Title : Genetics of endoplasmic reticulum aminopeptidases in non-small cell lung cancer - differences between smokers and never-smokers
Abstract:
Immune eradication of cancer cells is dependent on polymorphisms of HLA class I molecules and antigen-processing machinery (APM) components, of which endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2) are most genetically polymorphic. We compared the distribution of ERAP1 and ERAP2 single nucleotide polymorphisms (SNPs) in Polish patients with non-small cel lung cancer (NSCLC) and controls, stratified according to their smoking status. We found significant but opposite associations in never-smokers and in smokers of all tested SNPs (rs26653, rs2287987, rs30187, and rs27044) but one (rs26618) in ERAP1. No significant associations were seen in ERAP2. Haplotype analysis indicated that the distribution of many ERAP1/2 haplotypes is opposite, depending on smoking status. Additionally, haplotypic combination of low activity ERAP1 and the lack of an active form of ERAP2 seems to favor the disease in never-smokers. We also revealed interesting associations of some ERAP1 polymorphisms with: age at diagnosis (rs26653), disease stage (rs27044), overall survival (rs30187), and response to chemotherapy (rs27044). The results presented here may suggest the important role for ERAP1 in the anti-cancer response, which is different in smokers versus never-smokers, depending to some extent on the presence of ERAP2, and affecting NSCLC clinical course.