Comment on 'The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis'.

Sir,

Vaughan-Shaw 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 ); (b) 25(OH)D is associated with higher risk of tobacco-related cancers (Afzal ). Similarly, alcohol consumption, obesity, overweight, insulin resistance, type 2 diabetes have an impact on vitamin D status (Palaniswamy ).

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 ). Personalised medicine is first about phenotyping not genotyping!