Esophageal cancerVitamin D levels

There is one report of reduced risk of esophageal cancer with respect to oral intake of vitamin D:

Two case-control studies in Italy were examined for the relation between dietary vitamin D intake and squamous cell carcinoma of the esophagus (SCCE; 304 cases). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by multiple logistic regression analysis. The adjusted OR for SCCE was 0.58 (95% CI 0.39-0.86) for the highest tertile of vitamin D intake. Using a reference group of those in the highest tertile of vitamin D who were never/former smokers, ORs were 8.7 (95% CI 4.1-18.7) for SCCE among heavy smokers in the lowest vitamin D tertile; similarly, compared with those in the highest tertile of vitamin D who drank <3 alcoholic drinks/day, corresponding ORs were 41.9 (95% CI 13.7-128.6) for SCCE, among heavy alcohol drinkers in the lowest vitamin D tertile. The inverse associations between dietary vitamin D intake and risk of SCCE and, perhaps, oral/pharyngeal cancer, which were most pronounced among heavy current smokers and heavy consumers of alcohol1.

However, we did not find any papers reporting reduced risk of esophageal cancer with respect to prediagnostic serum 25(OH)D levels.

A study in China found an increased risk of esophageal cancer with higher serum 25(OH)D levels for men but not women2. That study was from Linxian, a semi-arid mountainous area in central China (36º N latitude), which has a mainly rural population with some of the highest rates of oesophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma in the world2. However, there are many nontraditional risk factors for esophageal cancer in China such as high sodium intake and human papilloma virus (HPV) infection3, so some of these factors could confound the vitamin D association.

A recent analysis of pooled case-control data of prediagnostic serum 25(OH)D found no trend or odds ratio (risk) for quintiles from <25 nmol/L to >100 nmol/L and no statistically significant variation from unity for any quintile4. One possible reason for the null finding mentioned in the paper was “short median follow-up in the Shanghai Men’s Health Study, a major contributor of the Asian subjects in the analysis, leaves open the possibility that occult cancers influenced vitamin D concentrations.” There is a long lag time between initiation and detection5. Another reason for the null finding may be that the controls were not carefully matched to the controls. Although controls were matched for blood collection within 30 days, this may not be sufficient. As shown in a study of seasonal variation of serum 25(OH)D level among those aged 45 years in the U.K., serum 25(OH)D levels increase from 35 nmol/L in winter to 75 nmol/L in summer, a rate of 7 nmol/L or 20% in winter and 10% in summer6. This change is enough to cause some changes in quantile, which were spaced by 25 nmol/L in the higher quantiles.

A third reason for the null finding could have been the long follow-up period between serum draw and end of follow-up. The periods ranged from 1.7 to 11.8 years. The authors stated that no effect of follow-up time was found. However, a review of breast cancer incidence rates with respect to follow-up time found no statistically significant correlations for breast cancer incidence with respect to serum 25(OH)D level after three years7.

Thus, there are enough reasons why Abnet et al4 might have unaccounted for confounding factors that it may not represent the actual relationship between serum 25(OH)D and esophageal cancer risk.

Page last edited: 22 August 2011


  1. Lipworth, L. Rossi, M. McLaughlin, J. K. Negri, E. Talamini, R. Levi, F. Franceschi, S. La Vecchia, C. Dietary vitamin D and cancers of the oral cavity and esophagus. Ann Oncol. 2009 Jun 1;
  2. Chen, W. Dawsey, S. M. Qiao, Y. L. Mark, S. D. Dong, Z. W. Taylor, P. R. Zhao, P. Abnet, C. C. Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers. Br J Cancer. 2007 Jul 2; 97 (1): 123-8.
  3. Zheng, S. Vuitton, L. Sheyhidin, I. Vuitton, D. A. Zhang, Y. Lu, X. Northwestern China: a place to learn more on oesophageal cancer. Part one: behavioural and environmental risk factors. Eur J Gastroenterol Hepatol. 2010 Aug; 22 (8): 917-25.
  4. Abnet, C. C. Chen, Y. Chow, W. H. Gao, Y. T. Helzlsouer, K. J. Le Marchand, L. McCullough, M. L. Shikany, J. M. Virtamo, J. Weinstein, S. J. Xiang, Y. B. Yu, K. Zheng, W. Albanes, D. Arslan, A. A. Campbell, D. S. Campbell, P. T. Hayes, R. B. Horst, R. L. Kolonel, L. N. Nomura, A. M. Purdue, M. P. Snyder, K. Shu, X. O. Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. 2010 Jul 1; 172 (1): 94-106.
  5. Gammon, M. D. Schoenberg, J. B. Ahsan, H. Risch, H. A. Vaughan, T. L. Chow, W. H. Rotterdam, H. West, A. B. Dubrow, R. Stanford, J. L. Mayne, S. T. Farrow, D. C. Niwa, S. Blot, W. J. Fraumeni, J. F., Jr. Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst. 1997 Sep 3; 89 (17): 1277-84.
  6. Hypponen, E. Power, C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007 Mar; 85 (3): 860-8.
  7. Grant, W. B. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines. Dermato-endocrinology. 2011; 3 (3):