Is high vitamin B12 status a cause of lung cancer?

TY - JOUR

T1 - Is high vitamin B12 status a cause of lung cancer?

AU - Fanidi, Anouar

AU - Carreras-Torres, Robert

AU - Larose, Tricia L.

AU - Yuan, Jian Min

AU - Stevens, Victoria L.

AU - Weinstein, Stephanie J.

AU - Albanes, Demetrius

AU - Prentice, Ross

AU - Pettinger, Mary

AU - Cai, Qiuyin

AU - Blot, William J.

AU - Arslan, Alan A.

AU - Zeleniuch-Jacquotte, Anne

AU - McCullough, Marjorie L.

AU - Le Marchand, Loic

AU - Wilkens, Lynne R.

AU - Haiman, Christopher A.

AU - Zhang, Xuehong

AU - Stampfer, Meir J.

AU - Smith-Warner, Stephanie A.

AU - Giovannucci, Edward

AU - Giles, Graham G.

AU - Hodge, Allison M.

AU - Severi, Gianluca

AU - Johansson, Mikael

AU - Grankvist, Kjell

AU - Langhammer, Arnulf

AU - Brumpton, Ben M.

AU - Wang, Renwei

AU - Gao, Yu Tang

AU - Ericson, Ulrika

AU - Bojesen, Stig E.

AU - Arnold, Susanne M.

AU - Koh, Woon Puay

AU - Shu, Xiao Ou

AU - Xiang, Yong Bing

AU - Li, Honglan

AU - Zheng, Wei

AU - Lan, Qing

AU - Visvanathan, Kala

AU - Hoffman-Bolton, Judith

AU - Ueland, Per M.

AU - Midttun, Øivind

AU - Caporaso, Neil E.

AU - Purdue, Mark

AU - Freedman, Neal D.

AU - Buring, Julie E.

AU - Lee, I. Min

AU - Sesso, Howard D.

AU - Michael Gaziano, J.

AU - on behalf of the LC3 consortium and the TRICL consortium

PY - 2019/9/15

Y1 - 2019/9/15

N2 - 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.

AB - 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.

U2 - 10.1002/ijc.32033

DO - 10.1002/ijc.32033

M3 - Journal article

C2 - 30499135

AN - SCOPUS:85060173493

SN - 0020-7136

JO - International Journal of Cancer

JF - International Journal of Cancer

ER -