Frullanti E, Galvan A, Falvella FS, Manenti G, Colombo F, Vannelli A, Incarbone M, Alloisio M, Nosotti M, Santambrogio L, Gonzalez-Neira A, Pastorino U, Dragani TA.
Dept. of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori.
Abstract
PURPOSE: The main prognostic factor of lung cancer patients' 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 600-K 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, three 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 ~20% of the phenotypic variation in clinical staging (P <2 x 10-16) and showed a statistically significant difference in overall survival (P = 8.0 x 10-8). The strongest statistical association was observed at rs10278557 (P = 1.1 x 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.