Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals

Esther H. Lips, Valerie Gaborieau, James D. McKay, Amelie Chabrier, Rayjean J. Hung, Paolo Boffetta, Mia Hashibe, David Zaridze, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, P. Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, John K. Field, Triantafillos Liloglou, George Xinarianos, John McLaughlinGeoffrey Liu, Frank Skorpen, Maiken Bratt Elvestad, Kristian Hveem, Lars Vatten, Simone Benhamou, Pagona Lagiou, Ivana Holcátová, Franco Merletti, Kristina Kjaerheim, Antonio Agudo, Xavier Castellsagué, Tatiana V. Macfarlane, Luigi Barzan, Cristina Canova, Ray Lowry, David I. Conway, Ariana Znaor, Claire Healy, Maria Paula Curado, Sergio Koifman, Jose Eluf-Neto, Elena Matos, Ana Menezes, Leticia Fernandez, Andres Metspalu, Simon Heath, Mark Lathrop, Paul Brennan

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Background: Genetic variants in 15q25 have been identified as potential risk markers for lung cancer (LC), but controversy exists as to whether this is a direct association, or whether the 15q variant is simply a proxy for increased exposure to tobacco carcinogens. Methods: We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies. Results: Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P20 CPD) [odds ratio (OR)=1.13, 95% confidence interval (CI) 0.96-1.34, P=0.13 for heterozygotes and 1.81, 95% CI 1.39-2.35 for homozygotes, P-18), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR=1.27, 95% CI 1.19-1.35, P=5 × 10-13). Furthermore, we found an association between the variant allele and an earlier age of LC onset (P=0.02). The association was also noted in UADT cancers (OR=1.08, 95% CI 1.01-1.15, P=0.02). Genome wide association (GWA) analysis of over 300 000 SNPs on 11 219 subjects did not identify any additional variants related to smoking behaviour. Conclusions This study confirms the strong association between 15q gene variants and LC and shows an independent association with smoking quantity, as well as an association with UADT cancers.

Original languageEnglish
Article numberdyp288
Pages (from-to)563-577
Number of pages15
JournalInternational Journal of Epidemiology
Volume39
Issue number2
DOIs
Publication statusPublished - Apr 2010

Fingerprint

Smoking
Lung Neoplasms
Tobacco Products
Confidence Intervals
Genes
Odds Ratio
Neoplasms
Single Nucleotide Polymorphism
Alleles
Genotype
Genome-Wide Association Study
Homozygote
Proxy
Heterozygote
Risk-Taking
Carcinogens
Tobacco

Keywords

  • Lung cancer
  • Nicotine dependence
  • Smoking quantity
  • UADT cancer

ASJC Scopus subject areas

  • Epidemiology

Cite this

Lips, E. H., Gaborieau, V., McKay, J. D., Chabrier, A., Hung, R. J., Boffetta, P., ... Brennan, P. (2010). Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals. International Journal of Epidemiology, 39(2), 563-577. [dyp288]. https://doi.org/10.1093/ije/dyp288

Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals. / Lips, Esther H.; Gaborieau, Valerie; McKay, James D.; Chabrier, Amelie; Hung, Rayjean J.; Boffetta, Paolo; Hashibe, Mia; Zaridze, David; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, P.; Fabianova, Eleonora; Mates, Dana; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Field, John K.; Liloglou, Triantafillos; Xinarianos, George; McLaughlin, John; Liu, Geoffrey; Skorpen, Frank; Elvestad, Maiken Bratt; Hveem, Kristian; Vatten, Lars; Benhamou, Simone; Lagiou, Pagona; Holcátová, Ivana; Merletti, Franco; Kjaerheim, Kristina; Agudo, Antonio; Castellsagué, Xavier; Macfarlane, Tatiana V.; Barzan, Luigi; Canova, Cristina; Lowry, Ray; Conway, David I.; Znaor, Ariana; Healy, Claire; Curado, Maria Paula; Koifman, Sergio; Eluf-Neto, Jose; Matos, Elena; Menezes, Ana; Fernandez, Leticia; Metspalu, Andres; Heath, Simon; Lathrop, Mark; Brennan, Paul.

In: International Journal of Epidemiology, Vol. 39, No. 2, dyp288, 04.2010, p. 563-577.

Research output: Contribution to journalArticle

Lips, EH, Gaborieau, V, McKay, JD, Chabrier, A, Hung, RJ, Boffetta, P, Hashibe, M, Zaridze, D, Szeszenia-Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Mates, D, Bencko, V, Foretova, L, Janout, V, Field, JK, Liloglou, T, Xinarianos, G, McLaughlin, J, Liu, G, Skorpen, F, Elvestad, MB, Hveem, K, Vatten, L, Benhamou, S, Lagiou, P, Holcátová, I, Merletti, F, Kjaerheim, K, Agudo, A, Castellsagué, X, Macfarlane, TV, Barzan, L, Canova, C, Lowry, R, Conway, DI, Znaor, A, Healy, C, Curado, MP, Koifman, S, Eluf-Neto, J, Matos, E, Menezes, A, Fernandez, L, Metspalu, A, Heath, S, Lathrop, M & Brennan, P 2010, 'Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals', International Journal of Epidemiology, vol. 39, no. 2, dyp288, pp. 563-577. https://doi.org/10.1093/ije/dyp288
Lips, Esther H. ; Gaborieau, Valerie ; McKay, James D. ; Chabrier, Amelie ; Hung, Rayjean J. ; Boffetta, Paolo ; Hashibe, Mia ; Zaridze, David ; Szeszenia-Dabrowska, Neonilia ; Lissowska, Jolanta ; Rudnai, P. ; Fabianova, Eleonora ; Mates, Dana ; Bencko, Vladimir ; Foretova, Lenka ; Janout, Vladimir ; Field, John K. ; Liloglou, Triantafillos ; Xinarianos, George ; McLaughlin, John ; Liu, Geoffrey ; Skorpen, Frank ; Elvestad, Maiken Bratt ; Hveem, Kristian ; Vatten, Lars ; Benhamou, Simone ; Lagiou, Pagona ; Holcátová, Ivana ; Merletti, Franco ; Kjaerheim, Kristina ; Agudo, Antonio ; Castellsagué, Xavier ; Macfarlane, Tatiana V. ; Barzan, Luigi ; Canova, Cristina ; Lowry, Ray ; Conway, David I. ; Znaor, Ariana ; Healy, Claire ; Curado, Maria Paula ; Koifman, Sergio ; Eluf-Neto, Jose ; Matos, Elena ; Menezes, Ana ; Fernandez, Leticia ; Metspalu, Andres ; Heath, Simon ; Lathrop, Mark ; Brennan, Paul. / Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals. In: International Journal of Epidemiology. 2010 ; Vol. 39, No. 2. pp. 563-577.
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abstract = "Background: Genetic variants in 15q25 have been identified as potential risk markers for lung cancer (LC), but controversy exists as to whether this is a direct association, or whether the 15q variant is simply a proxy for increased exposure to tobacco carcinogens. Methods: We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies. Results: Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P20 CPD) [odds ratio (OR)=1.13, 95{\%} confidence interval (CI) 0.96-1.34, P=0.13 for heterozygotes and 1.81, 95{\%} CI 1.39-2.35 for homozygotes, P-18), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR=1.27, 95{\%} CI 1.19-1.35, P=5 × 10-13). Furthermore, we found an association between the variant allele and an earlier age of LC onset (P=0.02). The association was also noted in UADT cancers (OR=1.08, 95{\%} CI 1.01-1.15, P=0.02). Genome wide association (GWA) analysis of over 300 000 SNPs on 11 219 subjects did not identify any additional variants related to smoking behaviour. Conclusions This study confirms the strong association between 15q gene variants and LC and shows an independent association with smoking quantity, as well as an association with UADT cancers.",
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T1 - Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals

AU - Lips, Esther H.

AU - Gaborieau, Valerie

AU - McKay, James D.

AU - Chabrier, Amelie

AU - Hung, Rayjean J.

AU - Boffetta, Paolo

AU - Hashibe, Mia

AU - Zaridze, David

AU - Szeszenia-Dabrowska, Neonilia

AU - Lissowska, Jolanta

AU - Rudnai, P.

AU - Fabianova, Eleonora

AU - Mates, Dana

AU - Bencko, Vladimir

AU - Foretova, Lenka

AU - Janout, Vladimir

AU - Field, John K.

AU - Liloglou, Triantafillos

AU - Xinarianos, George

AU - McLaughlin, John

AU - Liu, Geoffrey

AU - Skorpen, Frank

AU - Elvestad, Maiken Bratt

AU - Hveem, Kristian

AU - Vatten, Lars

AU - Benhamou, Simone

AU - Lagiou, Pagona

AU - Holcátová, Ivana

AU - Merletti, Franco

AU - Kjaerheim, Kristina

AU - Agudo, Antonio

AU - Castellsagué, Xavier

AU - Macfarlane, Tatiana V.

AU - Barzan, Luigi

AU - Canova, Cristina

AU - Lowry, Ray

AU - Conway, David I.

AU - Znaor, Ariana

AU - Healy, Claire

AU - Curado, Maria Paula

AU - Koifman, Sergio

AU - Eluf-Neto, Jose

AU - Matos, Elena

AU - Menezes, Ana

AU - Fernandez, Leticia

AU - Metspalu, Andres

AU - Heath, Simon

AU - Lathrop, Mark

AU - Brennan, Paul

PY - 2010/4

Y1 - 2010/4

N2 - Background: Genetic variants in 15q25 have been identified as potential risk markers for lung cancer (LC), but controversy exists as to whether this is a direct association, or whether the 15q variant is simply a proxy for increased exposure to tobacco carcinogens. Methods: We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies. Results: Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P20 CPD) [odds ratio (OR)=1.13, 95% confidence interval (CI) 0.96-1.34, P=0.13 for heterozygotes and 1.81, 95% CI 1.39-2.35 for homozygotes, P-18), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR=1.27, 95% CI 1.19-1.35, P=5 × 10-13). Furthermore, we found an association between the variant allele and an earlier age of LC onset (P=0.02). The association was also noted in UADT cancers (OR=1.08, 95% CI 1.01-1.15, P=0.02). Genome wide association (GWA) analysis of over 300 000 SNPs on 11 219 subjects did not identify any additional variants related to smoking behaviour. Conclusions This study confirms the strong association between 15q gene variants and LC and shows an independent association with smoking quantity, as well as an association with UADT cancers.

AB - Background: Genetic variants in 15q25 have been identified as potential risk markers for lung cancer (LC), but controversy exists as to whether this is a direct association, or whether the 15q variant is simply a proxy for increased exposure to tobacco carcinogens. Methods: We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies. Results: Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P20 CPD) [odds ratio (OR)=1.13, 95% confidence interval (CI) 0.96-1.34, P=0.13 for heterozygotes and 1.81, 95% CI 1.39-2.35 for homozygotes, P-18), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR=1.27, 95% CI 1.19-1.35, P=5 × 10-13). Furthermore, we found an association between the variant allele and an earlier age of LC onset (P=0.02). The association was also noted in UADT cancers (OR=1.08, 95% CI 1.01-1.15, P=0.02). Genome wide association (GWA) analysis of over 300 000 SNPs on 11 219 subjects did not identify any additional variants related to smoking behaviour. Conclusions This study confirms the strong association between 15q gene variants and LC and shows an independent association with smoking quantity, as well as an association with UADT cancers.

KW - Lung cancer

KW - Nicotine dependence

KW - Smoking quantity

KW - UADT cancer

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