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Lookup NU author(s): Professor Caroline Relton
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© 2018 International Agency for Research on Cancer (IARC/WHO); licensed by UICC Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case–control study, complemented with a Mendelian randomization (MR) approach in an independent case–control sample. We used pre-diagnostic biomarker data from 5183 case–control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case–control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12] = 1.15, 95% confidence interval (95%CI) = 1.06–1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD] = 1.08, 95%CI = 1.00–1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.
Author(s): Fanidi A, Carreras-Torres R, Larose TL, Yuan J-M, Stevens VL, Weinstein SJ, Albanes D, Prentice R, Pettinger M, Cai Q, Blot WJ, Arslan AA, Zeleniuch-Jacquotte A, McCullough ML, Le Marchand L, Wilkens LR, Haiman CA, Zhang X, Stampfer MJ, Smith-Warner SA, Giovannucci E, Giles GG, Hodge AM, Severi G, Johansson M, Grankvist K, Langhammer A, Brumpton BM, Wang R, Gao Y-T, Ericson U, Bojesen SE, Arnold SM, Koh W-P, Shu X-O, Xiang Y-B, Li H, Zheng W, Lan Q, Visvanathan K, Hoffman-Bolton J, Ueland PM, Midttun O, Caporaso NE, Purdue M, Freedman ND, Buring JE, Lee I-M, Sesso HD, Michael Gaziano J, Manjer J, Relton CL, Hung RJ, Amos CI, Johansson M, Brennan P
Publication type: Article
Publication status: Published
Journal: International Journal of Cancer
Pages: Epub ahead of print
Online publication date: 29/11/2018
Acceptance date: 17/10/2018
ISSN (print): 0020-7136
ISSN (electronic): 1097-0215
Publisher: John Wiley & Sons, Inc.
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