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; Peter Rudnai; Eleonora Fabianova; Dana Mates; Vladimir Bencko; Lenka Foretova; Vladimir Janout; John K. Field; Triantafillos Liloglou; George Xinarianos; John McLaughlin; Geoffrey 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

doi:10.1093/ije/dyp288

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
, Peter Rudnai
, Eleonora Fabianova
, Dana Mates
, Vladimir Bencko
, Lenka Foretova
, Vladimir Janout
, John K. Field
, Triantafillos Liloglou
, George Xinarianos
, John McLaughlin

Geoffrey 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

Family , Population and Preventative Medicine

International Agency for Research on Cancer
University of Toronto
Blokhin Cancer Research Center
Nofer Institute of Occupational Medicine
Maria Sklodowska-Curie Institute of Oncology
Johan National Institute of Public Health
Regional Authority of Public Health
National Institute of Public Health
Charles University
Masaryk Memorial Cancer Institute
Palacký University Olomouc
University of Liverpool
Cancer Care Ontario
Princess Margaret Cancer Centre
Norwegian University of Science and Technology
Institut national de la santé et de la recherche médicale
University of Paris Sud
National and Kapodistrian University of Athens
University of Turin
Cancer Registry of Norway Institute of Population-Based Cancer Research
Institut Catala' d'Oncologia (ICO)-IDIBELL
CIBER Epidemiología y Salud Pública (CIBERESP)
University of Aberdeen
General Hospital
University of Padua
Newcastle University
University of Glasgow
Croatian National Institute of Public Health
Trinity College Dublin
Hospital Araujo Jorge
Fundação Oswaldo Cruz
Universidade de São Paulo
Universidad de Buenos Aires
Universidade Federal de Pelotas
National School of Public Health
University of Tartu
Institut Génomique, Commissariat À l'Énergie Atomique
Fondation Jean Dausset - CEPH

Research output: Contribution to journal › Article › peer-review

115 Scopus citations

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 (P<0.001). The variant was associated with heavy smoking (>20 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<0.0001]. The strong association between the variant and LC risk (OR=1.30, 95% CI 1.23-1.38, P = 1 × 10^-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 language	English
Article number	dyp288
Pages (from-to)	563-577
Number of pages	15
Journal	International Journal of Epidemiology
Volume	39
Issue number	2
DOIs	https://doi.org/10.1093/ije/dyp288
State	Published - Apr 2010

Keywords

Lung cancer
Nicotine dependence
Smoking quantity
UADT cancer

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10.1093/ije/dyp288

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Lips, E. H., Gaborieau, V., McKay, J. D., Chabrier, A., Hung, R. J., Boffetta, P., Hashibe, M., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Bencko, V., Foretova, L., Janout, V., Field, J. K., Liloglou, T., Xinarianos, G., ... 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. Article dyp288. https://doi.org/10.1093/ije/dyp288

@article{ee704d2460604c66b7def8ce531068a2,

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

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 (P<0.001). The variant was associated with heavy smoking (>20 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<0.0001]. The strong association between the variant and LC risk (OR=1.30, 95\% CI 1.23-1.38, P = 1 × 10-18), 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.",

keywords = "Lung cancer, Nicotine dependence, Smoking quantity, UADT cancer",

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

year = "2010",

month = apr,

doi = "10.1093/ije/dyp288",

language = "English",

volume = "39",

pages = "563--577",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

number = "2",

}

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

TY - JOUR

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, Peter

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 (P<0.001). The variant was associated with heavy smoking (>20 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<0.0001]. The strong association between the variant and LC risk (OR=1.30, 95% CI 1.23-1.38, P = 1 × 10-18), 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 (P<0.001). The variant was associated with heavy smoking (>20 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<0.0001]. The strong association between the variant and LC risk (OR=1.30, 95% CI 1.23-1.38, P = 1 × 10-18), 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

UR - https://www.scopus.com/pages/publications/77951766653

U2 - 10.1093/ije/dyp288

DO - 10.1093/ije/dyp288

M3 - Article

C2 - 19776245

AN - SCOPUS:77951766653

SN - 0300-5771

VL - 39

SP - 563

EP - 577

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 2

M1 - dyp288

ER -

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

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