No association between circulating concentrations of vitamin D and risk of lung cancer: An analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3)

Abstract

Background

There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in pre-diagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3).

Patients and methods

The study included 5,313 lung cancer cases and 5,313 controls selected from. Blood samples for the cases were collected, on average, 5 years prior to lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in 5 categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D₂ (25(OH)D₂) and 25-hydroxyvitamin D₃ (25(OH)D₃) and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for 25(OH)D as both a continuous and categorical variable.

Results

Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% confidence interval: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology.

Conclusion

This study did not support an association between vitamin D concentrations and lung cancer risk.

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Significance: We found that a distinct and abundant microbiome drives suppressive monocytic cellular differentiation in pancreatic cancer via selective Toll-like receptor ligation leading to T-cell anergy. Targeting the microbiome protects against oncogenesis, reverses intratumoral immune tolerance, and enables efficacy for checkpoint-based immunotherapy. These data have implications for understanding immune suppression in pancreatic cancer and its reversal in the clinic. Cancer Discov; 8(4); 403–16. ©2018 AACR.

See related commentary by Riquelme et al., p. 386.

This article is highlighted in the In This Issue feature, p. 371

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