Is high vitamin B12 status a cause of lung cancer?

Anouar Fanidi^{1

2}, Robert Carreras-Torres¹, Tricia L Larose^{1

3}, Jian-Min Yuan^{4

5}, Victoria L Stevens⁶, Stephanie J Weinstein⁷, Demetrius Albanes⁷, Ross Prentice⁸, Mary Pettinger⁸, Qiuyin Cai⁹, William J Blot^{9

10}, Alan A Arslan¹¹, Anne Zeleniuch-Jacquotte¹², Marjorie L McCullough⁶, Loic Le Marchand¹³, Lynne R Wilkens¹³, Christopher A Haiman¹⁴, Xuehong Zhang¹⁵, Meir J Stampfer^{15

16

17}, Stephanie A Smith-Warner^{16

17}, Edward Giovannucci^{15

16

17}, Graham G Giles^{18

19}, Allison M Hodge^{18

19}, Gianluca Severi^{18

20

21}, Mikael Johansson²², Kjell Grankvist²³, Arnulf Langhammer²⁴, Ben M Brumpton³, Renwei Wang⁴, Yu-Tang Gao²⁵, Ulrika Ericson^{26

27}, Stig E Bojesen²⁶, Susanne M Arnold²⁸, Woon-Puay Koh²⁹, Xiao-Ou Shu⁹, Yong-Bing Xiang²⁵, Honglan Li⁷, Wei Zheng⁹, Qing Lan⁷, Kala Visvanathan³⁰, Judith Hoffman-Bolton³⁰, Per M Ueland^{31

32}, Øivind Midttun³³, Neil E Caporaso⁷, Mark Purdue⁷, Neal D Freedman⁷, Julie E Buring^{16

34

35}, I-Min Lee^{16

34}, Howard D Sesso^{16

34

35}, J Michael Gaziano^{34

35

36}, Jonas Manjer³⁷, Caroline L Relton^{38

39}, Rayjean J Hung⁴⁰, Chris I Amos⁴¹, Mattias Johansson¹, Paul Brennan¹; LC3 consortium and the TRICL consortium

Affiliations

¹ Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
² MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
³ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA.
⁵ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
⁶ Epidemiology Research Program, American Cancer Society, Inc., Atlanta, GA.
⁷ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
⁸ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
⁹ Health Promotion Sciences, Division of Epidemiology, Department of Medicine,Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN.
¹⁰ International Epidemiology Institute, Rockville, MD.
¹¹ Department of Obstetrics and Gynecology, Population Health and Environmental Medicine, New York University School of Medicine, New York, NY.
¹² Department of Population Health, New York University School of Medicine, New York, NY.
¹³ Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI.
¹⁴ Keck School of Medicine, University of Southern California, Los Angeles, CA.
¹⁵ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
¹⁶ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA.
¹⁷ Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA.
¹⁸ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
¹⁹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
²⁰ Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino, Italy.
²¹ Inserm (Institut National de la Sante et de la Recherche Medicale), Centre for Research in Epidemiology and Population Health, Villejuif, France.
²² Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
²³ Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
²⁴ HUNT Research Centre, Department of Public Health and General Practice, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
²⁵ Department of Epidemiology, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai, China.
²⁶ Diabetes and Cardiovascular disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University Malmö, Lund, Sweden.
²⁷ Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
²⁸ UK Markey Cancer Center, University of Kentuky, Lexington, KY.
²⁹ Duke-NUS Graduate Medical School, Singapore, Singapore.
³⁰ Department of Epidemiology, George W Comstock Center for Public Health Research and Prevention Health Monitoring Unit, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
³¹ Laboratory of Clinical Biochemistry, Department of Clinical Science, University of Bergen, Bergen, Norway.
³² Haukeland University Hospital, Bergen, Norway.
³³ Bevital AS, Bergen, Norway.
³⁴ Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
³⁵ Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
³⁶ Boston VA Medical Center, Boston, MA.
³⁷ Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
³⁸ Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
³⁹ MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
⁴⁰ Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
⁴¹ Department of Biomedical Data Science, Geisel School of medicine, Dartmouth College, Lebanon, PA.

PMID: 30499135
PMCID: PMC6642017
DOI: 10.1002/ijc.32033

Is high vitamin B12 status a cause of lung cancer?

Anouar Fanidi et al. Int J Cancer. 2019.

. 2019 Sep 15;145(6):1499-1503.

doi: 10.1002/ijc.32033. Epub 2019 Jan 15.

Authors

Affiliations

¹ Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
² MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
³ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA.
⁵ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
⁶ Epidemiology Research Program, American Cancer Society, Inc., Atlanta, GA.
⁷ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
⁸ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
⁹ Health Promotion Sciences, Division of Epidemiology, Department of Medicine,Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN.
¹⁰ International Epidemiology Institute, Rockville, MD.
¹¹ Department of Obstetrics and Gynecology, Population Health and Environmental Medicine, New York University School of Medicine, New York, NY.
¹² Department of Population Health, New York University School of Medicine, New York, NY.
¹³ Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI.
¹⁴ Keck School of Medicine, University of Southern California, Los Angeles, CA.
¹⁵ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
¹⁶ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA.
¹⁷ Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA.
¹⁸ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
¹⁹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
²⁰ Molecular end Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino, Italy.
²¹ Inserm (Institut National de la Sante et de la Recherche Medicale), Centre for Research in Epidemiology and Population Health, Villejuif, France.
²² Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
²³ Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
²⁴ HUNT Research Centre, Department of Public Health and General Practice, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
²⁵ Department of Epidemiology, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai, China.
²⁶ Diabetes and Cardiovascular disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University Malmö, Lund, Sweden.
²⁷ Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
²⁸ UK Markey Cancer Center, University of Kentuky, Lexington, KY.
²⁹ Duke-NUS Graduate Medical School, Singapore, Singapore.
³⁰ Department of Epidemiology, George W Comstock Center for Public Health Research and Prevention Health Monitoring Unit, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
³¹ Laboratory of Clinical Biochemistry, Department of Clinical Science, University of Bergen, Bergen, Norway.
³² Haukeland University Hospital, Bergen, Norway.
³³ Bevital AS, Bergen, Norway.
³⁴ Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
³⁵ Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
³⁶ Boston VA Medical Center, Boston, MA.
³⁷ Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
³⁸ Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom.
³⁹ MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
⁴⁰ Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
⁴¹ Department of Biomedical Data Science, Geisel School of medicine, Dartmouth College, Lebanon, PA.

PMID: 30499135
PMCID: PMC6642017
DOI: 10.1002/ijc.32033

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 [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.

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Conflict of interest statement

Conflicts of interest

The authors have no competing interests to report.

Figures

**Figure 1**
Forest plot showing the relationship between circulating vitamin B12 and lung cancer risk from the LC3 and a Mendelian randomization analysis. Footnote: *LC3 odds ratios (OR) indicate relative risks of a doubling in circulating concentrations (base 2 logarithm transformed) adjusted for cotinine and education when relevant (95%CI: 95% confidence intervals). † Mendelian randomization ORs indicate the odds for a one standard deviation (SD) increase in circulating concentrations (approximately 150 pmol/L). ‡ P heterogeneity indicates results of chi-square test assessing the null hypothesis of ORs being the identical.

See this image and copyright information in PMC

References

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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?

Authors

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Abstract

Conflict of interest statement

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