Is high vitamin B12 status a cause of lung cancer?

September 2019
Anouar Fanidi, PhD, Robert Carreras-Torres, PhD, Tricia L. Larose, PhD, Jian-Min Yuan, MD, PhD, Victoria L. Stevens, PhD, Stephanie J. Weinstein, PhD, Demetrius Albanes, MD, Ross Prentice, PhD, Mary Pettinger, MS, Qiuyin Cai, MD, PhD, William J. Blot, PhD, Alan A. Arslan, MD, Anne Zeleniuch-Jacquotte, MS, MD, Marjorie L. McCullough, ScD, Loic Le Marchand, MD, PhD, Lynne R. Wilkens, DrPH, Christopher A. Haiman, ScD, Xuehong Zhang, MD, ScD, Meir J. Stampfer, MD, DrPH, Stephanie A. Smith-Warner, MS, PhD, Edward Giovannucci, MD, ScD, Graham G. Giles, PhD, Allison M. Hodge, PhD, Gianluca Severi, PhD, Mikael Johansson, MD, PhD, Kjell Grankvist, MD, PhD, Arnulf Langhammer, MD, PhD, Ben M. Brumpton, PhD, Renwei Wang, MD, MS, Yu-Tang Gao, MD, Ulrika Ericson, PhD, Stig Egil Bojesen, MD, Susanne M. Arnold, MD, Woon-Puay Koh, PhD, Xiao-Ou Shu, MD, PhD, MPH, Yong-Bing Xiang, MD, MPH, Honglan Li, MD, Wei Zheng, MD, PhD, MPH, Qing Lan, MD, PhD, Kala Visvanathan, MD, MHS, Judith Hoffman-Bolton, PhD, Per Magne Ueland, MD, PhD, Øivind Midttun, PhD, Neil E. Caporaso, MD, Mark Purdue, PhD, Neal D. Freedman, PhD, Julie E. Buring, ScD, I-Min Lee, ScD, Howard D. Sesso, ScD, MPH, J. Michael Gaziano, MD, MPH, Jonas Manjer, MD, PhD, Caroline L Relton, PhD, Rayjean J Hung, PhD, Chris I Amos, PhD, Mattias Johansson, PhD, and Paul Brennan, PhD1, LC consortium and the TRICL consortium.

Abstract

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 aetiology 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 5,183 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.