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A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization.

Jue-Sheng OngSuzanne C Dixon-SuenXikun HanJiyuan Annull nullnull nullUpekha LiyanageJean-Cluade DusingizeJohannes SchumacherInes GockelAnne C BöhmerJanusz JankowskiClaire PallesTracy A O'MaraAmanda B SpurdleMatthew H LawMark M IlesPaul David Peter PharoahAndrew BerchuckQuan LongAaron P ThriftCatherine M OlsenRachel E NealePuya GharahkhaniPenelope M WebbStuart Macgregor
Published in: Nature communications (2021)
Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.
Keyphrases
  • papillary thyroid
  • magnetic resonance
  • childhood cancer
  • copy number
  • lymph node metastasis
  • basal cell carcinoma
  • young adults
  • squamous cell carcinoma
  • case control
  • computed tomography
  • clinical evaluation