The Interaction between Four Polymorphisms and Haplotype of ABCB1, the Risk of Non-Small Cell Lung Cancer, and the Disease Phenotype

Abstract

P-glycoprotein, product of the ABCB1 (ATP binding cassette subfamily B member 1) gene, has been reported to play an important role in multiple drug resistance during cancer therapy. However, its influence on non-small cell lung cancer (NSCLC) risk has not been clearly defined. The aim of the present study was to examine the association between clinicopathological factors and SNPs T-129C, C1236T, G2677T/A, and C3435T, as well as its haplotype, and to investigate the role of ABCB1 polymorphisms in NSCLC development. The study included 80 patients who suffered from NSCLC and underwent surgery to remove the tumour and 96 healthy controls. The tissues were genotyped by PCR-RFLP and sequencing methods, and the haplotype frequencies in both groups were estimated. The SNP C3435T was identified as a NSCLC risk factor. The presence of mutated allelic variant T ( $p=0.0103$ ) or homozygote TT ( $p=0.0099$ ) was observed significantly more often in cancer patients than in healthy controls. The two groups also demonstrated a highly significant difference in common haplotype frequency ( $p=0.01$ ). The T−129-T1236-T2677-T3435 haplotype was found to be most closely associated with NSCLC risk. Although the investigated polymorphisms were not related to demographic features, clinicopathological lung tumour characteristics, or blood morphology indices, marginally significant correlations were found with some variables: C1236T with age of disease onset ( $p=0.0410$ ); C3435T with smoking status ( $p=0.0561$ ). As the findings indicate, lung cancer and control groups demonstrate significantly different patterns of −129/1236/2677/3435 haplotype distribution; T-T-T-T haplotype contributes to NSCLC susceptibility, and this effect is probably mainly dependent on C3435T. So far, similar studies were published in other populations.