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

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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The causal roles of vitamin B(12) and transcobalamin in prostate cancer: can Mendelian randomization analysis provide definitive answers? / Collin, Simon M.; Metcalfe, Chris; Palmer, Tom M. et al.
In: International Journal of Molecular Epidemiology and Genetics, Vol. 2, No. 4, 2011, p. 316-327.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Collin, SM, Metcalfe, C, Palmer, TM, Refsum, H, Lewis, SJ, Smith, GD, Cox, A, Davis, M, Marsden, G, Johnston, C, Lane, JA, Donovan, JL, Neal, DE, Hamdy, FC, Smith, AD & Martin, RM 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, vol. 2, no. 4, pp. 316-327. <http://www.ijmeg.org/IJMEG1107004A.html>

APA

Collin, S. M., Metcalfe, C., Palmer, T. M., Refsum, H., Lewis, S. J., Smith, G. D., Cox, A., Davis, M., Marsden, G., Johnston, C., Lane, J. A., Donovan, J. L., Neal, D. E., Hamdy, F. C., Smith, A. D., & Martin, R. 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), 316-327. http://www.ijmeg.org/IJMEG1107004A.html

Vancouver

Collin SM, Metcalfe C, Palmer TM, Refsum H, Lewis SJ, Smith GD et al. 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. 2011;2(4):316-327.

Author

Collin, Simon M. ; Metcalfe, Chris ; Palmer, Tom M. et al. / The causal roles of vitamin B(12) and transcobalamin in prostate cancer : can Mendelian randomization analysis provide definitive answers?. In: International Journal of Molecular Epidemiology and Genetics. 2011 ; Vol. 2, No. 4. pp. 316-327.

Bibtex

@article{c41b4c700a4f42cbb78a0a9b16c78e9f,
title = "The causal roles of vitamin B(12) and transcobalamin in prostate cancer: can Mendelian randomization analysis provide definitive answers?",
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.",
keywords = "Vitamin B12/cobalamin, transcobalamin, prostate cancer, Mendelian Randomization",
author = "Collin, {Simon M.} and Chris Metcalfe and Palmer, {Tom M.} and Helga Refsum and Lewis, {Sarah J.} and Smith, {George Davey} and Angela Cox and Michael Davis and Gemma Marsden and Carole Johnston and Lane, {J. Athene} and Donovan, {Jenny L.} and Neal, {David E.} and Hamdy, {Freddie C.} and Smith, {A. David} and Martin, {Richard M.}",
year = "2011",
language = "English",
volume = "2",
pages = "316--327",
journal = "International Journal of Molecular Epidemiology and Genetics",
publisher = "e-Century Publishing Corporation",
number = "4",

}

RIS

TY - JOUR

T1 - The causal roles of vitamin B(12) and transcobalamin in prostate cancer

T2 - can Mendelian randomization analysis provide definitive answers?

AU - Collin, Simon M.

AU - Metcalfe, Chris

AU - Palmer, Tom M.

AU - Refsum, Helga

AU - Lewis, Sarah J.

AU - Smith, George Davey

AU - Cox, Angela

AU - Davis, Michael

AU - Marsden, Gemma

AU - Johnston, Carole

AU - Lane, J. Athene

AU - Donovan, Jenny L.

AU - Neal, David E.

AU - Hamdy, Freddie C.

AU - Smith, A. David

AU - Martin, Richard M.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Vitamin B12/cobalamin

KW - transcobalamin

KW - prostate cancer

KW - Mendelian Randomization

M3 - Journal article

C2 - 22199995

VL - 2

SP - 316

EP - 327

JO - International Journal of Molecular Epidemiology and Genetics

JF - International Journal of Molecular Epidemiology and Genetics

IS - 4

ER -