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 a most common deletion ΔF508, 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. ΔF508 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 ΔF508 being the key variant for significant haplotypes and sub-haplotypes. Individuals with ‘deletion-T’ (ΔF508/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.

Constitutive Activation of Nuclear Factor κB Contributes to Cystic Fibrosis Transmembrane Conductance Regulator Expression and Promotes Human Cervical Cancer Progression and Poor Prognosis

“…5 Dysregulation of the CFTR gene is involved in several human diseases, including cystic fibrosis (CF), in which the gene is defective. 6 Genetic variations in the CFTR gene may also influence the risk of developing a variety of cancers, 7,8 suggesting that the gene may function as a tumor suppressor or promoter, according to the type of tumor. A recent study in CF lung disease showed that CFTR dysfunction can also lead to activation of epithelial cell signaling pathways and subsequent hyperinflammatory responses mediated by nuclear factor JB (NF-JB).…”

Evaluation of serum-based cancer biomarkers: A brief review from a clinical and computational viewpoint

“…The study comprised of 385 men, reported a 92% specificity, for overall prostate cancer, in contrast to 65% for PSA [6,8,12,17,18]. After a thorough examination of the methods was performed, the assays show technical inadequacies and discrepancies.…”

“…In particular, the example in the first pitfall can be rephrased such that many protein biomarkers are not cancer specific; that is, conditions other than the disease itself, may cause a protein biomarker to be present or be at an elevated level. In addition, the levels of some protein biomarkers are not elevated in all patients with a particular cancer [18]. Therefore, the computational assessment is an important tool to validate the quality of the biomarker.…”

MARCH2 regulates autophagy by promoting CFTR ubiquitination and degradation and PIK3CA-AKT-MTOR signaling

“…Genetic variations in CFTR may be associated with increased or decreased risk for developing cancers, [44][45][46] suggesting that CFTR is a tumor suppressor or promoter, according to the type of tumor. The high level of CFTR expression is associated with tumor malignancy, progression in ovarian cancer and cervical cancer.…”