RESUMEN
Identifying the risk factors responsible for lung cancer especially for nonsmokers is critical for both its prevention and treatment. Studies have linked the polymorphisms in N-acetyltransferases (NAT2), a key enzyme for metabolism of hydrocarbons, with lung cancer in Asian female nonsmokers. Since a high percentage of lung adenocarcinoma in Asian female nonsmokers contains activating hotspot mutations in epidermal growth factor receptors (EGFR), we hypothesized that NAT2 polymorphisms might represent a risk factor in lung cancer with EGFR mutations. We studied NAT polymorphisms in 117 nonsmall cell lung cancer (NSCLC) patients and in 119 healthy controls and EGFR hotspot mutations in exons 18-21 in 100 of the 117 patients using polymerase chain reactions. NAT2 fast acetylator genotypes were significantly associated with patients with lung cancer (P = 0.04, odds ratio (OR): 1.90, 95% confidence interval (CI): 1.02-3.57). Further analyses revealed that NAT2 fast acetylator genotypes were significantly associated with NSCLC with wildtype EGFR (P = 0.008, OR: 3.16, 95% CI: 1.31-7.63), but not with those with EGFR mutations (P = 0.40). Therefore, NAT2 fast acetylator genotypes are a potential risk factor especially for lung cancer with wildtype EGFR.
Asunto(s)
Arilamina N-Acetiltransferasa/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético/genética , Acetilación , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Arilamina N-Acetiltransferasa/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Estudios de Casos y Controles , Receptores ErbB/metabolismo , Femenino , Genotipo , Humanos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Reacción en Cadena de la Polimerasa , Pronóstico , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: Resection is the treatment of choice for patients with stage I non-small cell lung cancer. Stage I non-small cell lung cancer has been further subdivided into IA (T1N0M0, tumor size < or = 3 cm without visceral pleural invasion) and IB (T2N0M0, tumor size > 3 cm or any size with visceral pleural invasion). The aim of this study was to evaluate the prognostic factors in patients with resected stage I non-small cell lung cancer with a diameter of 3 cm or less. METHODS: We retrospectively reviewed the clinicopathologic characteristics of 445 patients with resected stage I non-small cell lung cancer with a diameter of 3 cm or less who were treated at Taipei Veterans General Hospital between 1980 and 2000. Disease-free survival, overall survival, and their predictors were analyzed. RESULTS: The 5- and 10-year overall survivals were 61.4% and 40.0%, respectively. The 5- and 10-year disease-free survivals were 74.5% and 73.4%, respectively. Tumor size, smoking index, and number of mediastinal lymph nodes dissected were significant predictors for both disease-free survival (P = .009, P = .002, and P = .006, respectively) and overall survival (P = .004, P < .001, and P = .001, respectively) in multivariate analyses. Visceral pleural invasion did not influence overall survival or disease-free survival. CONCLUSIONS: Tumor size, smoking index, and number of mediastinal lymph nodes dissected were prognostic factors for both overall survival and disease-free survival in resected stage I non-small cell lung cancer with a diameter of 3 cm or less. Small tumors (<3 cm) of stage IB (T2N0M0) non-small cell lung cancer with visceral pleural invasion should be treated as T1 disease and not T2 disease.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pleurales/patología , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear. METHODS: Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13 candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status. RESULTS: The average copy numbers (+/-SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3: 4.19 (+/-0.69); CCNL1: 5.24 (+/-0.67); SMC4L1: 2.01 (+/-0.16); EVI1: 2.02 (+/-0.12); hTERC: 5.28 (+/-0.54); SKIL: 2.71 (+/-0.14); EIF5A2: 1.95 (+/-0.12); ECT2: 9.18 (+/-1.68); PIK3CA: 8.13 (+/-1.17); EIF4G1: 1.07 (+/-0.05); SST: 3.07 (+/-0.25); TP63: 2.51 (+/-0.22); TFRC: 2.42 (+/-0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC and SKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and SST, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis. CONCLUSION: This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes (SSR3, SMC4L1, ECT2, and SST) were identified. TP63 is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.