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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.

Chest wall tumors have long represented challenging clinical entities for surgeons. Until recently, incorrect diagnosis, incomplete resection, or inability to perform successful reconstruction of large thoracic wall defects led to high rates of perioperative morbidity and mortality. The latter were primarily associated with infections of the pleural cavity, respiratory failure, and paradoxical breathing. The long-term prognosis was also poor owing to a high percentage of local relapse. During the same operating procedure wide resection and reconstruction of the thoracic wall are performed successfully. Improvement of the prognosis reported in large series of patients with resection leads to surgical treatment being considered the best option for primary tumors and for selected secondary tumors of the chest wall. Because positive margins are the most important risk factor for local recurrence, adequate margins of healthy tissue surrounding the tumors have a considerable impact on disease-free and overall survival. Involvement of ribs, sternum, superior sulcus, or spine is not considered a technical limitation to surgical resection. Nowadays correct management cannot be precluded by tumor size, site, or contiguous structure involvement because concurrent reconstruction with prosthetic materials and myocutaneous flaps is feasible. Surgery provides the best chance of cure in patients with chest wall tumors. Therefore the surgical strategy must be based on the features of the individual’s disease.

The prognostic values of loss of heterozygosity (LOH) at loci frequently involved in non-small cell lung cancer and of KRAS2 gene mutations were studied in lung adenocarcinoma patients. LOHs were relatively common, ranging from 24% at chromosome 10p to 55% at chromosome 17p13. KRAS2 mutations at codon 12 were present in 26% of cases, were more common in male than in female patients and were associated with a smoking habit. No association between LOH at any site and clinical stage or survival rate was found. On the other hand, we observed a trend between the presence of any type of KRAS2 mutations and poor survival. Analysis of specific KRAS2 mutations showed a strong effect of Asp (GAT) and Val (GTT) mutations, resulting in a very poor survival compared with wild type group, whereas the most common mutation (Cys, TGT) was not associated with prognosis. Our results indicate the importance of specific activating mutations of the KRAS2 gene as genetic markers of clinical outcome for patients with lung adenocarcinoma. Int. J. Cancer (Pred. Oncol.) 79:269–272, 1998.© 1998 Wiley-Liss, Inc.

Italian and Japanese non-small-cell lung-cancer patients were genotyped for an intragenic L-myc EcoRI restriction site polymorphism previously reported to be associated with lung-tumor prognosis in Asian populations but not in Caucasians. Screening of the L-myc sequence in Italian samples allowed identification of 2 additional 3'-UTR SNPs, located 2.3–3.0 kb from the EcoRI polymorphism, but no coding polymorphism was found. No significant association was found between any of the 3 SNPs and lung-tumor prognosis in Italian patients, consistent with the reported difference between Caucasian and Asian populations. Moreover, the newly discovered polymorphisms in the Italian group were not present in Japanese patients. Significant LD between EcoRI and the 2 other SNPs was detected in the Italian population, whereas no significant LD between the 2 3'-UTR markers was detected despite their close proximity (0.7 kb). Thus, the disparate conclusions about the role of L-myc polymorphism in tumor prognosis among different populations may rest in population-specific LD between the functional gene and the L-myc polymorphism. © 2001 Wiley-Liss, Inc.