Skip to main content
SpringerLink
Log in

Chromosome 15q24-25.1 variants, diet, and lung cancer susceptibility in cigarette smokers

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Background

Studying gene–environment interactions may provide insight about mechanisms underpinning the reported association between chromosome 15q24-25.1 variation and lung cancer susceptibility.

Methods

In a nested case–control study comparing 746 lung cancer cases to 1,477 controls, all of whom were non-Hispanic white smokers in the β-Carotene and Retinol Efficacy Trial, we examined whether lung cancer risk is associated with single nucleotide polymorphisms (SNPs) tagging the AGPHD1, CHRNA5, CHRNA3, and CHRNB4 genes and whether such risk is modified by diet and other characteristics. Intake of fruits and vegetables, their botanical groups, and specific nutrients were ascertained generally at baseline by food-frequency questionnaire.

Results

Several sets of SNPs in high linkage disequilibrium were found: one set associated with a 27–34% increase and two sets associated with a 13–19% decrease in risk per minor allele. Associations were most prominent for the set including the non-synonymous SNP rs16969968. The rs16969968-lung cancer association did not differ by intake level of most dietary factors examined, but was stronger for individuals diagnosed at <70 years of age or having a baseline smoking history of <40 cigarette pack-years.

Conclusions

Our data suggests that diet has little influence on the relation between chromosome 15q24-25.1 variation and lung cancer risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AGPHD1:

Aminoglycoside phosphotransferase domain containing 1

CARET:

β-Carotene and Retinol Efficacy Trial

CHRNA5:

Cholinergic receptor, nicotinic, alpha 5

CHRNA3:

Cholinergic receptor, nicotinic, alpha 3

CHRNB4:

Cholinergic receptor, nicotinic, beta 4

CI:

Confidence interval

FFQ:

Food-frequency questionnaire

IREB2:

Iron-responsive element binding protein 2

LD:

Linkage disequilibrium

nAChR:

Nicotinic acetylcholine receptor

PFA:

Polyunsaturated fatty acid

PSMA4:

Proteasome subunit, alpha type 4

OR:

Odds ratio

SNP:

Single nucleotide polymorphism

References

  1. Bierut LJ, Madden PA, Breslau N et al (2007) Novel genes identified in a high-density genome wide association study for nicotine dependence. Hum Mol Genet 16:24–35

    Article  CAS  PubMed  Google Scholar 

  2. Hung RJ, McKay JD, Gaborieau V et al (2008) A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452:633–637

    Article  CAS  PubMed  Google Scholar 

  3. Amos CI, Wu X, Broderick P et al (2008) Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40:616–622

    Article  CAS  PubMed  Google Scholar 

  4. Thorgeirsson TE, Geller F, Sulem P et al (2008) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452:638–642

    Article  CAS  PubMed  Google Scholar 

  5. Liu P, Vikis HG, Wang D et al (2008) Familial aggregation of common sequence variants on 15q24–25.1 in lung cancer. J Natl Cancer Inst 100:1326–1330

    Article  CAS  PubMed  Google Scholar 

  6. Schuller HM (2009) Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer 195–205

  7. Schuller HM, Orloff M (1998) Tobacco-specific carcinogenic nitrosamines. Ligands for nicotinic acetylcholine receptors in human lung cancer cells. Biochem Pharmacol 55:1377–1384

    Article  CAS  PubMed  Google Scholar 

  8. Spitz MR, Amos CI, Dong Q, Lin J, Wu X (2008) The CHRNA5–A3 region on chromosome 15q24–25.1 is a risk factor both for nicotine dependence and for lung cancer. J Natl Cancer Inst 100:1552–1556

    Article  CAS  PubMed  Google Scholar 

  9. Lips EH, Gaborieau V, McKay JD et al (2010) Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17,000 individuals. Int J Epidemiol 39:563–577

    Article  PubMed  Google Scholar 

  10. Wang Y, Broderick P, Matakidou A, Eisen T, Houlston RS (2010) Role of 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never-smokers. Carcinogenesis 31:234–238

    Article  PubMed  Google Scholar 

  11. Truong T, Hung RJ, Amos CI et al (2010) Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium. J Natl Cancer Inst 102:959–971

    Article  CAS  PubMed  Google Scholar 

  12. Vainio H, Weiderpass E (2006) Fruit and vegetables in cancer prevention. Nutr Cancer 54:111–142

    Article  CAS  PubMed  Google Scholar 

  13. Buchner FL, Bueno-de-Mesquita HB, Ros MM et al (2010) Variety in fruit and vegetable consumption and the risk of lung cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 19:2278–2286

    Article  PubMed  Google Scholar 

  14. Thornquist MD, Omenn GS, Goodman GE et al (1993) Statistical design and monitoring of the Carotene and Retinol Efficacy Trial (CARET). Control Clin Trials 14:308–324

    Article  CAS  PubMed  Google Scholar 

  15. Omenn GS, Goodman GE, Thornquist MD et al (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334:1150–1155

    Article  CAS  PubMed  Google Scholar 

  16. Omenn GS, Goodman GE, Thornquist MD et al (1996) Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst 88:1550–1559

    Article  CAS  PubMed  Google Scholar 

  17. Goodman GE, Thornquist MD, Balmes J et al (2004) The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst 96:1743–1750

    Article  CAS  PubMed  Google Scholar 

  18. Neuhouser ML, Patterson RE, Thornquist MD, Omenn GS, King IB, Goodman GE (2003) Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET). Cancer Epidemiol Biomarkers Prev 12:350–358

    CAS  PubMed  Google Scholar 

  19. Schakel SF, Buzzard IM, Gebhardt SE (1997) Procedures for estimating nutrient values for food composition databases. J Food Comp Anal 10:102–114

    Article  CAS  Google Scholar 

  20. Holden JM, Eldridge AL, Beecher GR et al (1999) Carotenoid content of U.S. foods: an update of the database. J Food Comp Anal 12:169–196

    Article  CAS  Google Scholar 

  21. Carlson CS, Eberle MA, Rieder MJ, Yi Q, Kruglyak L, Nickerson DA (2004) Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am J Hum Genet 74:106–120

    Article  CAS  PubMed  Google Scholar 

  22. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265

    Article  CAS  PubMed  Google Scholar 

  23. Stephens M, Donnelly P (2003) A comparison of Bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 73:1162–1169

    Article  CAS  PubMed  Google Scholar 

  24. Broderick P, Wang Y, Vijayakrishnan J et al (2009) Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study. Cancer Res 69:6633–6641

    Article  CAS  PubMed  Google Scholar 

  25. Schwartz AG, Cote ML, Wenzlaff AS, Land S, Amos CI (2009) Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer. J Thoracic Oncol 4:1195–1201

    Article  Google Scholar 

  26. Yang P, Li Y, Jiang R, Cunningham JM, Zhang F, de Andrade M (2010) A rigorous and comprehensive validation: common genetic variations and lung cancer. Cancer Epidemiol Biomarkers Prev 19:240–244

    Article  CAS  PubMed  Google Scholar 

  27. Wang JC, Cruchaga C, Saccone NL et al (2009) Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. Hum Mol Genet 18:3125–3135

    Article  CAS  PubMed  Google Scholar 

  28. Liu P, Yang P, Wu X et al (2010) A second genetic variant on chromosome 15q24–25.1 associates with lung cancer. Cancer Res 70:3128–3135

    Article  CAS  PubMed  Google Scholar 

  29. Bierut LJ, Stitzel JA, Wang JC et al (2008) Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry 165:1163–1171

    Article  PubMed  Google Scholar 

  30. Stevens VL, Bierut LJ, Talbot JT et al (2008) Nicotinic receptor gene variants influence susceptibility to heavy smoking. Cancer Epidemiol Biomarkers Prev 17:3517–3525

    Article  CAS  PubMed  Google Scholar 

  31. Falvella FS, Galvan A, Colombo F, Frullanti E, Pastorino U, Dragani TA (2010) Promoter polymorphisms and transcript levels of nicotinic receptor CHRNA5. J Natl Cancer Inst 102:1366–1370

    Article  CAS  PubMed  Google Scholar 

  32. Falvella FS, Galvan A, Frullanti E et al (2009) Transcription deregulation at the 15q25 locus in association with lung adenocarcinoma risk. Clin Cancer Res 15:1837–1842

    Article  CAS  PubMed  Google Scholar 

  33. Liu Y, Liu P, Wen W et al (2009) Haplotype and cell proliferation analyses of candidate lung cancer susceptibility genes on chromosome 15q24–25.1. Cancer Res 69:7844–7850

    Article  CAS  PubMed  Google Scholar 

  34. De Stefani E, Boffetta P, Deneo-Pellegrini H et al (2009) Meat intake, meat mutagens and risk of lung cancer in Uruguayan men. Cancer Causes Control 20:1635–1643

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the CARET participants, along with the CARET investigators and staff at all participating trial institutions, for their effort and contribution to this research, and also Liberto Julianto and Dema Poppa for providing technical and administrative support. This work is supported by R01 CA111703, U01 CA63673, K05 CA092002, and T32 CA009168 from the National Cancer Institute of the U.S. National Institutes of Health (NIH).

Author information

Authors and Affiliations

  1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Mailstop M4-C308, Seattle, WA, 98109-1024, USA

    Lori C. Sakoda, Jennifer A. Doherty & Noel S. Weiss

  2. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Mailstop M5-C800, Seattle, WA, 98109-1024, USA

    Melissa M. Loomis & Chu Chen

  3. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Mailstop M4-B402, Seattle, WA, 98109-1024, USA

    Marian L. Neuhouser

  4. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Mailstop M3-A306, Seattle, WA, 98109-1024, USA

    Matt J. Barnett, Mark D. Thornquist & Gary E. Goodman

  5. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA

    Lori C. Sakoda, Jennifer A. Doherty, Noel S. Weiss & Chu Chen

  6. Department of Otolaryngology: Head and Neck Surgery, School of Medicine, University of Washington, Seattle, WA, US A

    Chu Chen

Authors
  1. Lori C. Sakoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Melissa M. Loomis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jennifer A. Doherty
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marian L. Neuhouser
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matt J. Barnett
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mark D. Thornquist
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Noel S. Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gary E. Goodman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chu Chen.

Additional information

The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 98 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakoda, L.C., Loomis, M.M., Doherty, J.A. et al. Chromosome 15q24-25.1 variants, diet, and lung cancer susceptibility in cigarette smokers. Cancer Causes Control 22, 449–461 (2011). https://doi.org/10.1007/s10552-010-9716-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-010-9716-1

Keywords

Search

Navigation