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. 2018 Jun 1;29(6):1468-1475.
doi: 10.1093/annonc/mdy104.

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)

D C Muller  1 , A M Hodge  2 , A Fanidi  3 , D Albanes  4 , X M Mai  5 , X O Shu  6 , S J Weinstein  4 , T L Larose  7 , X Zhang  8 , J Han  9 , M J Stampfer  10 , S A Smith-Warner  11 , J Ma  8 , J M Gaziano  12 , H D Sesso  13 , V L Stevens  14 , M L McCullough  14 , T M Layne  4 , R Prentice  15 , M Pettinger  15 , C A Thomson  16 , W Zheng  6 , Y T Gao  17 , N Rothman  4 , Y B Xiang  18 , H Cai  19 , R Wang  20 , J M Yuan  21 , W P Koh  22 , L M Butler  23 , Q Cai  19 , W J Blot  19 , J Wu  19 , P M Ueland  24 , Ø Midttun  25 , A Langhammer  26 , K Hveem  27 , M Johansson  28 , J Hultdin  29 , K Grankvist  29 , A A Arslan  30 , L Le Marchand  31 , G Severi  32 , M Johansson  33 , P Brennan  34
Affiliations

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)

D C Muller et al. Ann Oncol. .

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 prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3).

Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five 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 (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables.

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% CI: 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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Figures

Figure 1.
Figure 1.
Circulating log 25(OH)D as a function of day-of-year of blood draw. Scattered points are the observed concentrations, and the lines are the predicted cohort-specific mean concentrations given the calendar day on which blood was drawn. Predictions were made by regressing log 25(OH)D concentrations on sine and cosine functions of calendar day. A hierarchical model was used to allow the model coefficients to vary between cohorts.
Figure 2.
Figure 2.
Season-adjusted log 25(OH)D versus observed concentrations. Adjusted log 25(OH)D was calculated by subtracting the seasonal component of the model predicted concentration from the observed concentration. The gradient of color varies with the magnitude of the adjustment. This adjustment ranged from a subtraction of over 0.2 log-units (for those with blood drawn during the height of summer, magenta points) to an addition of over 0.2 log-units (for those with blood drawn in the middle of winter, dark blue (online) points).
Figure 3.
Figure 3.
Odds ratios for a doubling in 25(OH)D concentration overall, and by demographic and individual characteristics. Estimates are from conditional logistic regression models conditioned on matched case set, and adjusted for four categories of circulating cotinine. P-values are from likelihood ratio tests of the interaction terms between 25(OH)D and each covariate.
Figure 4.
Figure 4.
Odds ratios for a doubling in 25(OH)D concentration separately for each cohort. Estimates are from a conditional logistic regression model conditioned on matched case set, and adjusted for four categories of circulating cotinine. The P-value is from likelihood ratio test of the interaction terms between 25(OH)D cohort.
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