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Cited by 145Smoking Behavior and CessationGenetic Associations and EpidemiologyPharmacogenetics and Drug Metabolism

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

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Lips, Esther H, Gaborieau, Valerie, McKay, James D, Chabrier, Amelie, Hung, Rayjean J, Boffetta, Paolo, Hashibe, Mia, Zaridze, David +42 more·2010·International Journal of Epidemiology
DOI 10.1093/ije/dyp288PMC PMC2913450
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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 (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 x 10(-18)), was virtually unchanged after adjusting for this smoking association (smoking adjusted OR = 1.27, 95% CI 1.19-1.35, P = 5 x 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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  • Allelic variation in the α5/α3/β4 nAChR subunit gene cluster at chromosome 15q25 significantly increases risk of tobacco addiction.

    “It has been shown that allelic variation in the α5/α3/β4 nAChR subunit gene cluster located in chromosome region 15q25 significantly increases risk of tobacco addiction (Saccone et al. 2007;Berrettini et al. 2008;Lips et al. 2010).”

    From Mechanisms of Nicotine Addiction (2021) · cites this paper as Lips et al. 2010

    The Results and Discussion report that a variant in the 15q25 receptor-gene cluster is associated with smoking more cigarettes per day and with heavy smoking. They do not establish the claimed significant increase in risk of tobacco addiction: the paper distinguishes smoking quantity from nicotine dependence, and the Results find no association with smoking initiation or cessation. Page numbers are not available in our copy. (LLM, conf=0.85)

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Authors
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., McLaughlin, J., Liu, G., Skorpen, F., Elvestad, M. B., Hveem, K., Vatten, L., Study, E., Benhamou, S., Lagiou, P., Holcátová, I., Merletti, F., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T. V., Barzan, L., Canova, C., Lowry, R., Conway, D. I., Znaor, A., Healy, C., Curado, M. P., Koifman, S., Eluf-Neto, J., Matos, E., Menezes, A., Fernandez, L., Metspalu, A., Heath, S., Lathrop, M., & Brennan, P.
Affiliations
  • Centre international de recherche sur le cancer (FR)
  • Mount Sinai Hospital (CA)
  • Russian Cancer Research Center NN Blokhin (RU)
  • The Maria Sklodowska-Curie National Research Institute of Oncology (PL)
  • University of Liverpool (GB)
  • Princess Margaret Cancer Centre (CA)
  • Norwegian University of Science and Technology (NO)
  • Inserm (FR)
  • Charles University (CZ)
  • University of Turin (IT)
  • Institut d'Investigació Biomédica de Bellvitge (ES)
  • University of Aberdeen (GB)
  • Azienda Ospedaliera Santa Maria Degli Angeli (IT)
  • University of Padua (IT)
  • Newcastle University (GB)
  • University of Glasgow (GB)
  • Hrvatski zavod za javno zdravstvo (HR)
  • Trinity College Dublin (IE)
  • Universidad de Buenos Aires (AR)
  • Universidade Federal de Pelotas (BR)
  • Estonian Biocentre (EE)
  • Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
Corresponding author
Brennan, Paul
ORCID
Venue
International Journal of Epidemiology
Publisher
Oxford University Press (OUP)
Published
2009-09-23
Volume
39
Issue
2
Pages
563-577
ISSN
  • 0300-5771 (ISSN-L)
  • 1464-3685
DOI
10.1093/ije/dyp288
PMC
PMC2913450
OpenAlex
W2137667379
Cited by
145
References
3
Citations by year
2025: 1 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 11 · 2019: 7 · 2018: 4 · 2017: 2 · 2016: 9 · 2015: 16 · 2014: 12 · 2013: 12 · 2012: 21
FWCI
11.97
Type
journal article
Language
en
Open access
Locations
  • International Journal of Epidemiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
  • Edge Hill University Research Information Repository (Edge Hill University) (submittedVersion)
  • Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • National Institutes of Health (5r03ca133939-02)
  • National Cancer Institute (R03 CA133939-01, R01CA092039)
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
rs16969968, single nucleotide polymorphisms, lung cancer, upper aerodigestive tract cancer, smoking quantity, tobacco use, genetic susceptibility, age at cancer onset, genome-wide association study, gene-environment interaction, cancer risk biomarkers, tobacco-related cancer
MeSH terms
Aged, Chromosomes, Human, Pair 15, Female, Genotype, Humans, Lung Neoplasms, Male, Middle Aged, Receptors, Nicotinic, Smoking, Tobacco Use Disorder, Odds Ratio, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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