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1.
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. 相似文献2.
Kuo-Hsuan Hsu Chao-Chi Ho Te-Chun Hsia Jeng-Sen Tseng Kang-Yi Su Ming-Fang Wu Kuo-Liang Chiu Tsung-Ying Yang Kun-Chieh Chen Hean Ooi Tzu-Chin Wu Hung-Jen Chen Hsuan-Yu Chen Chi-Sheng Chang Chung-Ping Hsu Jiun-Yi Hsia Cheng-Yen Chuang Chin-Hung Lin Jeremy J. W. Chen Kuan-Yu Chen Wei-Yu Liao Jin-Yuan Shih Sung-Liang Yu Chong-Jen Yu Pan-Chyr Yang Gee-Chen Chang 《PloS one》2015,10(3)
Background
It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations.Methods
This prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested. EGFR, KRAS, BRAF and HER2 mutations were assessed by MALDI-TOF MS (Cohort 1). EML4-ALK translocation was tested by Ventana method in EGFR-wild type patients (Cohort 2).Results
From August 2011 to November 2013, a total of 1772 patients with lung adenocarcinoma were enrolled. In Cohort 1 analysis, EGFR, KRAS, HER2 and BRAF mutations were identified in 987 (55.7%), 93 (5.2%), 36 (2.0%) and 12 (0.7%) patients, respectively. Most of these mutations were mutually exclusive, except for co-mutations in seven patients (3 with EGFR + KRAS, 3 with EGFR + HER2 and 1 with KRAS + BRAF). In Cohort 2 analysis, 29 of 295 EGFR-wild type patients (9.8%) were positive for EML4-ALK translocation. EGFR mutations were more common in female patients and non-smokers and KRAS mutations were more common in male patients and smokers. Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations. EML4-ALK translocation was more common in patients with younger age.Conclusion
This was the first study in Taiwan to explore the incidence of five oncogenic drivers in patients with lung adenocarcinoma and the results could be valuable for physicians in consideration of targeted therapy and inclusion of clinical trials. 相似文献3.
Jeet Gandhi Jianling Zhang Yang Xie Junichi Soh Hisayuki Shigematsu Wei Zhang Hiromasa Yamamoto Michael Peyton Luc Girard William W. Lockwood Wan L. Lam Marileila Varella-Garcia John D. Minna Adi F. Gazdar 《PloS one》2009,4(2)
Background
Deregulation of EGFR signaling is common in non-small cell lung cancers (NSCLC) and this finding led to the development of tyrosine kinase inhibitors (TKIs) that are highly effective in a subset of NSCLC. Mutations of EGFR (mEGFR) and copy number gains (CNGs) of EGFR (gEGFR) and HER2 (gHER2) have been reported to predict for TKI response. Mutations in KRAS (mKRAS) are associated with primary resistance to TKIs.Methodology/Principal Findings
We investigated the relationship between mutations, CNGs and response to TKIs in a large panel of NSCLC cell lines. Genes studied were EGFR, HER2, HER3 HER4, KRAS, BRAF and PIK3CA. Mutations were detected by sequencing, while CNGs were determined by quantitative PCR (qPCR), fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (aCGH). IC50 values for the TKIs gefitinib (Iressa) and erlotinib (Tarceva) were determined by MTS assay. For any of the seven genes tested, mutations (39/77, 50.6%), copy number gains (50/77, 64.9%) or either (65/77, 84.4%) were frequent in NSCLC lines. Mutations of EGFR (13%) and KRAS (24.7%) were frequent, while they were less frequent for the other genes. The three techniques for determining CNG were well correlated, and qPCR data were used for further analyses. CNGs were relatively frequent for EGFR and KRAS in adenocarcinomas. While mutations were largely mutually exclusive, CNGs were not. EGFR and KRAS mutant lines frequently demonstrated mutant allele specific imbalance i.e. the mutant form was usually in great excess compared to the wild type form. On a molar basis, sensitivity to gefitinib and erlotinib were highly correlated. Multivariate analyses led to the following results: 1. mEGFR and gEGFR and gHER2 were independent factors related to gefitinib sensitivity, in descending order of importance. 2. mKRAS was associated with increased in vitro resistance to gefitinib.Conclusions/Significance
Our in vitro studies confirm and extend clinical observations and demonstrate the relative importance of both EGFR mutations and CNGs and HER2 CNGs in the sensitivity to TKIs. 相似文献4.
Ling Shan Tian Qiu Yun Ling Lei Guo Bo Zheng Bingning Wang Wenbin Li Lin Li Jianming Ying 《PloS one》2015,10(6)
Aims
To determine the prevalence and clinicopathological characteristics of BRAF V600E mutation and HER2 exon 20 insertions in Chinese lung adenocarcinoma (ADC) patients.Methods
Given the fact that the driver mutations are mutually exclusive in lung ADCs, 204 EGFR/KRAS wild-type cases were enrolled in this study. Direct Sanger sequencing was performed to examine BRAF V600E and HER2 exon 20 mutations. The association of BRAF and HER2 mutations with clinicopathological characteristics was statistically analyzed.Results
Among the 204 lung ADCs tested, 11 cases (5.4%) carried HER2 exon 20 insertions and 4 cases (2.0%) had BRAF V600E mutation. HER2 mutation status was identified to be associated with a non-smoking history (p<0.05). HER2 mutation occurs in 9.4% of never smokers (10/106), 8.7% of female (8/92) and 2.7% of male (3/112) in this selected cohort. All four BRAF mutated patients were women and three of them were never-smokers. No HER2 mutant patients harbor BRAF mutation.Conclusions
HER2 and BRAF mutations identify a distinct subset of lung ADCs. Given the high prevalence of lung cancer and the availability of targeted therapy, Chinese lung ADC patients without EGFR and KRAS mutations are recommended for HER2 and BRAF mutations detection, especially for those never smokers. 相似文献5.
Paloma Cejas Miriam López-Gómez Cristina Aguayo Rosario Madero Javier de Castro Carpe?o Cristóbal Belda-Iniesta Jorge Barriuso Víctor Moreno García Javier Larrauri Rocío López Enrique Casado Manuel Gonzalez-Barón Jaime Feliu 《PloS one》2009,4(12)
Background
KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status.Methodology/Principal Findings
KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006).Conclusions/Significance
Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to metastasize to the lung. 相似文献6.
Laura S. Burke Paula L. Hyland Ruth M. Pfeiffer Jennifer Prescott William Wheeler Lisa Mirabello Sharon A. Savage Laurie Burdette Meredith Yeager Stephen Chanock Immaculata De Vivo Margaret A. Tucker Alisa M. Goldstein Xiaohong R. Yang 《PloS one》2013,8(8)
Introduction
Recent evidence suggests a link between constitutional telomere length (TL) and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations.Materials and Methods
We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT.Results
We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02–7.72, P = 0.04). The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002). One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002) after Bonferroni correction.Discussion
Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk. 相似文献7.
Hua Bai Zhijie Wang Yuyan Wang Minglei Zhuo Qinghua Zhou Jianchun Duan Lu Yang Meina Wu Tongtong An Jun Zhao Jie Wang 《PloS one》2013,8(2)
Purpose
This study evaluated occurrence and potential clinical significance of intratumoral EGFR mutational heterogeneity in Chinese patients with non-small cell lung cancer (NSCLC).Materials and Methods
Eighty-five stage IIIa-IV NSCLC patients who had undergone palliative surgical resection were included in this study. Of these, 45 patients carried EGFR mutations (group-M) and 40 patients were wild-type (group-W). Each tumor sample was microdissected to yield 28–34 tumor foci and Intratumoral EGFR mutation were determined using Denaturing High Performance Liquid Chromatography (DHPLC) and Amplification Refractory Mutation System (ARMS). EGFR copy numbers were measured using fluorescence in situ hybridization (FISH).Results
Microdissection yielded 1,431 tumor foci from EGFR mutant patients (group-M) and 1,238 foci from wild-type patients (group-W). The EGFR mutant frequencies in group-M were 80.6% (1,154/1,431) and 87.1% (1,247/1,431) using DHPLC and ARMS, respectively. A combination of EGFR-mutated and wild-type cells was detected in 32.9% (28/85) of samples by DHPLC and 28.2% (24/85) by ARMS, supporting the occurrence of intratumoral heterogeneity. Thirty-one patients (36.5%) were identified as EGFR FISH-positive. Patients harboring intratumoral mutational heterogeneity possessed lower EGFR copy numbers than those tumors contained mutant cells alone (16.7% vs. 71.0%, P<0.05). Among 26 patients who had received EGFR-TKIs, the mean EGFR mutation content was higher in patients showing partial response (86.1%) or stable disease (48.7%) compared with patients experiencing progressive disease (6.0%) (P = 0.001). There also showed relationship between progression-free survival (PFS) and different content of EGFR mutation groups (pure wild type EGFR, EGFR mutation with heterogeneity and pure mutated EGFR) (P = 0.001).Conclusion
Approximately 30% of patients presented intratumoral EGFR mutational heterogeneity, accompanying with relatively low EGFR copy number. EGFR mutant content was correlated with the response and prognosis of EGFR-TKIs. 相似文献8.
Junichi Soh Naoki Okumura William W. Lockwood Hiromasa Yamamoto Hisayuki Shigematsu Wei Zhang Raj Chari David S. Shames Ximing Tang Calum MacAulay Marileila Varella-Garcia T?nu Vooder Ignacio I. Wistuba Stephen Lam Rolf Brekken Shinichi Toyooka John D. Minna Wan L. Lam Adi F. Gazdar 《PloS one》2009,4(10)
9.
Yunyun Jiang Vivek Subbiah Filip Janku Joseph A. Ludwig Aung Naing Robert S. Benjamin Robert E. Brown Pete Anderson Razelle Kurzrock 《PloS one》2014,9(8)
Background
Ewing''s sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT.Methodology
Twenty eight patients with ES or DSRCT had tumor tissue available that could be analyzed by one of the following methods: 1) Next-generation exome sequencing platform; 2) Multiplex PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene mutation screening; 4) Sanger sequencing; 5) Morphoproteomics.Principal Findings
Novel somatic mutations were identified in four out of 18 patients with advanced ES and two of 10 patients with advanced DSRCT (six out of 28 (21.4%));KRAS (n = 1), PTPRD (n = 1), GRB10 (n = 2), MET (n = 2) and PIK3CA (n = 1). One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation achieved a complete remission (CR) on an Insulin like growth factor 1 receptor (IGF1R) inhibitor based treatment. One patient, who achieved a partial remission (PR) with IGF1R inhibitor treatment, but later developed resistance, demonstrated a KRAS mutation in the post-treatment resistant tumor, but not in the pre-treatment tumor suggesting that the RAF/RAS/MEK pathway was activated with progression.Conclusions
We have reported several different mutations in advanced ES and DSRCT that have direct implications for molecularly-directed targeted therapy. Our technology agnostic approach provides an initial mutational roadmap used in the path towards individualized combination therapy. 相似文献10.
11.
Shih-Hsin Hsiao H. Eugene Liu Hsin-Lun Lee Chii-Lan Lin Wei-Yu Chen Zhung-Han Wu Sey-En Lin Ling-Ling Chiang Chi-Li Chung 《PloS one》2013,8(12)
Introduction
Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been associated with favorable progression free survival (PFS) in patients with non-small cell lung cancers (NSCLC) harboring EGFR mutations. However, a subset of this population doesn''t respond to EGFR-TKI treatment. Therefore, the present study aimed to elucidate survival outcome in NSCLC EGFR-mutant patients who were treated with EGFR TKIs.Methods
Among the 580 consecutive NSCLC patients who were treated at our facility between 2008 and 2012, a total of 124 treatment-naïve, advanced NSCLC, EGFR-mutant patients treated with EGFR TKIs were identified and grouped into non-responders and responders for analyses.Results
Of 124 patients, 104 (84%) responded to treatment, and 20 (16%) did not; and the overall median PFS was 9.0 months. Notably, the PFS, overall survival (OS) and survival rates were significantly unfavorable in non-responders (1.8 vs. 10.3 months, hazard ratio (HR) = 29.2, 95% confidence interval (CI), 13.48–63.26, P<0.0001; 9.4 vs. 17.3 months, HR = 2.74, 95% CI, 1.52–4.94, P = 0.0008; and 58% vs. 82% in 6, 37% vs. 60% in 12, and 19 vs. 40% at 24 months, respectively). In multivariate analysis, treatment efficacy strongly affected PFS and OS, independent of covariates (HR = 47.22, 95% CI, 17.88–124.73, P<0.001 and HR = 2.74, 95% CI, 1.43–5.24, P = 0.002, respectively). However, none of the covariates except of the presence of EGFR exon 19 deletion in the tumors was significantly associated with better treatment efficacy.Conclusions
A subset of NSCLC EGFR-mutant patients displayed unfavorable survival despite EGFR TKI administration. This observation reinforces the urgent need for biomarkers effectively predicting the non-responders and for drug development overcoming primary resistance to EGFR TKIs. In addition, optimal therapeutic strategies to prolong the survival of non-responders need to be investigated. 相似文献12.
Antonio Marchetti Maela Del Grammastro Lara Felicioni Sara Malatesta Giampaolo Filice Irene Centi Tommaso De Pas Armando Santoro Antonio Chella Alba Ariela Brandes Paola Venturino Franco Cuccurullo Lucio Crinò Fiamma Buttitta 《PloS one》2014,9(8)
Introduction
Assessment of EGFR mutation in non-small cell lung cancer (NSCLC) patients is mandatory for optimization of pharmacologic treatment. In this respect, mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient''s disease status.Experimental Design
Blood samples were collected from 37 patients enrolled in the TRIGGER study, a prospective phase II multi-center trial of erlotinib treatment in advanced NSCLC patients with activating EGFR mutations in tumor tissue. 10 CTC preparations from breast cancer patients without EGFR mutations in their primary tumors and 12 blood samples from healthy subjects were analyzed as negative controls. CTC preparations, obtained by the Veridex CellSearch System, were subjected to ultra-deep next generation sequencing (NGS) on the Roche 454 GS junior platform.Results
CTCs fulfilling all Veridex criteria were present in 41% of the patients examined, ranging in number between 1 and 29. In addition to validated CTCs, potential neoplastic elements were seen in 33 cases. These included cells not fulfilling all Veridex criteria (also known as “suspicious objects”) found in 5 (13%) of 37 cases, and isolated or clustered large naked nuclei with irregular shape observed in 33 (89%) cases. EGFR mutations were identified by NGS in CTC preparations of 31 (84%) patients, corresponding to those present in matching tumor tissue. Twenty-five (96%) of 26 deletions at exon 19 and 6 (55%) of 11 mutations at exon 21 were detectable (P = 0.005). In 4 (13%) cases, multiple EGFR mutations, suggesting CTC heterogeneity, were documented. No mutations were found in control samples.Conclusions
We report for the first time that the CellSearch System coupled with NGS is a very sensitive and specific diagnostic tool for EGFR mutation analysis in CTC preparations with potential clinical impact. 相似文献13.
Jeng-Sen Tseng Chih-Liang Wang Ming-Shyan Huang Chung-Yu Chen Cheng-Yu Chang Tsung-Ying Yang Chi-Ren Tsai Kun-Chieh Chen Kuo-Hsuan Hsu Meen-Hsin Tsai Sung-Liang Yu Kang-Yi Su Chih-Wei Wu Cheng-Ta Yang Yuh-Min Chen Gee-Chen Chang 《PloS one》2014,9(9)
Introduction
Methods used for epidermal growth factor receptor (EGFR) mutation testing vary widely. The impact of detection methods on the rates of response to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-wild type (wt) lung adenocarcinoma patients is unknown.Methods
We recruited the Group-I patients to evaluate the efficacy of erlotinib in patients with EGFR-wt lung adenocarcinoma by either direct sequencing (DS) or mutant type-specific sensitive (MtS) methods in six medical centers in Taiwan. Cross recheck of EGFR mutations was performed in patients who achieved objective response to erlotinib and had adequate specimens. The independent Group-II lung adenocarcinoma patients whose EGFR mutation status determined by DS were recruited to evaluate the potential limitations of three MtS methods.Results
In Group-I analysis, 38 of 261 EGFR-wt patients (14.6%) achieved partial response to erlotinib treatment. Nineteen patients (50.0%) had adequate specimens for cross recheck of EGFR mutations and 10 of them (52.6%) had changes in EGFR mutation status, 5 in 10 by DS and 5 in 9 by MtS methods originally. In Group-II analysis, 598 of 996 lung adenocarcinoma patients (60.0%) had detectable EGFR mutations. The accuracy rates of the three MtS methods, MALDI-TOF MS, Scorpions ARMS and Cobas, were 87.8%, 86.8% and 85.8%, respectively.Conclusions
A significant portion of the erlotinib responses in EGFR-wt lung adenocarcinoma patients were related to the limitations of detection methods, not only DS but also MtS methods with similar percentages. Prospective studies are needed to define the proper strategy for EGFR mutation testing. 相似文献14.
Yoon-La Choi Jong-Mu Sun Juhee Cho Sanjay Rampal Joungho Han Bhash Parasuraman Eliseo Guallar Genehee Lee Jeeyun Lee Young Mog Shim 《PloS one》2013,8(2)
Introduction
Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea.Methods
Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records.Results
This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P<0.001). The median time elapsed between cancer diagnoses and receiving EGFR testing results was 21 days. EGFR testing was most frequently ordered by oncologists (57.7%), pulmonologists (31.9%), and thoracic surgeons (6.6%). EGFR testing was more commonly requested for women, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma.Conclusions
In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants the need for generalized testing in Asian NSCLC patients. 相似文献15.
Xiaoxia Xue Zhihua Yin Yao Lu Haibo Zhang Ying Yan Yuxia Zhao Xuelian Li Zeshi Cui Miao Yu Lu Yao Baosen Zhou 《PloS one》2013,8(8)
Background
The human 8-oxoguanine DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and adenosine diphosphate ribosyl transferase (ADPRT) genes play an important role in the DNA base excision repair pathway. Single nucleotide polymorphisms (SNPs) in critical genes are suspected to be associated with the risk of lung cancer. This study aimed to identify the association between the polymorphisms of hOGG1 Ser326Cys, APE1 Asp148Glu, and ADPRT Val762Ala, and the risk of lung adenocarcinoma in the non-smoking female population, and investigated the interaction between genetic polymorphisms and environmental exposure in lung adenocarcinoma.Methods
We performed a hospital-based case-control study, including 410 lung adenocarcinoma patients and 410 cancer-free hospital control subjects who were matched for age. Each case and control was interviewed to collect information by well-trained interviewers. A total of 10 ml of venous blood was collected for genotype testing. Three polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism technique.Results
We found that individuals who were homozygous for the variant hOGG1 326Cys/Cys showed a significantly increased risk of lung adenocarcinoma (OR = 1.54; 95% CI: 1.01–2.36; P = 0.045). When the combined effect of variant alleles was analyzed, we found an increased OR of 1.89 (95% CI: 1.24–2.88, P = 0.003) for lung adenocarcinoma individuals with more than one homozygous variant allele. In stratified analyses, we found that the OR for the gene-environment interaction between Ser/Cys and Cys/Cys genotypes of hOGG1 codon 326 and cooking oil fumes for the risk of lung adenocarcinoma was 1.37 (95% CI: 0.77–2.44; P = 0.279) and 2.79 (95% CI: 1.50–5.18; P = 0.001), respectively.Conclusions
The hOGG1 Ser326Cys polymorphism might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, there is a significant gene-environment association between cooking oil fumes and hOGG1 326 Cys/Cys genotype in lung adenocarcinoma among female non-smokers. 相似文献16.
17.
Objective
To explore the relationship between TTF-1 and EGFR mutations in lung adenocarcinoma tissues to guide clinical treatment timely and effectively.Materials and Methods
we collected 664 tissue samples from patients with histologically confirmed lung adenocarcinoma from May 2010 to April 2013. All tumor tissues were collected prior to administering therapy. TTF-1 was detected byimmunohistochemistry and EGFR mutations by DNA direct sequencing. Finally, the correlation between TTF-1 expression and the presence of EGFR mutations was analyzed using χ2 test or Fisher’s exact test with SPSS software version 18.0.Results
Of the 664 lung adenocarcinoma tissue samples, 18 were partially positive for TTF-1 (+−), and 636 were positive for TTF-1 (+) resulting in a total positive rate of 98.49% (+,+−)(including partial positive). In only 10 cases was the TTF-1 negative (−); the negative rate was 1.51%. There were 402 cases without an EGFR mutation and 262 cases with EGFR mutations; the rate of mutations was 39.46%. The location of the EGFR mutation was exon 19 for 121 cases resulting in a mutation rate in exon 19 of 18.22%. The location of the EGFR mutation was exon 21 for 141 cases resulting in a mutation rate in exon 21 of 21.23%. Exon 18 and 20 detected by DNA direct sequencing no mutations.A Fisher’s exact test was used to determine the correlation between EGFR mutations and TTF-1 expression.for the whole, TTF-1 positive expression(including partial positive) has correlation with EGFR mutations (p<0.001),especially for Exon 21 expression,the correlation is significant (p = 0.008).Conclusion
In lung adenocarcinomas, positive and partial positive TTF-1 expression has a significant positive correlation with EGFR mutations(exon 19 and 21). In clinical practice, TTF-1 expression combine with EGFR mutations, especially exon 21 mutation can guide clinical treatment timely for lung adenocarcinomas. 相似文献18.
19.
20.
Zacharenia Saridaki Maria Tzardi Chara Papadaki Maria Sfakianaki Fraga Pega Aristea Kalikaki Eleftheria Tsakalaki Maria Trypaki Ippokratis Messaritakis Efstathios Stathopoulos Dimitris Mavroudis Vassilis Georgoulias John Souglakos 《PloS one》2011,6(1)