BACKGROUND: Lung cancer is the most common second primary cancer. We investigated whether the TNF-alpha-308 and TNF-alpha-238 polymorphisms were associated with the susceptibility and severity of lung cancer as the second primary cancer (LC2).

MATERIAL AND METHODS: This study included 104 patients from the group LC2. The control subjects included 2 groups. The first control group (LC1) comprised 201 unrelated patients with lung cancer as a first primary cancer. The second control group (HC) comprised 230 healthy blood donors, matched for sex and age to the study group.

RESULTS: The frequencies of the TNF-alpha-238 polymorphism GG genotype and the G allele were higher in the LC2 group than in the LC1 group, but the differences did not reach significance (p=0.054 and p=0.057, respectively). Similar differences were found in the TNF-alpha-238 polymorphism GG genotype and G allele between the LC2 group and the HC group (p=0.054 and p=0.057, respectively). In terms of the different types of lung cancer, patients with a second primary NSCLC (non-small cell lung cancer) more frequently had TNF-alpha-238 polymorphism GG genotypes and G alleles than patients with a first primary NSCLC (the differences approached statistical significance: p=0.060, p=0.064, respectively). All (100%) patients of group LC2 (n=104) had the GG genotype and the G allele. GG genotype was exclusive and no A allele was found in group LC2.

CONCLUSIONS: TNF-alpha-238 polymorphism GG genotype and the G allele could have a promotional effect on the development of NSCLC in the group of patients with LC2.

Keywords: Carcinoma, Non-Small-Cell Lung - genetics, Aged, 80 and over, Croatia, Gene Frequency, Genetic Predisposition to Disease - genetics, Lung Neoplasms - genetics, Neoplasms, Second Primary - genetics, Odds Ratio, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymorphism, Single Nucleotide - genetics, Promoter Regions, Genetic - genetics, Tumor Necrosis Factor-alpha - genetics