Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene

Monica Spinola, Vera P. Leoni, Antonella Galvan, Eberhard Korsching, Barbara Conti, Ugo Pastorino, Fernando Ravagnani, Amedeo Columbano, Vidar Skaug, Aage Haugen, Tommaso A. Dragani

Research output: Contribution to journalArticle

Abstract

A genome-wide association analysis using the Affymetrix 100K SNP array was carried out in a case-control study of lung cancer. Allele frequencies were estimated initially in DNA pools. Significant differences in allele frequency detected in the SNP array analysis were first tested in the same DNA pools by pyrosequencing and then by individual genotyping. DNA pooling analysis identified rs10508266 SNP, located ∼12.5 kb from the 5′-end of the KLF6 gene, as a marker showing significant association with lung cancer risk. Since the SNP was in significant linkage disequilibrium with the KLF6 gene region, we analyzed an Italian population of 338 lung adenocarcinoma cases and 335 controls for the possible role of the reported functional rs3750861 SNP, located 15.6 kb from the rs10508266 SNP. The rs3750861 affects expression of KLF6 splicing variants in prostate cancer and we found that its rare allele is associated with reduced lung cancer risk (odds ratio, 0.5; 95% CI, 0.3-0.8). A Norwegian replication series of 265 non small cell lung cancer cases, and 356 controls, however, did not confirm the association. In light of the reported functional involvement of the KLF6 gene in lung cancer and in other cancer types and to the functional nature of the rs3750861 SNP, our results suggest a potential involvement of KLF6 polymorphisms in lung cancer risk, although additional studies in large series are needed to confirm our findings and to elucidate the mechanism by which the KLF6 SNPs influence lung cancer risk.

Original languageEnglish
Pages (from-to)311-316
Number of pages6
JournalCancer Letters
Volume251
Issue number2
DOIs
Publication statusPublished - Jun 28 2007

Fingerprint

Single Nucleotide Polymorphism
Lung Neoplasms
Genome
Genes
Gene Frequency
DNA
Odds Ratio
Genome-Wide Association Study
Linkage Disequilibrium
Non-Small Cell Lung Carcinoma
Case-Control Studies
Prostatic Neoplasms
Alleles
Population
Neoplasms

Keywords

  • Core promoter element-binding protein (COPEB)
  • Genetic susceptibility
  • Lung cancer
  • Single-nucleotide polymorphisms

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene. / Spinola, Monica; Leoni, Vera P.; Galvan, Antonella; Korsching, Eberhard; Conti, Barbara; Pastorino, Ugo; Ravagnani, Fernando; Columbano, Amedeo; Skaug, Vidar; Haugen, Aage; Dragani, Tommaso A.

In: Cancer Letters, Vol. 251, No. 2, 28.06.2007, p. 311-316.

Research output: Contribution to journalArticle

Spinola, M, Leoni, VP, Galvan, A, Korsching, E, Conti, B, Pastorino, U, Ravagnani, F, Columbano, A, Skaug, V, Haugen, A & Dragani, TA 2007, 'Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene', Cancer Letters, vol. 251, no. 2, pp. 311-316. https://doi.org/10.1016/j.canlet.2006.11.029
Spinola, Monica ; Leoni, Vera P. ; Galvan, Antonella ; Korsching, Eberhard ; Conti, Barbara ; Pastorino, Ugo ; Ravagnani, Fernando ; Columbano, Amedeo ; Skaug, Vidar ; Haugen, Aage ; Dragani, Tommaso A. / Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene. In: Cancer Letters. 2007 ; Vol. 251, No. 2. pp. 311-316.
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AU - Pastorino, Ugo

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