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author:("Li, chengyang")
1.  Genetic Polymorphism of Angiotensin Converting Enzyme and Risk of Coronary Restenosis after Percutaneous Transluminal Coronary Angioplasties: Evidence from 33 Cohort Studies 
PLoS ONE  2013;8(9):e75285.
Background
In the past decade, a number of cohort studies studies have been carried out to investigate the relationship between the insertion/deletion polymorphism of the gene encoding angiotensin-converting enzyme and risk of restenosis after percutaneous transluminal coronary angioplasties in patients. However, these studies have yielded contradictory results. Genetic association studies addressing this issue are frequently hampered by insufficient power. We therefore performed a meta-analysis of the published studies to clarify this inconsistency and to establish a comprehensive picture of the relationship between ACE I/D polymorphism and post-PTCA restenosis risk.
Methods
Databases including Pubmed, EMBASE, ISI Web of Science, EBSCO, Cochrane Library databases and CNKI were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The random-effects model was applied, addressing heterogeneity and publication bias.
Results
A total of 33 cohort studies involving 11,099 subjects were included. In a combined analysis, the OR for post-PTCA restenosis of the ACE DD genotype was 1.61 (95% CI: 1.27–2.04; P<10−5). In the subgroup analysis by intervention, significantly increased risks were also found in PTCA-stent and PTCA-balloon for the DD genotype of the polymorphism.
Conclusions
Our meta-analysis showed that the DD genotype of ACE I/D polymorphism was significantly associated with increased risk of restenosis, particularly for PTCA-stent.
doi:10.1371/journal.pone.0075285
PMCID: PMC3787085  PMID: 24098690
2.  Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histological subtypes and age at diagnosis 
Clinical Cancer Research  2012;18(7):1947-1953.
Purpose
Our previous study revealed that 90% (47 of 52; 95% CI: 0.79–0.96) of Chinese never-smokers with lung adenocarcinoma harbor known oncogenic driver mutations in just four genes: EGFR, ALK, HER2, and KRAS. Here, we examined the status of known driver mutations specifically in female never-smokers with lung adenocarcinoma.
Experimental Design
Tumors were genotyped for mutations in EGFR, KRAS, ALK, HER2, and BRAF. Data on age, stage, tumor differentiation, histological subtypes, and molecular alterations were recorded from 349 resected lung adenocarcinomas from female never-smokers. We further compared the clinicopathological parameters according to mutational status of these genes.
Results
Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations. In univariate analysis, patients harboring EGFR mutations were significantly older (p<0.001), whereas patients harboring HER2 mutations were significantly younger (p=0.036). Higher prevalence of KRAS (p=0.028) and HER2 (p=0.021) mutations was found in invasive mucinous adenocarcinoma (IMA). The frequency of EGFR mutations was positively correlated with acinar predominant tumors (p=0.002). Multivariate analysis revealed that older age at diagnosis (p=0.013) and acinar predominant subtype (p=0.005) were independent predictors of EGFR mutations. Independent predictors of HER2 mutations included younger age (p=0.030) and IMA (p=0.017). IMA (p=0.006) and poor differentiation (p=0.028) were independently associated with KRAS mutations.
Conclusions
The frequency of driver mutations in never-smoking female lung adenocarcinoma varies with histological subtypes and age at diagnosis. These data have implications for both clinical trial design and therapeutic strategies.
doi:10.1158/1078-0432.CCR-11-2511
PMCID: PMC3319848  PMID: 22317764
Lung adenocarcinoma; Female; Never smoker; EGFR mutation; HER2 mutation; Acinar; Mucinous; Age
3.  Spectrum of Oncogenic Driver Mutations in Lung Adenocarcinomas from East Asian Never Smokers 
PLoS ONE  2011;6(11):e28204.
Purpose
We previously showed that 90% (47 of 52; 95% CI, 0.79 to 0.96) of lung adenocarcinomas from East Asian never-smokers harbored well-known oncogenic mutations in just four genes: EGFR, HER2, ALK, and KRAS. Here, we sought to extend these findings to more samples and identify driver alterations in tumors negative for these mutations.
Experimental Design
We have collected and analyzed 202 resected lung adenocarcinomas from never smokers seen at Fudan University Shanghai Cancer Center. Since mutations were mutually exclusive in the first 52 examined, we determined the status of EGFR, KRAS, HER2, ALK, and BRAF in stepwise fashion as previously described. Samples negative for mutations in these 5 genes were subsequently examined for known ROS1 fusions by RT-PCR and direct sequencing.
Results
152 tumors (75.3%) harbored EGFR mutations, 12 (6%) had HER2 mutations, 10 (5%) had ALK fusions all involving EML4 as the 5′ partner, 4 (2%) had KRAS mutations, and 2 (1%) harbored ROS1 fusions. No BRAF mutation were detected.
Conclusion
The vast majority (176 of 202; 87.1%, 95% CI: 0.82 to 0.91) of lung adenocarcinomas from never smokers harbor mutant kinases sensitive to available TKIs. Interestingly, patients with EGFR mutant patients tend to be older than those without EGFR mutations (58.3 Vs 54.3, P = 0.016) and patient without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs 57.9, P = 0.013). Collectively, these data indicate that the majority of never smokers with lung adenocarcinoma could benefit from treatment with a specific tyrosine kinase inhibitor.
doi:10.1371/journal.pone.0028204
PMCID: PMC3227646  PMID: 22140546
4.  Lung Adenocarcinoma From East Asian Never-Smokers Is a Disease Largely Defined by Targetable Oncogenic Mutant Kinases 
Journal of Clinical Oncology  2010;28(30):4616-4620.
Purpose
To determine the proportion of lung adenocarcinomas from East Asian never-smokers who harbor known oncogenic driver mutations.
Patients and Methods
In this surgical series, 52 resected lung adenocarcinomas from never-smokers (< 100 cigarettes in a lifetime) at a single institution (Fudan University, Shanghai, China) were analyzed concurrently for mutations in EGFR, KRAS, NRAS, HRAS, HER2, BRAF, ALK, PIK3CA, TP53 and LKB1.
Results
Forty-one tumors harbored EGFR mutations, three harbored EML4-ALK fusions, two harbored HER2 insertions, and one harbored a KRAS mutation. All mutations were mutually exclusive. Thus, 90% (47 of 52; 95% CI, 0.7896 to 0.9625) of lung adenocarcinomas from never-smokers were found to harbor well-known oncogenic mutations in just four genes. No BRAF, NRAS, HRAS, or LKB1 mutations were detected, while 15 had TP53 mutations. Four tumors contained PIK3CA mutations, always together with EGFR mutations.
Conclusion
To our knowledge, this study represents the first comprehensive and concurrent analysis of major recurrent oncogenic mutations found in a large cohort of lung adenocarcinomas from East Asian never-smokers. Since drugs are now available that target mutant EGFR, HER2, and ALK, respectively, this result indicates that prospective mutation testing in these patients should successfully assign a targeted therapy in the majority of cases.
doi:10.1200/JCO.2010.29.6038
PMCID: PMC2974342  PMID: 20855837

Results 1-4 (4)