A V141L polymorphism of the human LRMP gene is associated with survival of lung cancer patients

• Published in: Carcinogenesis (New York) Vol. 27; no. 7; pp. 1386 - 1390
• Main Authors: Manenti, Giacomo, Galbiati, Federica, Pettinicchio, Angela, Spinola, Monica, Piconese, Silvia, Leoni, Vera Piera, Conti, Barbara, Ravagnani, Fernando, Incarbone, Matteo, Pastorino, Ugo, Dragani, Tommaso A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2006; Oxford Publishing Limited (England)
• Subjects: ADCA; adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - mortality; allele-specific oligonucleotide; Amino Acid Sequence; Animals; ASO; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; confidence interval; Female; Genetic Predisposition to Disease; hazard ratio; Humans; linkage disequilibrium; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Medical sciences; Membrane Proteins - genetics; Mice; Molecular Sequence Data; odds ratio; Pas1; PCR; Pneumology; polymerase chain reaction; Polymorphism, Single Nucleotide; pulmonary adenoma susceptibility 1; Sequence Homology, Amino Acid; single nucleotide polymorphism; SNP; Survival Analysis; Tumors; Tumors of the respiratory system and mediastinum; Human; Lung disease; Genetic variability; Respiratory disease; Lung cancer; Genotype; Malignant tumor; Survival; Bronchopulmonary; Gene; Bronchus disease; Genetics; Polymorphism
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgi332

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 ≤ 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.