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Carcinogenesis Advance Access published online on January 12, 2006
Carcinogenesis, doi:10.1093/carcin/bgi332
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received September 6, 2005
Revised December 15, 2005
Accepted December 24, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

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

Giacomo Manenti 1, Federica Galbiati 1, Angela Pettinicchio 1, Monica Spinola 1, Silvia Piconese 1, Vera Piera Leoni 1, Barbara Conti 2, Fernando Ravagnani 1, Matteo Incarbone 3, Ugo Pastorino 2, and Tommaso A. Dragani 1 *

1 Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Milan, Italy
2 Department of Thoracic Surgery, Istituto Nazionale Tumori, Milan, Italy
3 Department of Thoracic Surgery, Istituto Clinico Humanitas (ICH), Rozzano, Italy

* To whom correspondence should be addressed.
Tommaso A. Dragani, E-mail: tommaso.dragani{at}istitutotumori.mi.it


  Abstract

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 3 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 role of LRMP and CASC1 in human lung cancer risk may differ from that in mice.

Keywords: SNPs; KRAS; CASC1; LRMP; genetic susceptibility; disease models.
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