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<2 × 10-16) 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. © 2011 AACR.
Frullanti, E., Galvan, A., Falvella, F.S., Manenti, G., Colombo, F., Vannelli, A., et al. (2011). Multiple genetic loci modulate lung adenocarcinoma clinical staging. CLINICAL CANCER RESEARCH, 17(8), 2410-2416 [10.1158/1078-0432.CCR-10-2394].
Multiple genetic loci modulate lung adenocarcinoma clinical staging
FRULLANTI, ELISA;SANTAMBROGIO, LUIGI;
2011-01-01
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<2 × 10-16) 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. © 2011 AACR.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/1006645
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