A V141L polymorphism of the human LRMP gene is associated with survival of lung cancer patients.
Mouse Lrmp and Casc1 genes are candidates for the pulmonary adenoma susceptibility 1 (Pas1) locus, the major determinant of strain variation in lung tumor susceptibility. These genes contain coding and non-coding single nucleotide polymorphisms (SNPs) strongly associated with lung tumor risk in mice. Analysis of LRMP and CASC1 gene SNPs in 361 lung adenocarcinoma (ADCA) patients and 327 healthy controls revealed common SNPs in LRMP (V141L and S197C) and CASC1 (R33S and three intronic variations), and none showed a significant association with lung ADCA risk. However, in the time-dependent Cox regression model, after adjustment for age, gender, smoking history and clinical stage, the carrier status of the Leu variation (V141L) of the LRMP gene was associated with higher mortality in patients with age at tumor onset < or = 65 years [hazard ratio (HR) 2.3; 95% CI 1.4-3.7; P = 0.001]. These findings suggest that the LRMP V141L polymorphism can predict survival in lung ADCA and that the role of LRMP and CASC1 in human lung cancer risk may differ from that in mice.
Manenti
Giacomo
G
Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Milan, Italy.
Galbiati
Federica
F
Pettinicchio
Angela
A
Spinola
Monica
M
Piconese
Silvia
S
Leoni
Vera Piera
VP
Conti
Barbara
B
Ravagnani
Fernando
F
Incarbone
Matteo
M
Pastorino
Ugo
U
Dragani
Tommaso A
TA
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality*; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D017386:Sequence Homology, Amino Acid; D016019:Survival Analysis
C486311:IRAG2 protein, human; D008565:Membrane Proteins