Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3)

Anouar Fanidi, David C. Muller, Jian Min Yuan, Victoria L. Stevens, Stephanie J. Weinstein, Demetrius Albanes, Ross Prentice, Cynthia A. Thomsen, Mary Pettinger, Qiuyin Cai, William J. Blot, Jie Wu, Alan A. Arslan, Anne Zeleniuch-Jacquotte, Marjorie L. McCullough, Loic Le Marchand, Lynne R. Wilkens, Christopher A. Haiman, Xuehong Zhang, Jiali Han & 2 others Mattias Johansson, Paul Brennan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.

Original languageEnglish (US)
Article numberdjx119
JournalJournal of the National Cancer Institute
Volume110
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

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Vitamin B 6
Folic Acid
Methionine
Lung Neoplasms
Confidence Intervals
Tobacco
Logistic Models
Cotinine
Vitamin B Complex
National Cancer Institute (U.S.)
Causality
Case-Control Studies
Carbon
Biomarkers
Smoking
Odds Ratio
Population
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Fanidi, A., Muller, D. C., Yuan, J. M., Stevens, V. L., Weinstein, S. J., Albanes, D., ... Brennan, P. (2018). Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3). Journal of the National Cancer Institute, 110(1), [djx119]. https://doi.org/10.1093/jnci/djx119

Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3). / Fanidi, Anouar; Muller, David C.; Yuan, Jian Min; Stevens, Victoria L.; Weinstein, Stephanie J.; Albanes, Demetrius; Prentice, Ross; Thomsen, Cynthia A.; Pettinger, Mary; Cai, Qiuyin; Blot, William J.; Wu, Jie; Arslan, Alan A.; Zeleniuch-Jacquotte, Anne; McCullough, Marjorie L.; Le Marchand, Loic; Wilkens, Lynne R.; Haiman, Christopher A.; Zhang, Xuehong; Han, Jiali; Johansson, Mattias; Brennan, Paul.

In: Journal of the National Cancer Institute, Vol. 110, No. 1, djx119, 01.01.2018.

Research output: Contribution to journalArticle

Fanidi, A, Muller, DC, Yuan, JM, Stevens, VL, Weinstein, SJ, Albanes, D, Prentice, R, Thomsen, CA, Pettinger, M, Cai, Q, Blot, WJ, Wu, J, Arslan, AA, Zeleniuch-Jacquotte, A, McCullough, ML, Le Marchand, L, Wilkens, LR, Haiman, CA, Zhang, X, Han, J, Johansson, M & Brennan, P 2018, 'Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3)', Journal of the National Cancer Institute, vol. 110, no. 1, djx119. https://doi.org/10.1093/jnci/djx119
Fanidi, Anouar ; Muller, David C. ; Yuan, Jian Min ; Stevens, Victoria L. ; Weinstein, Stephanie J. ; Albanes, Demetrius ; Prentice, Ross ; Thomsen, Cynthia A. ; Pettinger, Mary ; Cai, Qiuyin ; Blot, William J. ; Wu, Jie ; Arslan, Alan A. ; Zeleniuch-Jacquotte, Anne ; McCullough, Marjorie L. ; Le Marchand, Loic ; Wilkens, Lynne R. ; Haiman, Christopher A. ; Zhang, Xuehong ; Han, Jiali ; Johansson, Mattias ; Brennan, Paul. / Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3). In: Journal of the National Cancer Institute. 2018 ; Vol. 110, No. 1.
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abstract = "Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1) being 0.88 (95{\%} confidence interval [CI] = 0.78 to 1.00) and 0.86 (95{\%} CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95{\%} CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95{\%} CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95{\%} CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95{\%} CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.",
author = "Anouar Fanidi and Muller, {David C.} and Yuan, {Jian Min} and Stevens, {Victoria L.} and Weinstein, {Stephanie J.} and Demetrius Albanes and Ross Prentice and Thomsen, {Cynthia A.} and Mary Pettinger and Qiuyin Cai and Blot, {William J.} and Jie Wu and Arslan, {Alan A.} and Anne Zeleniuch-Jacquotte and McCullough, {Marjorie L.} and {Le Marchand}, Loic and Wilkens, {Lynne R.} and Haiman, {Christopher A.} and Xuehong Zhang and Jiali Han and Mattias Johansson and Paul Brennan",
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AU - Fanidi, Anouar

AU - Muller, David C.

AU - Yuan, Jian Min

AU - Stevens, Victoria L.

AU - Weinstein, Stephanie J.

AU - Albanes, Demetrius

AU - Prentice, Ross

AU - Thomsen, Cynthia A.

AU - Pettinger, Mary

AU - Cai, Qiuyin

AU - Blot, William J.

AU - Wu, Jie

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 - Han, Jiali

AU - Johansson, Mattias

AU - Brennan, Paul

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N2 - Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.

AB - Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.

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