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1.
Sci Rep ; 13(1): 13271, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582820

RESUMO

The rs2736100 (A > C) polymorphism of the second intron of Telomerase reverse transcriptase (TERT) has been confirmed to be closely associated with the risk of Lung cancer (LC), but there is still no unified conclusion on the results of its association with LC. This study included Genome-wide association studies (GWAS) and case-control studies reported so far on this association between TERT rs2736100 polymorphism and LC to clarify such a correlation with LC and the differences in it between different ethnicities and different types of LC. Relevant literatures published before May 7, 2022 on 'TERT rs2736100 polymorphism and LC susceptibility' in PubMed, EMbase, CENTRAL, MEDLINE databases were searched through the Internet, and data were extracted. Statistical analysis of data was performed in Revman5.3 software, including drawing forest diagrams, drawing funnel diagrams and so on. Sensitivity and publication bias analysis were performed in Stata 12.0 software. The C allele of TERT rs2736100 was associated with the risk of LC (Overall population: [OR] = 1.21, 95%CI [1.17, 1.25]; Caucasians: [OR] = 1.11, 95%CI [1.06, 1.17]; Asians: [OR] = 1.26, 95%CI [1.21, 1.30]), and Asians had a higher risk of LC than Caucasians (C vs. A: Caucasians: [OR] = 1.11 /Asians: [OR]) = 1.26). The other gene models also showed similar results. The results of stratified analysis of LC patients showed that the C allele was associated with the risk of Non-small-cell lung carcinoma (NSCLC) and Lung adenocarcinoma (LUAD), and the risk of NSCLC and LUAD in Asians was higher than that in Caucasians. The C allele was associated with the risk of Lung squamous cell carcinoma (LUSC) and Small cell lung carcinoma(SCLC) in Asians but not in Caucasians. NSCLC patients ([OR] = 1.27) had a stronger correlation than SCLC patients ([OR] = 1.03), and LUAD patients ([OR] = 1.32) had a stronger correlation than LUSC patients ([OR] = 1.09).In addition, the C allele of TERT rs2736100 was associated with the risk of LC, NSCLC and LUAD in both smoking groups and non-smoking groups, and the risk of LC in non-smokers of different ethnic groups was higher than that in smokers. In the Asians, non-smoking women were more at risk of developing LUAD. The C allele of TERT rs2736100 is a risk factor for LC, NSCLC, and LUAD in different ethnic groups, and the Asian population is at a more common risk. The C allele is a risk factor for LUSC and SCLC in Asians but not in Caucasians. And smoking is not the most critical factor that causes variation in TERT rs2736100 to increase the risk of most LC (NSCLC, LUAD). Therefore, LC is a multi-etiological disease caused by a combination of genetic, environmental and lifestyle factors.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Telomerase , Humanos , Adenocarcinoma de Pulmão/etnologia , Adenocarcinoma de Pulmão/genética , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/genética , Estudos de Casos e Controles , Etnicidade , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Pulmão , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/genética , Telomerase/genética
2.
JAMA Netw Open ; 4(1): e2032276, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33433596

RESUMO

Importance: It has been established that disparities in race and socioeconomic status are associated with outcomes of non-small cell lung cancer. However, it remains unknown whether this extends to stage I, II, or III small cell lung cancer (SCLC), or limited-stage SCLC (L-SCLC). Objective: To investigate the associations of race, socioeconomic factors, and treatment characteristics with survival among patients with L-SCLC. Design, Setting, and Participants: Demographic information for patients with L-SCLC diagnosed between 2004 and 2014 was obtained from the National Cancer Database. The follow-up end point is death or last follow-up (date of last contact). Patients were divided into 5 mutually exclusive cohorts by race. Data analysis was performed in October 2019. Main Outcomes and Measures: Cox proportional hazards models were used to calculate univariable and multivariable models. Multivariable analyses were conducted to assess the associations of race and socioeconomic factors with risk-adjusted outcomes. Overall survival between groups was depicted by Kaplan-Meier curves. Results: Of 72 409 patients analyzed (median [range] age, 67.0 [23.0-90.0] years), 40 289 (55.6%) were women. The distribution of disease stage was 10 619 patients (14.7%) with stage I disease, 7689 patients (10.6%) with stage II disease, and 54 101 patients (74.7%) with stage III disease. The median (range) duration of follow-up was 8.2 (2.4-15.8) months. Compared with White patients, the hazard of death decreased to 0.92 (95% CI, 0.89-0.95; P < .001) for African American patients and 0.83 (95% CI, 0.77-0.91; P < .001) for Asian patients. The difference in median survival among different racial groups was significant only among those with stage III SCLC. Other factors associated with better survival were female sex, high income, high education, private insurance, diagnostic confirmation by positive cytological analysis, increase in number of sampled regional lymph nodes, and earlier stage at diagnosis. Conclusions and Relevance: This analysis highlights disparities in race and socioeconomic factors associated with outcomes of L-SCLC. Racial minorities, including African American and Asian patients, have better survival than White patients for L-SCLC after adjustment for sociodemographic factors.


Assuntos
Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/mortalidade , Fatores Raciais , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Classe Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Carcinoma de Pequenas Células do Pulmão/patologia , Análise de Sobrevida , Estados Unidos
3.
Cancer Discov ; 11(2): 240-244, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33318034

RESUMO

Small cell lung cancer (SCLC) is an aggressive disease with dismal survival rates and limited therapeutic options. SCLC development is strongly associated with exposure to tobacco carcinogens. However, additional genetic and environmental risk factors that contribute to SCLC pathogenesis are beginning to emerge. Here, we specifically assess disparities pertaining to SCLC in Black populations. In contrast to non-small cell lung cancer, preliminary data suggest that Black individuals may actually be at a lower risk of developing SCLC relative to white individuals. This difference remains unexplained but urgently needs to be verified in larger data sets, because it could provide important new insights and approaches to understanding this recalcitrant tumor. Importantly, little biological information exists on SCLC in Black individuals, and few patient-derived preclinical SCLC models from diverse ancestries are available in the laboratory. Unfortunately, we note strikingly low numbers of Black participants in clinical trials testing new treatments for SCLC. Evidence further indicates that care for patients with SCLC may vary between communities with a large fraction of Black patients and those without. Together, these observations underscore the need to better investigate genetic, environmental, and socioeconomic factors associated with SCLC development, preclinical research, clinical care, and outcomes.


Assuntos
Pesquisa Biomédica , Desigualdades de Saúde , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , População Negra , Avaliação Pré-Clínica de Medicamentos , Humanos , Neoplasias Pulmonares/etnologia , Oncologia , Carcinoma de Pequenas Células do Pulmão/etnologia
4.
Isr Med Assoc J ; 22(12): 788-793, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33381954

RESUMO

BACKGROUND: Lung cancer is the most common cause of cancer-related death. OBJECTIVES: To identify changing patterns of lung cancer and its histologic subtypes among different population groups in Israel over a 25 year period. METHODS: Primary lung cancers, all types and all stages, diagnosed during 1990-2014 were recorded in the Israel National Cancer Registry database. Demographic information was retrieved from the National Population Register. Age-standardized rates for the different subgroups were calculated for each year. Joinpoint software was used to analyze trends in incidence. RESULTS: We identified 42,672 lung cancer cases. The most common histology was adenocarcinoma (34%), followed by squamous cell carcinoma (19%), large cell/not-otherwise-specified (19%), other histologies (15%), and small cell lung cancer (11%). The adenocarcinoma incidence rose from 25.7% to 48.2% during the examined period. Large cell/not-otherwise-specified incidence peaked around 2005-2006 and declined after. Lung cancer incidence increased significantly for the population overall and specifically in Arab females, followed by Jewish females and by Arab males. Adenocarcinoma and small cell lung cancer increased in Jewish females and in Arab males. A younger age of diagnosis was seen in Arab compared to Jewish patients. CONCLUSIONS: Jewish females and Arab males and females living in Israel demonstrated a constant increase in lung cancer incidence, mostly in adenocarcinoma and small cell lung cancer incidence. In addition, a younger age of diagnosis in Arabs was noted. Smoking reduction interventions and screening should be implemented in those populations.


Assuntos
Árabes/estatística & dados numéricos , Judeus/estatística & dados numéricos , Neoplasias Pulmonares/epidemiologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/etnologia , Fatores Etários , Idoso , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Grandes/etnologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etnologia , Feminino , Humanos , Incidência , Israel/epidemiologia , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores Sexuais , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/etnologia
5.
Clin Lab ; 64(7): 1259-1268, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30146822

RESUMO

BACKGROUND: The diagnostic sensitivity and specificity of serum Pro-gastrin-releasing peptide (ProGRP) in benign or malignant diseases remains controversial. METHODS: The clinical data of 6,948 patients who were examined for ProGRP from February 2015 to January 2017 in the Zhongshan Hospital of the XiaMen University, were collected. The clinical data of the different groups were analyzed by statistical methods. RESULTS: The ProGRP reference levels were 68.50 pg/mL. The percentages of abnormal ProGRP levels were 23.87%, 26.14%, 22.87%, 84.56%, 16.1%, 15.59% and 43.75% for the pneumonia, cardiovascular disease, cerebral vascular disease, renal failure, small cell lung cancer (SCLC), colorectal cancer, and prostate cancer groups, respectively. The 95th percentile of the serum ProGRP concentration levels in the renal failure group was 364.22 pg/mL. The ProGRP cutoff levels for SCLC group were 162.90 pg/mL and the area under the receiver-operating characteristic curve (AUC) was 0.940 (95% CI, 0.892 to 0.987). The parameters sensitivity, specificity, PLR (positive likelihood ratio), NLR (negative likelihood) and Kappa value for the SCLC group with the exclusion of the renal failure group were 81.10% (95% CI: 38.19% - 89.71%), 99.51% (95% CI: 99.31% - 99.66%), 167.59 (95% CI: 116.06 - 241.99), 0.19 (95% CI: 0.11 - 0.32), and 0.6830 (Sig: 0.000), respectively. In the SCLC group, significantly higher concentrations of serum ProGRP of M1 were observed compared with M0. All esophageal neoplasms with high-level ProGRP were identified as small cell neoplasms. CONCLUSIONS: The ProGRP levels were increased in a variety of benign and malignant diseases and were considered a putative marker for SCLC with the exception of the renal failure group. It may be suggested that the high ProGRP levels originated from patients with neuroendocrine tumor.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/sangue , Peptídeos/sangue , Precursores de Proteínas/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , China , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/etnologia , Adulto Jovem
6.
N Z Med J ; 131(1479): 13-23, 2018 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-30048429

RESUMO

AIMS: This study aims to report the characteristics of newly diagnosed lung cancer cases, and to examine the data accuracy of registrations in the New Zealand Cancer Registry (NZCR) in 2011-2015. METHODS: The accuracy and completeness of lung cancer registrations in the NZCR was explored using the Midland Lung Cancer Register (MLCR, including Lakes, Waikato, Tairawhiti and Bay of Plenty District Health Boards) and clinical records. A combined Midland Lung Cancer Dataset was created based on the NZCR and the MLCR. The characteristics of lung cancer cases was described and compared between Maori and non-Maori patients. The subgroup differences were examined by Chi-Square tests. The odds ratio of having small cell lung cancer compared to non-small cell lung cancer between Maori patients and non-Maori patients was estimated using the logistic regression model. RESULTS: The combined Midland Lung Cancer Dataset included 2,057 verified lung cancer registrations, including 656 (31.9%) Maori patients and 1,401 (68.1%) non-Maori patients. Maori patients were more likely to be diagnosed at a younger age, more likely to be female, more likely to be a current or ex-smoker and more likely to have small cell lung cancer than non-Maori. The difference of cancer stage at diagnosis between Maori and others was not significant. After adjustment, the odds ratio of having small cell lung cancer for Maori patients compared to non-Maori patients was 1.55 (95% CI: 1.17-2.05). The adjusted odds ratio of having small cell lung cancer was 4.06 (95% CI: 1.72-9.60) for current smokers and 2.68 (95% CI: 1.14-6.30) for ex-smokers compared to patients who never smoked. CONCLUSIONS: Combining the two sources of data gives a more complete picture of the incidence and tumour characteristics of lung cancer in our region. Our dataset suggests that Maori patients are more likely to have small cell lung cancer than non-Maori patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Sistema de Registros/normas , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/etnologia , Confiabilidade dos Dados , Feminino , Humanos , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico/etnologia , Nova Zelândia/epidemiologia , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/etnologia , Fumar/etnologia , Fumar/mortalidade
7.
Sci Rep ; 6: 18999, 2016 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-26750506

RESUMO

Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six-, and nine-month progression-free survival were 63% (95% CI 57-69%, I(2) = 53%), 28% (95% CI 21-35%, I(2) = 71%), and 10% (95% CI 6-14%, I(2) = 41%), respectively. The pooled six-, 12-, and 18-month overall survival were 69% (95% CI 61-78%, I(2) = 83%), 36% (95% CI 28-44%, I(2) = 80%), and 15% (95% CI 8-21%, I(2) = 81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%.


Assuntos
Antraciclinas/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Topotecan/administração & dosagem , Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Povo Asiático , Humanos , Japão , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neutropenia/etiologia , Neutropenia/patologia , Recidiva , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Análise de Sobrevida , Topotecan/efeitos adversos , Resultado do Tratamento , População Branca
9.
Cancer Epidemiol Biomarkers Prev ; 23(11): 2250-65, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25368400

RESUMO

BACKGROUND: Lung cancer is one of the leading cancer sites diagnosed among Asian Americans, Pacific Islanders, and Native Hawaiians (AANHPI). To better understand the patterns of lung cancer incidence among AANHPIs, we examined the incidence trends of five histologic cell types of lung cancer across ten AANHPI populations in comparison with non-Hispanic Whites. METHODS: Lung cancer incidence data from 1990 through 2010 were obtained from 13 U.S. population-based cancer registries. Age-adjusted histologic cell-type-specific incidence rates and 95% confidence intervals were calculated. Joinpoint regression models and annual percentage change (APC) statistics were used to characterize the magnitude and direction of trends. RESULTS: From 1990 through 2010, incidence rates of adenocarcinoma increased significantly for Filipino and Korean women with a 2.6% and 3.0% annual percentage increase, respectively. More recently, a significant rise in the incidence of adenocarcinoma was observed for Chinese men (1996-2010; APC = 1.3%). Squamous cell carcinoma (SCC) increased 2.4% per year among Japanese women. For SCC, small cell lung carcinoma, large cell and other specified carcinoma, and unspecified types, stable or decreasing trends were observed in most AANHPI groups and non-Hispanic Whites. CONCLUSIONS: AANHPIs demonstrate a range in the burden of lung cancer across histologies and specific populations. IMPACT: These findings illustrate the importance of disaggregating AANHPIs into their specific populations. The rise in incidence of adenocarcinoma and SCC among certain AANHPIs demonstrates the need for research into non-tobacco associated risk factors for these populations and targeted efforts for tobacco prevention.


Assuntos
Adenocarcinoma/etnologia , Asiático/estatística & dados numéricos , Carcinoma de Células Grandes/etnologia , Carcinoma de Células Escamosas/etnologia , Neoplasias Pulmonares/etnologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Carcinoma de Pequenas Células do Pulmão/etnologia , Idoso , Idoso de 80 Anos ou mais , Ásia/etnologia , Feminino , Havaí/etnologia , Humanos , Incidência , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Programa de SEER , Fatores Sexuais , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos
10.
Mol Biol Rep ; 41(7): 4199-212, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24566690

RESUMO

Many studies have examined the association between the GSTP1 Ile105Val (rs 1695) gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case-control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 42 studies, comprising 12,304 lung cancer cases and 15,729 controls were included. Overall, for G allele carriers (GA + GG) versus homozygote AA, the pooled OR was 1.05 (95% CI 0.99-1.10 P = 0.092 for heterogeneity), for GG versus AA the pooled OR was 1.04 (95% CI 0.96-1.12 P = 0.084 for heterogeneity). In the stratified analysis by ethnicity, gender, histological types of lung cancer and smoking status, a significant association was found in Asians and smokers, not in Caucasian or mixed population, Male, Female population, lung AC, SCC, SCLC or non-smokers. Publication bias was found by using the funnel plot and Egger's test. Overall, there is no evidence showing a significant correlation between GSTP1 Ile105Val gene polymorphism and lung cancer risk in overall population, however stratified analysis by ethnicity, histology, gender and smoking status, it correlate with increased lung cancer susceptibility among Asians and smokers.


Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Glutationa S-Transferase pi/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Carcinoma de Pequenas Células do Pulmão/genética , Fumar/efeitos adversos , Adenocarcinoma/etnologia , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Alelos , Povo Asiático , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Masculino , Razão de Chances , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/etiologia , Carcinoma de Pequenas Células do Pulmão/patologia
11.
Tumour Biol ; 34(6): 3967-79, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23852860

RESUMO

No clear consensus has been reached on the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene C609T polymorphism and lung cancer risk. We performed a meta-analysis to summarize the possible association. We conducted a computer retrieval of PubMed and Embase databases prior to May 2013. References of retrieved articles were also screened. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. According to the inclusion criteria, 25 articles (32 studies) were finally included. There was no statistical association between C609T polymorphism and lung cancer risk in overall, East Asians, African Americans, or Hispanics. In Caucasians, a significant association was found in allele comparison model (T vs. C) (P = 0.04, OR = 1.09, 95% CI 1.00-1.19, P(heterogeneity) = 0.24, fixed-effects model). In the subgroup of squamous cell carcinoma, a borderline significance could be found in the dominant genetic model (TT + CT vs. CC) (P = 0.05, OR = 1.20, 95% CI 1.00-1.43, P(heterogeneity) = 0.65, fixed-effects model). Significant association could also be found in allele comparison (T vs. C) (P = 0.03, OR = 1.21, 95% CI 1.01-1.44, P(heterogeneity) = 0.68, fixed-effects model). In the subgroup of small cell lung cancer risk, significant association were found in allele comparison (T vs. C) (P = 0.03, OR = 1.68, 95%CI 1.05-2.68, P(heterogeneity) = 0.10, random-effects model) and in the homozygote comparison (TT vs. CC) (P = 0.02, OR = 2.79, 95% CI 1.14-6.85, P heterogeneity = 0.72, fixed-effects model). No association was observed in adenocarcinoma subgroup. Our study suggested that NQO1 C609T polymorphism might associate with lung cancer risk in Caucasians. This polymorphism might also associate with squamous cell carcinoma and small cell lung cancer risk.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , NAD(P)H Desidrogenase (Quinona)/genética , Polimorfismo de Nucleotídeo Único , Adenocarcinoma/etnologia , Adenocarcinoma/genética , Negro ou Afro-Americano/genética , Povo Asiático/genética , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Hispânico ou Latino/genética , Humanos , Neoplasias Pulmonares/etnologia , Viés de Publicação , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/genética , População Branca/genética
12.
J Thorac Oncol ; 8(4): 391-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23454887

RESUMO

INTRODUCTION: Black/white disparities in lung cancer incidence and mortality mandate an evaluation of underlying biological differences. We have previously shown higher risks of lung cancer associated with prior emphysema in African American compared with white patients with lung cancer. METHODS: We therefore evaluated a panel of 1440 inflammatory gene variants in a two-phase analysis (discovery and replication), added top genome-wide association studies (GWAS) lung cancer hits from white populations, and 28 single-nucleotide polymorphisms (SNPs) from a published gene panel. The discovery set (477 self-designated African Americans cases, 366 controls matched on age, ethnicity, and gender) were from Houston, Texas. The external replication set (330 cases and 342 controls) was from the EXHALE study at Wayne State University. RESULTS: In discovery, 154 inflammation SNPs were significant (p < 0.05) on univariate analysis, as was one of the gene panel SNPs (rs308738 in REV1, p = 0.0013), and three GWAS hits, rs16969968 p = 0.0014 and rs10519203 p = 0.0003 in the 15q locus and rs2736100, in the HTERT locus, p = 0.0002. One inflammation SNP, rs950286, was successfully replicated with a concordant odds ratio of 1.46 (1.14-1.87) in discovery, 1.37 (1.05-1.77) in replication, and a combined odds ratio of 1.40 (1.17-1.68). This SNP is intergenic between IRF4 and EXOC2 genes. We also constructed and validated epidemiologic and extended risk prediction models. The area under the curve (AUC) for the epidemiologic discovery model was 0.77 and 0.80 for the extended model. For the combined datasets, the AUC values were 0.75 and 0.76, respectively. CONCLUSIONS: As has been reported for other cancer sites and populations, incorporating top genetic hits into risk prediction models, provides little improvement in model performance and no clinical relevance.


Assuntos
Biomarcadores Tumorais/genética , Negro ou Afro-Americano/genética , Neoplasias Pulmonares/etiologia , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética , Adenocarcinoma/etnologia , Adenocarcinoma/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/etiologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/etiologia , Adulto Jovem
13.
Cancer Epidemiol Biomarkers Prev ; 22(2): 251-60, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23221128

RESUMO

BACKGROUND: Genome-wide association studies of European and East Asian populations have identified lung cancer susceptibility loci on chromosomes 5p15.33, 6p22.1-p21.31, and 15q25.1. We investigated whether these regions contain lung cancer susceptibly loci in African-Americans and refined previous association signals by using the reduced linkage disequilibrium observed in African-Americans. METHODS: 1,308 African-American cases and 1,241 African-American controls from 3 centers were genotyped for 760 single-nucleotide polymorphisms (SNP) spanning 3 regions, and additional SNP imputation was carried out. Associations between polymorphisms and lung cancer risk were estimated using logistic regression, stratified by tumor histology where appropriate. RESULTS: The strongest associations were observed on 15q25.1 in/near CHRNA5, including a missense substitution [rs16969968: OR, 1.57; 95% confidence interval (CI), 1.25-1.97; P, 1.1 × 10(-4)) and variants in the 5'-UTR. Associations on 6p22.1-p21.31 were histology specific and included a missense variant in BAT2 associated with squamous cell carcinoma (rs2736158: OR, 0.64; 95% CI, 0.48-0.85; P, 1.82 × 10(-3)). Associations on 5p15.33 were detected near TERT, the strongest of which was rs2735940 (OR, 0.82; 95% CI, 0.73-0.93; P, 1.1 × 10(-3)). This association was stronger among cases with adenocarcinoma (OR, 0.75; 95% CI, 0.65-0.86; P, 8.1 × 10(-5)). CONCLUSIONS: Polymorphisms in 5p15.33, 6p22.1-p21.31, and 15q25.1 are associated with lung cancer in African-Americans. Variants on 5p15.33 are stronger risk factors for adenocarcinoma and variants on 6p21.33 associated only with squamous cell carcinoma. IMPACT: Results implicate the BAT2, TERT, and CHRNA5 genes in the pathogenesis of specific lung cancer histologies.


Assuntos
Biomarcadores Tumorais/genética , Negro ou Afro-Americano/genética , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 5/genética , Cromossomos Humanos Par 6/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/etiologia , Polimorfismo de Nucleotídeo Único/genética , Adenocarcinoma/etnologia , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Idoso , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Mapeamento Cromossômico , Feminino , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Reação em Cadeia da Polimerase , Prognóstico , Proteínas/genética , Receptores Nicotínicos/genética , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/etiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Telomerase/genética
14.
Expert Rev Anticancer Ther ; 12(12): 1591-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23253224

RESUMO

Historically, notable variability has been observed in clinical trial outcomes between different regions and populations worldwide, even when employing the same cytotoxic regimen in lung cancer. These divergent results underscore the inherent challenges in interpreting trials conducted abroad and raise questions regarding the general applicability of transnational clinical trials. Various reasons have been postulated to account for these differences in efficacy and toxicity, including trial design, eligibility criteria, patient demographics and, perhaps most intriguingly, population-related pharmacogenomics. However, without methodology to control for such variables, these hypotheses remain largely untested. The authors previously developed the 'common arm' approach in order to directly compare efficacy and toxicity results of trials simultaneously performed in different countries. By standardizing clinical trial-associated variables such as treatment regimens (dose, schedule, and so on), eligibility, staging, response and toxicity criteria, this approach has the potential to determine the underlying reasons for divergences in trial outcomes across countries, and whether population-associated polymorphisms contribute to these differences. In the past decade, Japanese and US investigators have applied the common arm analytic method to trials in both extensive-stage small-cell lung cancer (SCLC) and advanced nonSCLC. In the SCLC analysis, a comparison of the cisplatin/irinotecan arms from both trials revealed significant differences in response rates and overall survival. Significant differences were also observed in the distribution of gender and performance status. The common arm analysis in nonSCLC included two trials from Japan and one from the USA, each containing a 'common' carboplatin/paclitaxel arm. Clinical results were similar in the two Japanese trials, but were significantly different from the US trial with regard to survival, neutropenia, febrile neutropenia and anemia. The underlying basis for these divergent outcomes is discussed. The common arm methodology provides a template for identifying and interpreting patient outcome differences across populations, and is an instructive lesson in the burgeoning era of clinical trials globalization.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos como Assunto , Internacionalidade , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Japão , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/genética , Farmacogenética , Projetos de Pesquisa , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/genética , Resultado do Tratamento , Estados Unidos
15.
Respirology ; 17(4): 699-706, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22404340

RESUMO

BACKGROUND AND OBJECTIVE: Genome-wide association studies (GWAS) have identified the three chromosomal regions, 5p15, 6p21 and 15q25, as being associated with lung cancer risk in European populations. This study was performed to confirm these associations in Korean patients with lung cancer. METHODS: The genotypes at rs2736100, rs402710, rs401681 and rs31489 at 5p15, rs9295740 at 6p22, which is in extensive linkage disequilibrium with the 6p21 region, as well as rs2036534 and rs6495309 at 15q25, were determined in 1094 patients with lung cancer and 1100 healthy control subjects, who were frequency matched for age and gender. RESULTS: The single-nucleotide polymorphisms (SNP) at 5p15 (rs2736100, adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.03-1.67, P = 0.025; rs402710, aOR 0.82, 95% CI 0.69-0.98, P = 0.025; rs401681, aOR 0.82, 95% CI 0.69-0.98, P = 0.026) and at 15q25 (rs2036534, aOR 0.75, 95% CI 0.61-0.93, P = 0.01; rs6495309, aOR 0.81, 95% CI 0.65-1.00, P = 0.052) were significantly associated with lung cancer risk. The magnitude of the effect was similar to that reported in previous studies, and the association was in the same direction. The effect of SNP in the 5p15 region on the risk of lung cancer was significant only for adenocarcinoma. The two SNP in the 15q25 region were significantly associated with lung cancer risk in ever-smokers and in patients with squamous-cell carcinoma. However, there was no association between the SNP at 6p22 and lung cancer risk. CONCLUSIONS: The association between SNP in the 5p15 and 15q25 regions and the risk of lung cancer was confirmed in a Korean population.


Assuntos
Adenocarcinoma/genética , Povo Asiático/genética , Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Carcinoma de Pequenas Células do Pulmão/genética , Adenocarcinoma/etnologia , Carcinoma de Células Escamosas/etnologia , Estudos de Casos e Controles , Humanos , Desequilíbrio de Ligação , Neoplasias Pulmonares/etnologia , Reprodutibilidade dos Testes , República da Coreia , Carcinoma de Pequenas Células do Pulmão/etnologia
16.
Clin Lung Cancer ; 13(2): 149-56, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22129972

RESUMO

RATIONALE: Airflow obstruction and/or emphysema have been associated with lung cancer risk; however, this relationship and the joint occurrence of these conditions are not well studied in the African American population OBJECTIVE: To describe the prevalence of airflow obstruction and/or emphysema in African Americans with lung cancer and to evaluate their impact on the management and outcome of lung cancer. METHODS: Medical records of 114 African Americans who had participated in population-based case-control studies of lung cancer and who sought medical care at the Karmanos Cancer Center in Detroit, Michigan, were reviewed. The medical records of these patients were reviewed for demographics, type and stage of lung cancer, spirometry, treatment, and outcome. Computed tomographies (CT) of the chest about the time of the diagnosis of lung cancer were reviewed by a radiologist for evidence of emphysema. COPD was diagnosed when there were changes consistent with emphysema on CTs and/or airflow obstruction by spirometry. RESULTS: There were no differences by sex for age at lung cancer diagnosis (P = .78) and tumor histology (P = .43). The men were more likely to present at a later stage of lung cancer diagnosis compared with the women (P = .04), and the women were more likely to have surgery than the men (P = .03). Overall, 94% of the men and 78% of the women in this population had spirometry and/or CT evidence of COPD. The men were somewhat more likely to have COPD diagnosed by either CT or spirometry than were the women (P = .06), but the Global Obstructive Lung Disease Classification scores did not differ by sex among those with spirometry-diagnosed COPD (P = .34). Seventy-eight percent of individuals who did not report a previous diagnosis of COPD had clinical evidence of COPD, whereas 94% of individuals who reported a previous diagnosis of COPD also had clinical evidence of COPD (P = .03). Among individuals who had both spirometry and CT data available, 29% had CT evidence of emphysema but normal spirometry. No differences in COPD diagnosis (P = .82) or emphysema diagnosis (P = .51) were noted by tumor histology. Stage at diagnosis also did not differ by COPD or emphysema diagnosis (P = .30 and P = .06, respectively), nor did treatment modality (P = .54 and P = .10, respectively). Patients with lung cancer and with COPD, diagnosed either via spirometry or CT, did not show an increased risk of death compared with patients with lung cancer and without COPD after adjusting for age at diagnosis, sex, and stage (hazard ratio, 1.31 [95% CI, 0.68-2.53]). CONCLUSION: There is a high incidence of COPD, emphysema in particular, in a selected group of African American patients with lung cancer. A significant number of these patients were not aware that they had COPD. There was no significant difference in the outcome of lung cancer in relation to the presence or absence of COPD.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/complicações , Doença Pulmonar Obstrutiva Crônica/etiologia , Enfisema Pulmonar/etiologia , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma Pulmonar de Células não Pequenas/etnologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/etnologia , Masculino , Prontuários Médicos , Michigan/epidemiologia , Pessoa de Meia-Idade , Prevalência , Prognóstico , Doença Pulmonar Obstrutiva Crônica/etnologia , Enfisema Pulmonar/etnologia , Fatores de Risco , Programa de SEER , Carcinoma de Pequenas Células do Pulmão/etnologia , Fumar/efeitos adversos
17.
Genet Test Mol Biomarkers ; 15(5): 301-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21254935

RESUMO

Recent studies have identified a negative correlation between serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and the risk of lung cancer. In this study, polymorphisms present at the -1590 site of the IGFBP-3 promoter were evaluated in relation to lung cancer risk in a Chinese Han population. A total of 248 nonsmall cell lung cancer (NSCLC) cases and 29 small cell lung cancer cases were compared with 252 matched, healthy controls. Polymerase chain reaction-based restriction fragment length polymorphism assays were used to detect polymorphisms present. The A/A genotype and an A allele were both associated with an increased risk of NSCLC after being adjusted for age and gender (adjusted odds ratio = 2.296, 95% confidence interval = 1.133-4.655; and adjusted odds ratio = 1.390, 95% confidence interval = 1.042-1.854, respectively). In conclusion, the A/A genotype and A allele of the IGFBP-3 promoter -1590 site may represent a genetic risk factor for NSCLC, with the A/A genotype being associated with a higher risk for squamous cell carcinoma than adenocarcinoma.


Assuntos
Povo Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Predisposição Genética para Doença/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , China/etnologia , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia
18.
Future Oncol ; 6(8): 1353-61, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20799879

RESUMO

This study compares the clinical presentation and characteristics of lung cancer among white and black patients according to place of birth, and correlates these factors to outcome. All newly diagnosed lung cancers from 2005 to 2007 in three tertiary medical centers were retrospectively reviewed; 767 patients were identified, 252 of whom were black. Age, sex, family history, place of birth, smoking history, insurance status, clinical stage, histology, grade of differentiation, symptoms, circumstance of diagnosis, treatment and outcome data were retrieved from medical charts. Lung cancer was diagnosed incidentally in 28.2% of white individuals versus 12.3% in black individuals (p < 0.0001). After adjustment for other variables, black and white individuals have similar survival rates (hazard ratio: 1.3; 95% CI: 0.8-2.0). The differences in lung cancer survival could be related to access to care, environmental factors and the biology of the disease. Including place of birth in cancer outcome studies could help understanding the origin of health disparity.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/patologia , Características de Residência/estatística & dados numéricos , População Branca/estatística & dados numéricos , Adenocarcinoma/etnologia , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Idoso , Carcinoma de Células Grandes/etnologia , Carcinoma de Células Grandes/secundário , Carcinoma de Células Grandes/terapia , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/etnologia , Carcinoma de Pequenas Células do Pulmão/secundário , Carcinoma de Pequenas Células do Pulmão/terapia , Taxa de Sobrevida
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