The causal roles of vitamin B(12) and transcobalamin in prostate cancer:can Mendelian randomization analysis provide definitive answers?

Collin, Simon M. and Metcalfe, Chris and Palmer, Tom M. and Refsum, Helga and Lewis, Sarah J. and Smith, George Davey and Cox, Angela and Davis, Michael and Marsden, Gemma and Johnston, Carole and Lane, J. Athene and Donovan, Jenny L. and Neal, David E. and Hamdy, Freddie C. and Smith, A. David and Martin, Richard M. (2011) The causal roles of vitamin B(12) and transcobalamin in prostate cancer:can Mendelian randomization analysis provide definitive answers? International Journal of Molecular Epidemiology and Genetics, 2 (4). pp. 316-327.

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Abstract

Circulating vitamin B(12) (cobalamin/B(12)) and total transcobalamin (tTC) have been associated with increased and reduced risk, respectively, of prostate cancer. Mendelian randomization has the potential to determine whether these are causal associations. We estimated associations of single nucleotide polymorphisms in B(12)-related genes (MTR, MTRR, FUT2, TCN2, TCN1, CUBN, and MUT) with plasma concentrations of B(12), tTC, holo-transcobalamin, holo-haptocorrin, folate, and homocysteine and with prostate cancer risk in a case-control study (913 cases, 895 controls) nested within the UK-wide population-based ProtecT study of prostate cancer in men age 45-69 years. Instrumental variable (IV) analysis was used to estimate odds ratios for effects of B(12) and tTC on prostate cancer. We observed that B(12) was lower in men with FUT2 204G>A (rs492602), CUBN 758C>T (rs1801222) and MUT 1595G>A (rs1141321) alleles (P(trend)<0.001); tTC was lower in men with the TCN2 776C>G (rs1801198) allele (P(trend)<0.001). FUT2 204G>A and CUBN 758C>T were selected as instruments for B(12); TCN2 776C>G for tTC. Conventional and IV estimates for the association of log(e)(B(12)) with prostate cancer were: OR=1.17 (95% CI 0.90-1.51), P=0.2 and OR=0.60 (0.16-2.15), P=0.4, respectively. Conventional and IV estimates for the association of loge(tTC) with prostate cancer were: OR=0.81 (0.54-1.20), P=0.3 and OR=0.41 (0.13-1.32), P=0.1, respectively. Confidence intervals around the IV estimates in our study were too wide to allow robust inference. Sample size estimates based on our data indicated that Mendelian randomization in this context requires much larger studies or multiple genetic variants that explain all of the variance in the intermediate phenotype.

Item Type: Journal Article
Journal or Publication Title: International Journal of Molecular Epidemiology and Genetics
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/2700/2713
Subjects:
Departments: Faculty of Science and Technology > Mathematics and Statistics
ID Code: 73921
Deposited By: ep_importer_pure
Deposited On: 18 Jun 2015 05:56
Refereed?: Yes
Published?: Published
Last Modified: 01 Jan 2020 09:14
URI: https://eprints.lancs.ac.uk/id/eprint/73921

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