Is high vitamin B12 status a cause of lung cancer?

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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.

Original languageEnglish
Pages (from-to)1499-1503
Number of pages5
JournalInternational Journal of Cancer
Issue number6
StatePublished - Sep 15 2019

Bibliographical note

Funding Information:
The Lung Cancer Cohort Consortium (LC3) was supported by National Institutes of Health/National Cancer Institute grant No. 1U01CA155340. The Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by (U19-CA148127 and CA148127S1). The ILCCO data harmonization is supported by Cancer Care Ontario Research Chair of Population Studies to R.H. and Lunenfeld-Tanenbaum Research Institute, Sinai Health System. The TRICL-ILCCO OncoArray was supported by in-kind genotyping by the Centre for Inherited Disease Research (26820120008i-0-26800068-1). The work of TLL was undertaken during a postdoctoral placement at the International Agency for Research on Cancer, within the framework of an agreement between the Research Council of Norway and the Norwegian University of Science and Technology. The funding organizations had no role in design and conduct of the study; collection, management,analysis and interpretation of the data; preparation, review, or approval of the study. The authors would like to thank all cohort participants and staff, including but not limited to, the participants and staff of the Health Professionals Follow-up Study and Nurses' Health Study for their valuable contribution as well as the after state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY.

Publisher Copyright:
© 2018 International Agency for Research on Cancer (IARC/WHO); licensed by UICC

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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