Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Qiao, Dan; Yi, Long; Liu, Hua; Xu, Zheng; Ding, Yi; Shi, Dongquan; Ni, Lubin; Song, Ninghong; Wang, Yong; Wu, Hongfei

doi:10.1016/j.jcf.2007.07.011

Cited by 25 publications

(18 citation statements)

References 37 publications

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“…The present study has investigated the possible mechanism underlying this pH change and demonstrated for the first time the involvement of CFTR in mediating prostatic HCO 3 − secretion, which may be enhanced upon bacterial infection or inflammation. Apart from demonstrating CFTR expression in rat prostatic epithelium, which is consistent with that previously found in human prostate [33], [34], [35], we have also elucidated the functional roles of CFTR in the prostate in health and disease. By measuring the rate of pHi recovery from cellular alkalization, in the presence or absence of extracellular Cl − in conjunction with the use of the cAMP agonist and CFTR inhibitor, we have demonstrated that prostatic epithelium can extrude HCO 3 − under unstimulated condition through a Cl − /HCO 3 − exchanger since removal of extracellular Cl − greatly attenuated the pHi recovery rate.…”

Section: Discussionsupporting

confidence: 87%

“…In fact, our previous studies have demonstrated the involvement of CFTR in mediating uterine and oviductal HCO 3 − secretion, which are vital to the fertilizing capacity of sperm and embryo development [30], [31], [32]. Since CFTR is also known to be expressed in the human prostate [33], [34], [35], it may also play a role in prostatic HCO 3 − secretion as well although the physiological role of CFTR in the prostate has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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A Host Defense Mechanism Involving CFTR-Mediated Bicarbonate Secretion in Bacterial Prostatitis

Xie

Tang

et al. 2010

PLoS ONE

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BackgroundProstatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated.Methodology/Principal FindingsIn this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl− and HCO3 −, in mediating prostate HCO3 − secretion and its possible role in bacterial killing. Upon Escherichia coli (E coli)-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II), along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO3 − content (>50 mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO3 − on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E coli. The relevance of the CFTR-mediated HCO3 − secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues.Conclusions/SignificanceThe CFTR and its mediated HCO3 − secretion may be up-regulated in prostatitis as a host defense mechanism.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

A Host Defense Mechanism Involving CFTR-Mediated Bicarbonate Secretion in Bacterial Prostatitis

Xie

Tang

et al. 2010

PLoS ONE

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“…Blockage of these channels can suppress the growth and proliferation of human prostate cancer cells [30, 31]. A dysfunctional CFTR may weaken the ability of cancer cells to survive by handling proliferative homeostasis and thereby strengthening their pro-apoptotic potential [9, 31]. On the other hand, it has been shown that a dysfunctional CFTR was responsible for elevated blood ATP concentrations in mice and in CF patients [8, 32].…”

Section: Discussionmentioning

confidence: 99%

“…Individuals who were CFTR mutation carriers were found to be at an increased risk for young onset of pancreatic cancer [5]. An inverse association between CF gene mutations and incidence of several cancers, such as melanoma[3, 6], breast cancer[6–8], colon cancer[6] and prostate cancer[9], was also reported. However, no studies have been reported on the association between CFTR and lung cancer risk.…”

Section: Introductionmentioning

confidence: 99%

Cystic fibrosis transmembrane conductance regulator gene mutation and lung cancer risk

Sun

et al. 2010

Lung Cancer

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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.

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“…Accordingly, the best BPSO-generated SNP barcodes listed are more protective when more SNPs are selected. Similarly, accumulating evidence showed that some SNPs were reported to protective against many types of cancers [26][27][28][29]. For example, the rs243865 (C-1306T of MMP2 gene) was found to be associated with substantial reduction in risk of breast cancer [26] although they were not focused on the SNP-SNP interactions like our study.…”

Section: The Ranks Of the Odds Ratios Indicate Lowest Risk Group For mentioning

confidence: 45%

Novel generating protective single nucleotide polymorphism barcode for breast cancer using particle swarm optimization

Yang

Chang

Cheng

et al. 2009

Cancer Epidemiology

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Cystic fibrosis transmembrane conductance regulator (CFTR) gene 5T allele may protect against prostate cancer: A case-control study in Chinese Han population

Abstract: Our results indicate that the low expression CFTR polymorphisms may contribute to a reduced risk of prostate cancer in Chinese Han population.

Cited by 25 publications

References 37 publications

A Host Defense Mechanism Involving CFTR-Mediated Bicarbonate Secretion in Bacterial Prostatitis

A Host Defense Mechanism Involving CFTR-Mediated Bicarbonate Secretion in Bacterial Prostatitis

Cystic fibrosis transmembrane conductance regulator gene mutation and lung cancer risk

Novel generating protective single nucleotide polymorphism barcode for breast cancer using particle swarm optimization

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