Cystic fibrosis transmembrane conductance regulator gene mutation and lung cancer risk

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) holds an important role in retaining lung function, but its association with lung cancer is unclear. A case-control study was conducted to determine the possible associations of the genetic variants in the CFTR gene with lung cancer risk. Genotypes of the most common deletion DeltaF508, one functional SNP, and eight tag SNPs in the CFTR gene were determined in 574 lung cancer patients and 679 controls. A logistic regression model, adjusting for known risk factors, was used to evaluate the association of each variant with lung cancer risk, as confirmation haplotype and sub-haplotype analyses were performed. DeltaF508 deletion and genotypes with minor alleles in one tag SNP, rs10487372, and one functional SNP, rs213950, were inversely associated with lung cancer risk. The results of haplotype and sub-haplotype analyses were consistent with single variant analysis, all pointing to deletion DeltaF508 being the key variant for significant haplotypes and sub-haplotypes. Individuals with 'deletion-T' (DeltaF508/rs10487372) haplotype had a 68% reduced risk for lung cancer compared to common haplotype 'no-deletion-C' (OR=0.32; 95% CI=0.15-0.68; p=0.01). Genetic variations in the CFTR gene might modulate the risk of lung cancer. This study, for the first time, provides evidence of a protective role of the CFTR deletion carrier in the etiology of lung cancer.

Figure 1

LD plot of one deletion and nine SNPs of the CFTR gene in 679 Caucasian controls. The dash line indicates the relative location of ΔF508 deletion (rs332). The numbers in the boxes indicate D′ values.

Figure 2

Plot of global p values for sub-haplotypes. A, three loci haplotypes; B, two loci haplotyps; Global p values were indicated.

Figure 2

Plot of global p values for sub-haplotypes. A, three loci haplotypes; B, two loci haplotyps; Global p values were indicated.

Figure 3

Plot of p values for the sequential haplotype scan. The start locus is indicated by a filled triangle, and the other loci combined with the start locus are indicated by a circle. SNP1-9 are listed in Table 1.