Is high vitamin B12 status a cause of lung cancer

Published on Jan 15, 2019in International Journal of Cancer4.98
· DOI :10.1002/ijc.32033
Anouar Fanidi9
Estimated H-index: 9
(University of Cambridge),
Anouar Fanidi (University of Cambridge)+ 47 AuthorsPaul Brennan92
Estimated H-index: 92
(IARC: International Agency for Research on Cancer)
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 [OR log2B12 ] = 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 [OR SD ] = 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. © 2018 International Agency for Research on Cancer (IARC/WHO); licensed by UICC
  • References (15)
  • Citations (1)
Published on Jan 1, 2018in Journal of the National Cancer Institute10.21
Anouar Fanidi9
Estimated H-index: 9
(IARC: International Agency for Research on Cancer),
David C. Muller16
Estimated H-index: 16
(Imperial College London)
+ 55 AuthorsQiuyin Cai64
Estimated H-index: 64
Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospecti ...
Published on Oct 20, 2017in Journal of Clinical Oncology28.25
Theodore M. Brasky16
Estimated H-index: 16
Emily White63
Estimated H-index: 63
Chi-Ling Chen2
Estimated H-index: 2
PurposeInconsistent findings have been reported of a link between the use of one-carbon metabolism–related B vitamins and lung cancer risk. Because of the high prevalence of supplemental vitamin B use, any possible increased association warrants further investigation. We examined the association between long-term use of supplemental B vitamins on the one-carbon metabolism pathway and lung cancer risk in the Vitamins and Lifestyle (VITAL) cohort, which was designed specifically to look at supplem...
Published on Jul 1, 2017in Nature Genetics25.45
James D. McKay50
Estimated H-index: 50
(IARC: International Agency for Research on Cancer),
Rayjean J. Hung45
Estimated H-index: 45
(U of T: University of Toronto)
+ 137 AuthorsYafang Li10
Estimated H-index: 10
(Dartmouth College)
Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striki...
Published on Sep 11, 2016in International Journal of Epidemiology7.34
Jack Bowden19
Estimated H-index: 19
(UoB: University of Bristol),
Fabiola Del Greco M16
Estimated H-index: 16
+ 3 AuthorsJohn R. Thompson68
Estimated H-index: 68
(University of Leicester)
Published on Sep 15, 2014in Human Molecular Genetics4.54
George Davey-Smith177
Estimated H-index: 177
(UoB: University of Bristol),
Gibran Hemani24
Estimated H-index: 24
(UoB: University of Bristol)
Observational epidemiological studies are prone to confounding, reverse causation and various biases and have generated findings that have proved to be unreliable indicators of the causal effects of modifiable exposures on disease outcomes. Mendelian randomization (MR) is a method that utilizes genetic variants that are robustly associated with such modifiable exposures to generate more reliable evidence regarding which interventions should produce health benefits. The approach is being widely a...
Published on Nov 1, 2013in Genetic Epidemiology2.50
Stephen Burgess41
Estimated H-index: 41
(University of Cambridge),
Adam S. Butterworth38
Estimated H-index: 38
(University of Cambridge),
Simon G. Thompson95
Estimated H-index: 95
(University of Cambridge)
Genome-wide association studies, which typically report regression coefficients summarizing the associations of many genetic variants with various traits, are potentially a powerful source of data for Mendelian randomization investigations. We demonstrate how such coefficients from multiple variants can be combined in a Mendelian randomization analysis to estimate the causal effect of a risk factor on an outcome. The bias and efficiency of estimates based on summarized data are compared to those...
Published on Jun 6, 2013in PLOS Genetics5.22
Niels Grarup51
Estimated H-index: 51
(UCPH: University of Copenhagen),
Patrick Sulem67
Estimated H-index: 67
(deCODE genetics)
+ 27 AuthorsThomas Sparsø25
Estimated H-index: 25
(UCPH: University of Copenhagen)
Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture ...
Published on Jun 16, 2010in JAMA51.27
Mattias Johansson40
Estimated H-index: 40
Caroline L. Relton48
Estimated H-index: 48
+ 42 AuthorsFrançoise Clavel-Chapelon91
Estimated H-index: 91
CONTEXT: B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk. OBJECTIVE: To investigate if 1-carbon metabolism factors are associated with onset of lung cancer. DESIGN, SETTING, AND PARTICIPANTS: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from 10 countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were iden...
Published on Nov 18, 2009in JAMA51.27
Marta Ebbing15
Estimated H-index: 15
(Haukeland University Hospital),
Kaare H. Bønaa48
Estimated H-index: 48
(Haukeland University Hospital)
+ 10 AuthorsDennis W.T. Nilsen28
Estimated H-index: 28
Context Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk. Objective To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials. Design, Setting, and Participants Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 683...
Published on May 15, 2009in Rapid Communications in Mass Spectrometry2.04
Øivind Midttun31
Estimated H-index: 31
Steinar Hustad21
Estimated H-index: 21
(University of Bergen),
Per Magne Ueland80
Estimated H-index: 80
(University of Bergen)
Vitamins B2 and B6 serve as cofactors in enzymatic reactions involved in tryptophan and homocysteine metabolism. Plasma concentrations of these vitamins and amino acids are related to smoking and inflammation, and correlate with other markers of immune activation. Large-scale studies of these relations have been hampered by lack of suitable analytical methods. The assay described includes riboflavin, five vitamin B6 forms (pyridoxal 5′-phosphate, pyridoxal, 4-pyridoxic acid, pyridoxine and pyrid...
Cited By1
Published on 2019in International Journal of Epidemiology7.34
Daniela Mariosa (IARC: International Agency for Research on Cancer), Robert Carreras-Torres7
Estimated H-index: 7
(IARC: International Agency for Research on Cancer)
+ 2 AuthorsPaul Brennan92
Estimated H-index: 92
(IARC: International Agency for Research on Cancer)
Published on Mar 5, 2019in European Journal of Nutrition4.45
Yumie Takata10
Estimated H-index: 10
(Vandy: Vanderbilt University),
Xiao-Ou Shu96
Estimated H-index: 96
(Vandy: Vanderbilt University)
+ 6 AuthorsQiuyin Cai64
Estimated H-index: 64
(Vandy: Vanderbilt University)
Purpose We prospectively examined associations of lung cancer risk with food intake of B vitamins involved in one-carbon metabolism and the use of folic acid-containing supplements among a low-income population of black and white adults in the Southeastern US.
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