Sir,
Vaughan-Shaw et al (2017) claimed that 25(OH)D concentration is associated with better cancer outcome, and the observed association of functional variants in vitamin D pathway genes with outcome supports a causal link. This deserves a comment.
First, using arbitrary cut-points to derive subgroups for 25(OH)D is not appropriate when there is a continuous distribution of the values with no obvious modal values.
Second, no adjustments for main confounding clinical variables were performed. For smoking it would have been a catch-22: (a) smokers have lower 25(OH)D (Tønnesen et al, 2016); (b) 25(OH)D is associated with higher risk of tobacco-related cancers (Afzal et al, 2013). Similarly, alcohol consumption, obesity, overweight, insulin resistance, type 2 diabetes have an impact on vitamin D status (Palaniswamy et al, 2017).
Long ago, in 1998, a prospective survey (NHANES III) investigated 25(OH)D levels with mortality, accounting for age, sex, ethnicity, diabetes, current smoking, body mass index, physical activity, supplementation, season and so on (Melamed et al, 2008). Personalised medicine is first about phenotyping not genotyping!
References
Afzal S, Bojesen SE, Nordestgaard BG (2013) Low plasma 25-hydroxyvitamin D and risk of tobacco-related cancer. Clin Chem 59: 771–780.
Melamed ML, Michos ED, Post W, Astor B (2008) 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 168: 1629–1637.
Palaniswamy S, Hyppönen E, Williams D, Jokelainen J, Lowry E, Keinänen-Kiukaanniemi S, Herzig KH, Järvelin MR, Sebert S (2017) Potential determinants of vitamin D in Finnish adults: a cross-sectional study from the Northern Finland birth cohort 1966. BMJ Open 7: e013161.
Tønnesen R, Hovind PH, Jensen LT, Schwarz P (2016) Determinants of vitamin D status in young adults: influence of lifestyle, sociodemographic and anthropometric factors. BMC Public Health 16: 385.
Vaughan-Shaw PG, O'Sullivan F, Farrington SM, Theodoratou E, Campbell H, Dunlop MG, Zgaga L (2017) The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. Br J Cancer 116: 1092–1110.
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Braillon, A. Comment on 'The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis'. Br J Cancer 117, e3 (2017). https://doi.org/10.1038/bjc.2017.184
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DOI: https://doi.org/10.1038/bjc.2017.184