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1.  A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker 
Pregnane X receptor (PXR) is an important member of the nuclear receptor superfamily that copes with various endobiotic and xenobiotic stimuli, such as carcinogens by regulating an array of environmental response genes. Low PXR expression has been shown to promote tumor initiation and metastasis. The aim of the current study was to investigate whether the single nucleotide polymorphisms (SNPs) of PXR could alter lung cancer susceptibility in Chinese by affecting the function or expression of PXR. We genotyped three putatively functional SNPs of PXR (i.e., rs3814055C>T, rs3732360C>T, and rs3814058C>T) and analyzed their associations with lung cancer risk in a two-stage case-control study with a total of 1559 lung cancer cases and 1679 controls in the southern and eastern Chinese population. We found that in comparison to the rs3814058CC common genotype, the rs3814058T variants (TC/TT) which is located in the 3'-untranslated region (3'-UTR) of PXR conferred a consistently increased risk of lung cancer in both the southern Chinese (odd ratios (OR) = 1.24, 95% confidence interval (CI) = 1.03−1.49) and the eastern Chinese (OR = 1.33, 95% CI = 1.02−1.75). The variants also significantly interacted with smoking on increasing cancer risk (p = 0.023). Moreover, lung cancer tissues with the rs3814058T variants showed significantly lower PXR expression than those with rs3814058CC genotype in the smokers (p = 0.041). These results suggested that the rs3814058C>T polymorphism of PXR interacts with smoking on increasing lung cancer risk in Chinese smokers, which might be a functional genetic biomarker for lung cancer.
PMCID: PMC4227172  PMID: 25268617
pregnane X receptor (PXR); lung cancer; susceptibility
2.  Functional Polymorphisms of CHRNA3 Predict Risks of Chronic Obstructive Pulmonary Disease and Lung Cancer in Chinese 
PLoS ONE  2012;7(10):e46071.
Recently, several genome-wide association studies (GWAS) have identified many susceptible single nucleotide polymorphisms (SNPs) for chronic obstructive pulmonary disease (COPD) and lung cancer which are two closely related diseases. Among those SNPs, some of them are shared by both the diseases, reflecting there is possible genetic similarity between the diseases. Here we tested the hypothesis that whether those shared SNPs are common predictor for risks or prognosis of COPD and lung cancer. Two SNPs (rs6495309 and rs1051730) located in nicotinic acetylcholine receptor alpha 3 (CHRNA3) gene were genotyped in 1511 patients with COPD, 1559 lung cancer cases and 1677 controls in southern and eastern Chinese populations. We found that the rs6495309CC and rs6495309CT/CC variant genotypes were associated with increased risks of COPD (OR = 1.32, 95% C.I. = 1.14–1.54) and lung cancer (OR = 1.57; 95% CI = 1.31–1.87), respectively. The rs6495309CC genotype contributed to more rapid decline of annual Forced expiratory volume in one second (FEV1) in both COPD cases and controls (P<0.05), and it was associated with advanced stages of COPD (P = 0.033); the rs6495309CT/CC genotypes conferred a poor survival for lung cancer (HR = 1.41, 95%CI = 1.13–1.75). The luciferase assays further showed that nicotine and other tobacco chemicals had diverse effects on the luciferase activity of the rs6495309C or T alleles. However, none of these effects were found for another SNP, rs1051730G>A. The data show a statistical association and suggest biological plausibility that the rs6495309T>C polymorphism contributed to increased risks and poor prognosis of both COPD and lung cancer.
PMCID: PMC3463594  PMID: 23056235

Results 1-2 (2)