Genetic susceptibility to tuberculosis includes several unknown yet different loci each contributing to a small extent. Intronic polymorphisms within the interferon-g (IFN-g) gene IFNG Tþ874A and IFNG Gþ2109A correlate with the IFN-g production in vitro, and the frequency of potential high IFN-g producers was previously reported by others to be lower in patients than in controls from Sicily. The aim of this study was to determine whether there is an association between polymorphisms in the IFN-g gene and predisposition to tuberculosis. We analysed two IFNG SNPs (Tþ874A and Gþ2109A) in patients (n ¼ 253) hospitalized in Rijeka (Croatia) and controls (n ¼ 519) from the same area. Onefifth of the controls were healthy contacts of the diseased, and the rest were blood donors. IFNG alleles, their predicted haplotypes or genotypes were not associated with disease susceptibility. Thus, we could not reproduce results from Sicilian case-control study. However, T/Tþ874 (possible high IFN-g producer) and þ874A/A (putative low producer) genotypes were associated with microscopically positive-negative forms of disease. Haplotypes (Tþ874A and Gþ2109A) based on a prediction by software PHASE and subsequent genotype analysis corroborated these findings. Patients had significantly higher frequency of genotypes without T at þ874 (AA/AA; AA/AG and AG/AG) in microscopyor bacterial culture-positive groups compared with their negative counterparts. These data suggest an association with disease severity rather than susceptibility to tuberculosis in Croatian Caucasian population.

Lung cancer is one of the most common malignant diseases and is amongst the leading causes of death. Cell-mediated immune response and cytokines could play an important role in antitumour immunity. The aim of the study was to evaluate the cytokines', tumour necrosis factor-a (TNF-a), interleukin-1b (IL-1b) and IL-6, releasing capacity in patients with lung carcinoma and benign lung disease. A group of 41 patients were tested for the production of TNF-a, IL-1b and IL-6 in bronchoalveolar lavage (BAL) and blood. The levels of cytokines in the lung cancer patients were: (1) in BAL ± IL-6, 173 AE 85 pg/ml; TNF-a, 170 AE 116 pg/ml; and IL-1b, 473 AE 440 pg/ml; (2) in the blood ± IL-6, 197 AE 53 pg/ml; TNF-a, 311 AE 202 pg/ml; and IL-1b, 915 AE 239 pg/ml. Alveolar macrophages of the patients with a lung cancer secreted significantly more cytokines, IL-6 (P 0.0004) and IL-1b (P 0.0047), than alveolar macrophages of the patients with a nonmalignant lung cancer. However, significantly lower levels of cytokine production by the BAL cells were found in patients with small cell lung cancer. This production decreased further in phase IV of nonsmall cell lung cancer.

We analyzed for associations between a variable number of tandem repeat (VNTR) polymorphism in the Family with sequence similarity 46, member A (FAM46A) gene and a single nucleotide polymorphism (rs3117582) in the BCL2-Associated Athanogene 6 (BAG6) with non small cell lung cancer in Croatian and Norwegian subjects. A total of 503 (262 Croatian and 241Norwegian) non small cell lung cancer patients and 897 controls (568 Croatian and 329 Norwegian) were analyzed. We found that the frequency of allele b (three VNTR repeats) of FAM46A gene was significantly increased in the patients compared to the healthy controls in the Croatian and the combined Croatian and Norwegian subjects. Genotype frequencies of cd (four and five VNTR repeats) and cc (four VNTR repeats homozygote) of the FAM46A gene were significantly decreased in the patients compared to the healthy controls in the Croatian and Norwegian subjects, respectively. Logistic regression analyses revealed FAM46A genotype cc to be an independent predictive factor for non small cell lung cancer risk in the Norwegian subjects after adjustment for age, gender and smoking status. This is the first study to suggest an association between the FAM46A gene VNTR polymorphisms and non small cell lung cancer. We found also that BAG6 rs3117582 SNP was associated with non small cell lung cancer in the Norwegian subjects and the combined Croatian-Norwegian subjects corroborating the earlier finding that BAG6 rs3117582 SNP was associated with lung cancer in Europeans. Logistic regression analyses revealed that genotypes and alleles of BAG6 were independent predictive factor for non small cell lung cancer risk in the Norwegian and combined Croatian-Norwegian subjects, after adjustment for age and gender.

Lung cancer is a complex disease, and many factors, including environmental and occupational exposure, cigarette smoking, and genetics, contribute to its progression. Angiotensin-converting enzyme (ACE) is an important regulator of blood pressure and cardiovascular homeostasis. Plasma levels of ACE depend on an insertion/deletion (I/D) polymorphism in its gene. Current correlation data between lung cancer and the ACE I/D polymorphism are contradictory or insufficient. We investigated whether the ACE I/D polymorphism is associated with a risk for lung cancer development in the Croatian population, representing the first report in a population of Slavic origin. A total of 308 lung cancer patients and 353 control subjects were genotyped for the ACE I/D polymorphism by polymerase chain reaction. The observed distribution of genotypes and alleles showed no significant difference between total patients and controls (p>0.050). However, in a subgroup of nonsmall cell lung cancer patients with squamous cell carcinoma, a significantly higher frequency of the DD genotype (37.7% vs. 27.8%, p=0.030, OR=1.57, 95% CI=1.05-2.36) and D allele was observed compared with the control group (61.3% vs. 52.8%, p=0.015, OR=1.41, 95% CI=1.07-1.87). The DD genotype of ACE may contribute to a higher risk of developing squamous cell carcinoma in the Croatian population.