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Is high vitamin B12 status a cause of lung cancer?

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 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.

SUBMITTER: Fanidi A

PROVIDER: S-EPMC6642017 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Is high vitamin B12 status a cause of lung cancer?

Fanidi Anouar A Carreras-Torres Robert R Larose Tricia L TL Yuan Jian-Min JM Stevens Victoria L VL Weinstein Stephanie J SJ Albanes Demetrius D Prentice Ross R Pettinger Mary M Cai Qiuyin Q Blot William J WJ Arslan Alan A AA Zeleniuch-Jacquotte Anne A McCullough Marjorie L ML Le Marchand Loic L Wilkens Lynne R LR Haiman Christopher A CA Zhang Xuehong X Stampfer Meir J MJ Smith-Warner Stephanie A SA Giovannucci Edward E Giles Graham G GG Hodge Allison M AM Severi Gianluca G Johansson Mikael M Grankvist Kjell K Langhammer Arnulf A Brumpton Ben M BM Wang Renwei R Gao Yu-Tang YT Ericson Ulrika U Bojesen Stig E SE Arnold Susanne M SM Koh Woon-Puay WP Shu Xiao-Ou XO Xiang Yong-Bing YB Li Honglan H Zheng Wei W Lan Qing Q Visvanathan Kala K Hoffman-Bolton Judith J Ueland Per M PM Midttun Øivind Ø Caporaso Neil E NE Purdue Mark M Freedman Neal D ND Buring Julie E JE Lee I-Min IM Sesso Howard D HD Michael Gaziano J J Manjer Jonas J Relton Caroline L CL Hung Rayjean J RJ Amos Chris I CI Johansson Mattias M Brennan Paul P

International journal of cancer 20190115 6

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 29,2 ...[more]

PMID: 30499135

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Project description:BackgroundVitamin B12 is an essential micronutrient in humans needed for health maintenance. Deficiency of vitamin B12 has been linked to dietary, environmental and genetic factors. Evidence for the genetic basis of vitamin B12 status is poorly understood. However, advancements in genomic techniques have increased the knowledge-base of the genetics of vitamin B12 status. Based on the candidate gene and genome-wide association (GWA) studies, associations between genetic loci in several genes involved in vitamin B12 metabolism have been identified.ObjectiveThe objective of this literature review was to identify and discuss reports of associations between single-nucleotide polymorphisms (SNPs) in vitamin B12 pathway genes and their influence on the circulating levels of vitamin B12.MethodsRelevant articles were obtained through a literature search on PubMed through to May 2017. An article was included if it examined an association of a SNP with serum or plasma vitamin B12 concentration. Beta coefficients and odds ratios were used to describe the strength of an association, and a P < 0.05 was considered as statistically significant. Two reviewers independently evaluated the eligibility for the inclusion criteria and extracted the data.ResultsFrom 23 studies which fulfilled the selection criteria, 16 studies identified SNPs that showed statistically significant associations with vitamin B12 concentrations. Fifty-nine vitamin B12-related gene polymorphisms associated with vitamin B12 status were identified in total, from the following populations: African American, Brazilian, Canadian, Chinese, Danish, English, European ancestry, Icelandic, Indian, Italian, Latino, Northern Irish, Portuguese and residents of the USA.ConclusionOverall, the data analyzed suggests that ethnic-specific associations are involved in the genetic determination of vitamin B12 concentrations. However, despite recent success in genetic studies, the majority of identified genes that could explain variation in vitamin B12 concentrations were from Caucasian populations. Further research utilizing larger sample sizes of non-Caucasian populations is necessary in order to better understand these ethnic-specific associations.

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Is high vitamin B12 status a cause of lung cancer?

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Is high vitamin B12 status a cause of lung cancer?

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