Adenosine triphosphate-binding cassette B1 (ABCB1) (multidrug resistance 1) G2677T/A gene polymorphism is associated with high risk of lung cancer.
BACKGROUND
P-glycoprotein (P-gp) is a transmembrane transporter that is encoded by the adenosine triphosphate-binding cassette B1 (ABCB1) (multidrug resistance 1) gene, which plays a role in cell defense against environmental attacks, like those generated by xenobiotics. P-gp is expressed in the lung, where it has been suggested to transport these compounds from the interstitium into the lumen.


METHODS
Two functional ABCB1 polymorphisms were examined, G2677T/A (in exon 21) and C3435T (in exon 26), in a group of lung cancer patients and in a control group.


RESULTS
Whereas 3435T allelic and genotype frequencies were unchanged between both study groups, lung cancer patients showed higher frequency of the 2677T variant allele compared with the control group (0.67 vs. 0.43; P < .001; odds ratio, [OR], 2.6; 95% confidence interval [95% CI], 1.7-4.0). Among the histologic tumor types that were included in the study, squamous cell carcinoma was associated most strongly with the presence of the 2677T allele (OR, 3.92; 95% CI, 2.2-6.9) and especially was associated with the 2677 TT genotype (OR, 6.75; 95% CI, 3.0-15.2). In a haplotype analysis, homozygous wild-type alleles were classified as genotype A, heterozygous alleles were classified as genotype B, and homozygous mutant allele were classified as genotype C both in exon 21 (first letter) and in exon 26 (second letter) loci. The haplotype CB displayed the highest association with lung cancer (OR, 18.09; 95% CI, 2.4-139.2).


CONCLUSIONS
The current results taken together suggest that, aside from other known causes of lung cancer, such as tobacco smoke, the existence of polymorphisms in the ABCB1 gene and, specifically, the presence of the G2677T mutation can be crucial in conferring susceptibility to lung cancer. Further studies comprising larger populations are needed to confirm these preliminary findings.
Gervasini
Guillermo
G
Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain. ggervasi@unex.es
Carrillo
Juan Antonio
JA
Garcia
Montserrat
M
San Jose
Carmen
C
Cabanillas
Agustin
A
Benitez
Julio
J
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027361:Organic Anion Transporters