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Is high vitamin B12 status a cause of lung cancer?
Author(s) -
Fanidi Anouar,
CarrerasTorres Robert,
Larose Tricia L.,
Yuan JianMin,
Stevens Victoria L.,
Weinstein Stephanie J.,
Albanes Demetrius,
Prentice Ross,
Pettinger Mary,
Cai Qiuyin,
Blot William J.,
Arslan Alan A.,
ZeleniuchJacquotte Anne,
McCullough Marjorie L.,
Le Marchand Loic,
Wilkens Lynne R.,
Haiman Christopher A.,
Zhang Xuehong,
Stampfer Meir J.,
SmithWarner Stephanie A.,
Giovannucci Edward,
Giles Graham G.,
Hodge Allison M.,
Severi Gianluca,
Johansson Mikael,
Grankvist Kjell,
Langhammer Arnulf,
Brumpton Ben M.,
Wang Renwei,
Gao YuTang,
Ericson Ulrika,
Bojesen Stig E.,
Arnold Susanne M.,
Koh WoonPuay,
Shu XiaoOu,
Xiang YongBing,
Li Honglan,
Zheng Wei,
Lan Qing,
Visvanathan Kala,
HoffmanBolton Judith,
Ueland Per M.,
Midttun Øivind,
Caporaso Neil E.,
Purdue Mark,
Freedman Neal D.,
Buring Julie E.,
Lee IMin,
Sesso Howard D.,
Michael Gaziano J.,
Manjer Jonas,
Relton Caroline L.,
Hung Rayjean J.,
Amos Chris I.,
Johansson Mattias,
Brennan Paul
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32033
Subject(s) - mendelian randomization , nested case control study , vitamin b12 , lung cancer , medicine , odds ratio , case control study , cancer , prospective cohort study , biomarker , oncology , physiology , gastroenterology , genotype , biology , genetics , genetic variants , gene
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.