Association of the FAM46A Gene VNTRs and BAG6 rs3117582 SNP with Non Small Cell Lung Cancer (NSCLC) in Croatian and Norwegian Populations

Abstract

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.

RIG-I activation induces the release of extracellular vesicles with antitumor activity

“…A critical role of BAG6-positive EVs for tumor rejection and NKp30-dependent NK cell activation was previously reported 7,11 and gene variations in the BAG6 gene are associated with lung cancer 46,47 and colon cancer 48 …”

Six genes as potential diagnosis and prognosis biomarkers for hepatocellular carcinoma through data mining

“…For examples, some research have reported that BCL2‐associated athanogene 6 (BAG6) gene is located on chromosome 6p21.3 and regulates gene expression, cell apoptosis, human leukocyte antigen (HLA) class II expression, T‐cell responses and protein modification and so forth and also demonstrated the single‐nucleotide polymorphisms (SNPs) in BAG6 gene (rs1052486 and rs3117582) is associated with lung cancer (Y. Wang et al, ). Besides, BAG6 rs3117582 SNP is associated with nonsmall cell lung cancer in both the Croatian and Norwegian populations (Etokebe et al, ). This study suggested these loci could be potential research targets and therapeutic potentials.…”

Structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by TRC35

“…The most likely explanation is that cells regulate Bag6 localization by modulating Bag6 levels or decreasing TRC35 levels. In humans, the Bag6 rs3117582 single nucleotide polymorphism found in the promoter region of Bag6 likely affects expression levels and is associated with higher incidence of lung cancer (38)(39)(40) and osteoarthritis (41). The localization could also be pretranslationally regulated with differential splicing.…”