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.

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). Materia...