Folate-related genes and the risk of tobacco-related cancers in Central Europe

Rayjean J. Hung, Mia Hashibe, James McKay, Valerie Gaborieau, Neonila Szeszenia-Dabrowska, David Zaridze, Jolanta Lissowska, P. Rudnai, Eleonora Fabianova, Ioan Mates, Lenka Foretova, Vadimir Janout, Vladimir Bencko, Amelie Chabrier, Norman Moullan, Federico Canzian, Janet Hall, Paolo Boffetta, Paul Brennan

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95% confidence interval (CI) =1.10-;1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR=1.92,95% CI =1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95% CI =1.39-4.88) and 4.14 (95% CI =1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers.

Original languageEnglish
Pages (from-to)1334-1340
Number of pages7
JournalCarcinogenesis
Volume28
Issue number6
DOIs
Publication statusPublished - Jun 2007

Fingerprint

Folic Acid
Tobacco
Methylenetetrahydrofolate Reductase (NADPH2)
Genes
Neoplasms
Confidence Intervals
Lung Neoplasms
Gastrointestinal Tract
Odds Ratio
Genotype
Lung
Linkage Disequilibrium
Homozygote
Haplotypes
Multicenter Studies
Life Style

ASJC Scopus subject areas

  • Cancer Research

Cite this

Hung, R. J., Hashibe, M., McKay, J., Gaborieau, V., Szeszenia-Dabrowska, N., Zaridze, D., ... Brennan, P. (2007). Folate-related genes and the risk of tobacco-related cancers in Central Europe. Carcinogenesis, 28(6), 1334-1340. https://doi.org/10.1093/carcin/bgm067

Folate-related genes and the risk of tobacco-related cancers in Central Europe. / Hung, Rayjean J.; Hashibe, Mia; McKay, James; Gaborieau, Valerie; Szeszenia-Dabrowska, Neonila; Zaridze, David; Lissowska, Jolanta; Rudnai, P.; Fabianova, Eleonora; Mates, Ioan; Foretova, Lenka; Janout, Vadimir; Bencko, Vladimir; Chabrier, Amelie; Moullan, Norman; Canzian, Federico; Hall, Janet; Boffetta, Paolo; Brennan, Paul.

In: Carcinogenesis, Vol. 28, No. 6, 06.2007, p. 1334-1340.

Research output: Contribution to journalArticle

Hung, RJ, Hashibe, M, McKay, J, Gaborieau, V, Szeszenia-Dabrowska, N, Zaridze, D, Lissowska, J, Rudnai, P, Fabianova, E, Mates, I, Foretova, L, Janout, V, Bencko, V, Chabrier, A, Moullan, N, Canzian, F, Hall, J, Boffetta, P & Brennan, P 2007, 'Folate-related genes and the risk of tobacco-related cancers in Central Europe', Carcinogenesis, vol. 28, no. 6, pp. 1334-1340. https://doi.org/10.1093/carcin/bgm067
Hung RJ, Hashibe M, McKay J, Gaborieau V, Szeszenia-Dabrowska N, Zaridze D et al. Folate-related genes and the risk of tobacco-related cancers in Central Europe. Carcinogenesis. 2007 Jun;28(6):1334-1340. https://doi.org/10.1093/carcin/bgm067
Hung, Rayjean J. ; Hashibe, Mia ; McKay, James ; Gaborieau, Valerie ; Szeszenia-Dabrowska, Neonila ; Zaridze, David ; Lissowska, Jolanta ; Rudnai, P. ; Fabianova, Eleonora ; Mates, Ioan ; Foretova, Lenka ; Janout, Vadimir ; Bencko, Vladimir ; Chabrier, Amelie ; Moullan, Norman ; Canzian, Federico ; Hall, Janet ; Boffetta, Paolo ; Brennan, Paul. / Folate-related genes and the risk of tobacco-related cancers in Central Europe. In: Carcinogenesis. 2007 ; Vol. 28, No. 6. pp. 1334-1340.
@article{06a75258b8564788b1386612d02bf350,
title = "Folate-related genes and the risk of tobacco-related cancers in Central Europe",
abstract = "Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95{\%} confidence interval (CI) =1.10-;1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR=1.92,95{\%} CI =1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95{\%} CI =1.39-4.88) and 4.14 (95{\%} CI =1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers.",
author = "Hung, {Rayjean J.} and Mia Hashibe and James McKay and Valerie Gaborieau and Neonila Szeszenia-Dabrowska and David Zaridze and Jolanta Lissowska and P. Rudnai and Eleonora Fabianova and Ioan Mates and Lenka Foretova and Vadimir Janout and Vladimir Bencko and Amelie Chabrier and Norman Moullan and Federico Canzian and Janet Hall and Paolo Boffetta and Paul Brennan",
year = "2007",
month = "6",
doi = "10.1093/carcin/bgm067",
language = "English",
volume = "28",
pages = "1334--1340",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Folate-related genes and the risk of tobacco-related cancers in Central Europe

AU - Hung, Rayjean J.

AU - Hashibe, Mia

AU - McKay, James

AU - Gaborieau, Valerie

AU - Szeszenia-Dabrowska, Neonila

AU - Zaridze, David

AU - Lissowska, Jolanta

AU - Rudnai, P.

AU - Fabianova, Eleonora

AU - Mates, Ioan

AU - Foretova, Lenka

AU - Janout, Vadimir

AU - Bencko, Vladimir

AU - Chabrier, Amelie

AU - Moullan, Norman

AU - Canzian, Federico

AU - Hall, Janet

AU - Boffetta, Paolo

AU - Brennan, Paul

PY - 2007/6

Y1 - 2007/6

N2 - Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95% confidence interval (CI) =1.10-;1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR=1.92,95% CI =1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95% CI =1.39-4.88) and 4.14 (95% CI =1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers.

AB - Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95% confidence interval (CI) =1.10-;1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR=1.92,95% CI =1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95% CI =1.39-4.88) and 4.14 (95% CI =1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers.

UR - http://www.scopus.com/inward/record.url?scp=34447520377&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447520377&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgm067

DO - 10.1093/carcin/bgm067

M3 - Article

C2 - 17389614

AN - SCOPUS:34447520377

VL - 28

SP - 1334

EP - 1340

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 6

ER -