • (1) smokers have lower 25(OH)D levels3 and
  • (2) lower plasma 25(OH)D levels are associated with a higher risk of tobacco-related cancers.4

Last, a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort failed to show evidence that 25(OH)D plays a protective role in pancreatic cancer.5 In the general population, association between the lowest 25(OH)D quartile and cancer-specific mortality is not nonsignificant and disappears after adjustment.6


  • 1. Yuan C, Qian ZR, Babic A, et al: Prediagnostic plasma 25-hydroxyvitamin D and pancreatic cancer survival. J Clin Oncol 34:2899-2905, 2016 Link
  • 2. Hruban RH, Hiraoka N, Iacobuzio-Donahue C, et al: Ductal adenocarcinoma of the pancreas, in Bosman FTJ, Lakhani SR, Ohgaki H (eds): WHO Classification of Tumours of the Digestive System (ed 4). Lyon, France, International Agency for Research on Cancer, 2010, pp 281-291
  • 3. Tønnesen R, Hovind PH, Jensen LT, et al: Determinants of vitamin D status in young adults: Influence of lifestyle, sociodemographic and anthropometric factors. BMC Public Health 16:385, 2016 CrossRef, Medline
  • 4. Afzal S, Bojesen SE, Nordestgaard BG: Low plasma 25-hydroxyvitamin D and risk of tobacco-related cancer. Clin Chem 59:771-780, 2013 CrossRef, Medline
  • 5. Piper MR, Freedman DM, Robien K, et al: Vitamin D-binding protein and pancreatic cancer: A nested case-control study. Am J Clin Nutr 101:1206-1215, 2015 CrossRef, Medline
  • 6. Melamed ML, Michos ED, Post W, et al: 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 168:1629-1637, 2008 CrossRef, Medline