Multiple genetic loci modulate lung adenocarcinoma clinical staging

Elisa Frullanti, Antonella Galvan, Felicia S. Falvella, Giacomo Manenti, Francesca Colombo, Alberto Vannelli, Matteo Incarbone, Marco Alloisio, Mario Nosotti, Luigi Santambrogio, Anna Gonzalez-Neira, Ugo Pastorino, Tommaso A. Dragani

Research output: Contribution to journalArticle

Abstract

Purpose: The main prognostic factor of lung cancer patient outcome is clinical stage, a parameter of tumor aggressiveness. Our study was conducted to test whether germ line variations modulate individual differences in clinical stage. Experimental Design: We conducted a case-only genome-wide association study (GWAS) using a 620,901 single-nucleotide polymorphism (SNP) array in a first series of 600 lung adenocarcinoma (ADCA) patients and in a replication series of 317 lung ADCA patients. Results: GWAS identified 54 putatively associated SNPs, 3 of which were confirmed in the replication series. Joint analysis of the two series pointed to 22 statistically associated (P <0.01) genetic variants that together explained about 20% of the phenotypic variation in clinical staging (P-16) andshoweda statistically significant difference in overall survival (P = 8.0 × 10-8). The strongest statistical association was observed at rs10278557 (P = 1.1 × 10-5), located in the mesenchyme homeobox 2 (MEOX2) gene. Conclusion: These data point to the role of germ line variations involving multiple loci in modulating clinical stage and, therefore, prognosis in lung ADCA patients.

Original languageEnglish
Pages (from-to)2410-2416
Number of pages7
JournalClinical Cancer Research
Volume17
Issue number8
DOIs
Publication statusPublished - Apr 15 2011

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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