RESUMO
In this study, we examined the treatment and outcomes of pancreatic adenocarcinoma in New Mexico Native Americans (NA). METHODS: A retrospective review of patients treated for pancreatic adenocarcinoma at a university cancer center from 2002-2016 comparing demographic characteristics, disease presentation, treatment, and outcomes among three main ethnic groups in New Mexico. RESULTS: We identified 457 patients: 240 (52.5%) non-Hispanic Whites, 186 (40.7%) Hispanics, and 31 (6.8%) NA. Non-Hispanic Whites (OR 2.41; p=.026) and Hispanics (OR 2.37; p=.032) were more likely to receive or be offered chemotherapy than NA. More NA than non-Hispanic Whites died within one month of diagnosis (25.8% and 7.5%, respectively; p=.004). The NAs demonstrated a 26.2% one-year survival (CI 11.7-43.3), compared with 48.3% in non-Hispanic Whites (CI 40.9-55.2; p=.015). CONCLUSION: Significant disparities exist in the treatment and outcomes of pancreatic adenocarcinoma in New Mexico NA populations.
Assuntos
Adenocarcinoma/etnologia , Disparidades em Assistência à Saúde/etnologia , Indígenas Norte-Americanos/estatística & dados numéricos , Neoplasias Pancreáticas/etnologia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , New Mexico/epidemiologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos , Análise de Sobrevida , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations. RESULTS: Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0-1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746-750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7-19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2-36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4-35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05). CONCLUSIONS: Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/etnologia , Antineoplásicos/uso terapêutico , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Hispânico ou Latino/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/etnologia , Mutação , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Antineoplásicos/farmacologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Cloridrato de Erlotinib/farmacologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Gastric adenocarcinoma is associated with chronic infection by Helicobacter pylori and with the host inflammatory response triggered by it, with substantial inter-person variation in the immune response profile due to host genetic factors. AIM: To investigate the diversity of the proinflammatory genes IL8, its receptors and PTGS2 in Amerindians; to test whether candidate SNPs in these genes are associated with gastric cancer in an admixed population with high Amerindian ancestry from Lima, Peru; and to assess whether an IL8RB promoter-derived haplotype affects gene expression. METHODS: We performed a Sanger-resequencing population survey, a candidate-gene association study (220 cases, 288 controls) and meta-analyses. We also performed an in vitro validation by a reporter gene assay of IL8RB promoter. RESULTS: The diversity of the promoter of studied genes in Native Americans is similar to Europeans. Although an association between candidate SNPs and gastric cancer was not found in Peruvians, trend in our data is consistent with meta-analyses results that suggest PTGS2-rs689466-A is associated with H. pylori-associated gastric cancer in East Asia. IL8RB promoter-derived haplotype (rs3890158-A/rs4674258-T), common in Peruvians, was up-regulated by TNF-α unlike the ancestral haplotype (rs3890158-G/rs4674258-C). Bioinformatics analysis suggests that this effect stemmed from creation of a binding site for the FOXO3 transcription factor by rs3890158G>A. CONCLUSIONS: Our updated meta-analysis reinforces the role of PTGS2-rs689466-A in gastric cancer in Asians, although more studies that control for ancestry are necessary to clarify its role in Latin Americans. Finally, we suggest that IL8RB-rs3890158G>A is a cis-regulatory SNP.
Assuntos
Adenocarcinoma/etnologia , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Ciclo-Oxigenase 2/genética , Indígenas Sul-Americanos/genética , Interleucina-8/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/genética , Adenocarcinoma/metabolismo , Povo Asiático/genética , Sítios de Ligação , População Negra/genética , Estudos de Casos e Controles , Biologia Computacional , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Células HEK293 , Haplótipos , Humanos , Peru/epidemiologia , Fenótipo , Regiões Promotoras Genéticas , Fatores de Risco , Neoplasias Gástricas/metabolismo , Transfecção , População Branca/genéticaRESUMO
The aim of this study was to test for the possible association between vitamin D receptor (VDR) genetic variants and susceptibility to gallbladder cancer (GBC). A total of 291 GBC cases were recruited and 396 gender- and age-matched healthy volunteers were enrolled as controls. The VDR gene polymorphisms were determined in all subjects. The genotype and the allele frequencies of ApaI, BsmI, and TaqI polymorphisms were not significantly different between GBC subjects and controls. However, the genotype and allele frequencies of the FokI C>T polymorphism were significantly different between GBC subjects and controls. The FokI TT genotype was in markedly higher frequency in GBC subjects compared to controls (38.14 vs 22.73%, P < 0.001). Using TT as the reference genotype, multivariate logistic regression analysis showed that CC genotype carriers had a higher risk of GBC (adjusted odds ratio (OR) = 3.423, adjusted P = 0.001) with adjustment for age, gender, smoking status, alcohol use, and gallstone presence, as well as the serum 1,25(OH)2D level. Carriers of the CT genotype also had a higher risk of GBC (adjusted OR = 1.992, adjusted P = 0.003). Multivariate logistic regression analysis did not reveal any association between the ApaI, BsmI, and TaqI polymorphisms and GBC risk (all P > 0.05).
Assuntos
Adenocarcinoma/genética , Neoplasias da Vesícula Biliar/genética , Predisposição Genética para Doença , Polimorfismo Genético , Receptores de Calcitriol/genética , Adenocarcinoma/sangue , Adenocarcinoma/etnologia , Adenocarcinoma/patologia , Adulto , Consumo de Bebidas Alcoólicas/fisiopatologia , Alelos , Povo Asiático , Calcitriol/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Vesícula Biliar/metabolismo , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/etnologia , Neoplasias da Vesícula Biliar/patologia , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Receptores de Calcitriol/sangue , Fatores de Risco , Fumar/fisiopatologiaRESUMO
We made a meta-analysis of the association between X-ray cross-complementing gene 1 (XRCC1) genetic polymorphism Arg399Gln and esophageal cancer (EC) risk. Statistical analysis was performed with the Review Manager version 4.2.8 software program and STATA version 11.0. We selected 16 case-control studies for this meta-analysis, including 3591 EC cases and 5752 controls. Overall, the Gln399 allele was not associated with EC risk, compared with the Arg399 allele in the populations included in the analysis. However, stratified analysis revealed that the Gln399 allele was associated with increased EC risk among the Chinese population in a recessive model [odds ratio (OR) = 1.42; 95% confidence interval (95%CI) = 1.07-1.90; P = 0.02 for heterogeneity] and by homozygote contrast (OR = 1.43; 95%CI = 1.05-1.96; P = 0.02 for heterogeneity), particularly for the tumor histology of squamous cell carcinoma (OR = 1.46; 95%CI = 1.10-1.95 for the recessive model and OR = 1.42; 95%CI = 1.03-1.95 for the homozygote contrast). We conclude that the XRCC1 Arg399Gln polymorphism has potential as a biomarker for EC susceptibility in the Chinese population, particularly for squamous cell carcinoma.
Assuntos
Adenocarcinoma/genética , Povo Asiático/genética , Carcinoma de Células Escamosas/genética , Proteínas de Ligação a DNA/genética , Neoplasias Esofágicas/genética , Polimorfismo de Nucleotídeo Único , Adenocarcinoma/etnologia , Alelos , Carcinoma de Células Escamosas/etnologia , Estudos de Casos e Controles , China , Neoplasias Esofágicas/etnologia , Feminino , Genes Recessivos , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , População Branca/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
PURPOSES: Scientific literature has consistently shown the effects of certain diets on health but regional variations of dietary habits, and their relationship colorectal cancer (CRC) has been poorly studied in Argentina. Our aims were to identify dietary patterns and estimate their effect on CRC occurrence and to quantify the association between family history of CRC and CRC occurrence by applying multilevel models to estimate and interpret measures of variation. METHODS: Principal components factor analysis was performed to identify dietary patterns that were then used in a multilevel logistic regression applied to an ongoing case-control data about dietary exposure and CRC occurrence taking into account familiar clustering. RESULTS: Three dietary patterns were identified: "Southern Cone pattern" (red meat, wine, and starchy vegetables), "High-sugar drinks pattern", and "Prudent pattern". The study considered 41 cases and 95 controls. There was a significant promoting effects on CRC of "Southern Cone" (OR 1.5, 95%CI 1.0-2.2) and "High-sugar drinks" (OR 3.8, 95%CI 2.0-7.1) patterns, whereas "Prudent pattern" (OR 0.3, 95%CI 0.2-0.4) showed a significant protective effect at third tertile level. BMI, use of NSAIDs, and to have medical insurance showed significant effects. Variance of the random effect of family history of CRC was highly significant. CONCLUSIONS: This novel approach for Argentina showed that Southern Cone and High-sugar drinks patterns were associated with a higher risk of CRC, whereas the Prudent pattern showed a protective effect. There was a significant clustering effect of family history of CRC.
Assuntos
Adenocarcinoma/etiologia , Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Modelos Biológicos , Adenocarcinoma/epidemiologia , Adenocarcinoma/etnologia , Adenocarcinoma/prevenção & controle , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Argentina/epidemiologia , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/prevenção & controle , Dieta/etnologia , Saúde da Família , Comportamento Alimentar/etnologia , Feminino , Humanos , Incidência , Masculino , Carne/efeitos adversos , Pessoa de Meia-Idade , Análise de Componente Principal , Sistema de RegistrosRESUMO
BACKGROUND: Gastric cancer can progress from a chronic inflammation of the gastric mucosa resulting from Helicobacter pylori infection that activates the inflammatory response of the host. Therefore, polymorphisms in genes involved in the inflammatory response, such as inducible nitric oxide synthase (NOS2), have been implicated in gastric carcinogenesis. The aim of this study was to evaluate the association of NOS2 polymorphisms Ser608Leu (rs2297518) in exon 16, -954G/C and -1173C/T, both in the promoter region, with gastric cancer and chronic gastritis and the association of cancer with risk factors such as smoking, alcohol intake and H. pylori infection. METHODS: We conducted a population-based case-control study in 474 Southeast Brazilian individuals (150 with gastric cancer, 160 with chronic gastritis, and 164 healthy individuals), in which we performed NOS2 genotyping by PCR-RFLP. RESULTS: SNP Ser608Leu was not associated with risk of chronic gastritis or gastric cancer. The polymorphic allele -1173T was not found in the studied population. However, the frequency of -954GC+CC genotypes was significantly higher (p < 0.01) in the cancer group (48.7%) than in both the gastritis (28.1%) and the control (29.9%) groups. Multivariate logistic regression showed that the NOS2 SNP -954G/C was associated with higher risk of gastric cancer (OR = 1.87; 95% CI = 1.12-3.13). We also observed an association with risk factors such as smoking and alcohol intake in both the gastric cancer (OR = 2.68; 95% CI = 1.58-4.53; OR = 3.60; 95% CI = 2.05-6.32, respectively) and the chronic gastritis (OR = 1.93; 95% CI = 1.19-3.13; OR = 2.79; 95% CI = 1.55-5.02, respectively) groups. This is the first report of increased risk of gastric cancer in association with the -954G/C polymorphism. These findings show that several polymorphisms in the promoter region of the NOS2 gene may contribute to the susceptibility to gastric cancer. CONCLUSIONS: Polymorphism NOS2 -954 G/C, along with alcohol intake and tobacco smoking, is associated with gastric cancer. However, the NOS2 Ser608Leu polymorphism was not associated with gastric carcinogenesis. The NOS2 -1173C/T polymorphism was absent in the studied population.
Assuntos
Adenocarcinoma/etnologia , Adenocarcinoma/genética , Saúde Ambiental , Óxido Nítrico Sintase Tipo II/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Brasil , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Genótipo , Infecções por Helicobacter/complicações , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fumar/efeitos adversosRESUMO
BACKGROUND AND AIM: The incidence of esophageal adenocarcinoma has increased over the last 30 years, especially in non-Hispanic whites (nHw). Recent work indicates an increase in Hispanic Americans (HA). It is important to understand the effect of ethnicity on cancer occurrence over a prolonged interval. METHODS: We searched the New Mexico Tumor Registry for all cases of esophageal cancer from 1 January 1973 to 31 December 2002. Inclusion criteria were histologic diagnosis of adenocarcinoma or squamous cell carcinoma, ethnicity and gender. Incidence rates for both were compared among ethnic groups in 5-year intervals. RESULTS: Nine hundred eighty-eight patients met the criteria. Esophageal adenocarcinoma incidence rates/100,000 population increased significantly over 30 years; 1973-1977, 0.4 cases; 1978-1982, 0.4 cases; 1983-1987, 0.6 cases; 1988-1992, 1.2 cases, 1993-1997, 1.6 cases and 1998-2002, 2.2 cases; P < 0.001. Squamous cell carcinoma incidence rates remained unchanged during the interval. In nHw and HA, adenocarcinoma incidence rates increased significantly during the study period. In all minority groups, squamous cell carcinoma remained the major type. CONCLUSIONS: Esophageal adenocarcinoma incidence among nHw and HA increased from 1973 to 2002 in New Mexico. Squamous cell carcinoma remains predominant in minorities. Ethnicity may influence the histology or indicate an increased risk for certain types of esophageal cancer.
Assuntos
Adenocarcinoma/etnologia , Carcinoma de Células Escamosas/etnologia , Neoplasias Esofágicas/etnologia , Etnicidade/estatística & dados numéricos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Incidência , Indígenas Norte-Americanos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , New Mexico/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , População Branca/estatística & dados numéricosRESUMO
PURPOSE: To compare the perioperative outcomes in 2 initial series of open radical prostatectomy (ORP) and laparoscopic radical prostatectomy (LRP) in Asian men with prostate cancer. MATERIALS AND METHODS: From March 1999 to February 2007, the first 100 consecutive patients who underwent ORP and the first 100 consecutive patients who underwent LRP by the same surgeon (SL) were assessed. Mean age, clinical stage, preoperative PSA level, Gleason score, operative time, estimated blood loss, blood transfusion rate, perioperative complications, pathological stage and margin status were compared between the 2 groups. RESULTS: For each 100 patients in ORP and LRP, mean age and clinical stage were not significantly different. The operative time in LRP was significantly longer than ORP (188 +/- 55 versus 114 +/- 31 minute, p value = 0.01). Mean estimated blood loss and blood transfusion rate in LRP was significantly lower than ORP, 521 +/- 328 versus 809 +/- 510 mL (p value = 0.03) and 27% versus 55% (p value = 0.01), respectively. For pathological organ confined disease, the free surgical margin rate of ORP and LRP was not significantly different (88.9% versus 91.3%, respectively, p = 0.58). There was no significant major complication in either group. CONCLUSIONS: For initial experience by a single surgeon, LRP is comparable to ORP with no significant morbidity. LRP had longer operative time. However, LRP decreased blood loss and blood transfusion. For localized prostate cancer, free surgical margin rate of ORP and LRP was not significantly different.
Assuntos
Adenocarcinoma/cirurgia , Laparoscopia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Adenocarcinoma/etnologia , Adenocarcinoma/patologia , Idoso , Povo Asiático , Estudos de Viabilidade , Humanos , Masculino , Assistência Perioperatória , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , Resultado do TratamentoRESUMO
PURPOSE: To compare the perioperative outcomes in 2 initial series of open radical prostatectomy (ORP) and laparoscopic radical prostatectomy (LRP) in Asian men with prostate cancer. MATERIAL AND METHODS: From March 1999 to February 2007, the first 100 consecutive patients who underwent ORP and the first 100 consecutive patients who underwent LRP by the same surgeon (SL) were assessed. Mean age, clinical stage, preoperative PSA level, Gleason score, operative time, estimated blood loss, blood transfusion rate, perioperative complications, pathological stage and margin status were compared between the 2 groups. RESULTS: For each 100 patients in ORP and LRP, mean age and clinical stage were not significantly different. The operative time in LRP was significantly longer than ORP (188 ± 55 versus 114 ± 31 minute, p value = 0.01). Mean estimated blood loss and blood transfusion rate in LRP was significantly lower than ORP, 521 ± 328 versus 809 ± 510 mL (p value = 0.03) and 27 percent versus 55 percent (p value = 0.01), respectively. For pathological organ confined disease, the free surgical margin rate of ORP and LRP was not significantly different (88.9 percent versus 91.3 percent, respectively, p = 0.58). There was no significant major complication in either group. CONCLUSIONS: For initial experience by a single surgeon, LRP is comparable to ORP with no significant morbidity. LRP had longer operative time. However, LRP decreased blood loss and blood transfusion. For localized prostate cancer, free surgical margin rate of ORP and LRP was not significantly different.