Multiple genetic loci modulate lung adenocarcinoma clinical staging.
OBJECTIVE
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.


METHODS
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)) and showed a 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.


CONCLUSIONS
These data point to the role of germ line variations involving multiple loci in modulating clinical stage and, therefore, prognosis in lung ADCA patients.
Fondazione IRCCS Istituto Nazionale Tumori, Università degli Studi di Milano, Milan, Italy.
Elisa
E
Frullanti
Antonella
A
Galvan
Felicia S
FS
Falvella
Giacomo
G
Manenti
Francesca
F
Colombo
Alberto
A
Vannelli
Matteo
M
Incarbone
Marco
M
Alloisio
Mario
M
Nosotti
Luigi
L
Santambrogio
Anna
A
Gonzalez-Neira
Ugo
U
Pastorino
Tommaso A
TA
Dragani
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods* / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D055815:Young Adult
D014408:Biomarkers, Tumor