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Introduction: The association between estrogen receptor (ER) gene polymorphism and lung cancer risk is rarely studied. This study aimed to explore the ER gene polymorphisms associated with the lung adenocarcinoma risk in never-smoking women. Methods: This study evaluated 532 never-smoking female patients with lung adenocarcinoma and 532 healthy controls. The ESR1 and ESR2 single nucleotide polymorphism (SNP) data were retrieved from a genome-wide association study. Using a multivariate-adjusted logistic regression assay, the associations of ESR1 and ESR2 SNPs with the lung adenocarcinoma risk were estimated. Expression quantitative trait loci analysis was performed to investigate the possible functional roles of ER gene SNPs. Results: For ESR1, seven tagged SNPs were identified. Among them, rs7753153 and rs985192 were associated with lung adenocarcinoma risk (rs7753153: odds ratios [OR], 1.509; 95% confidence intervals [CI], 1.168–1.950; rs985192: OR, 1.309; 95% CI, 1.001–1.712). For ESR2, only rs3020450 was associated with lung adenocarcinoma risk (OR, 2.110; 95% CI, 1.007–4.422). Subjects without hormone replacement therapy (HRT) use carrying at-risk genotypes had a significantly higher lung adenocarcinoma risk than subjects with HRT carrying no at-risk genotypes (rs7753153 GG: OR, 2.133; 95% CI, 1.415–3.216; rs985192 AA/AC, OR: 1.752, 95% CI: 1.109–2.768; rs3020450 AG/GG, OR: 7.162, 95% CI: 1.608–31.90). Risk genotypes of rs7753153 ( p = 0.0248) and rs9479122 ( p = 0.0251) were associated with decreased ESR1 expression. Conclusions: ER gene SNPs are associated with lung adenocarcinoma risk in never-smoking women. The joint effects of ER gene SNPs and HRT use on lung adenocarcinoma risk highlight the importance of the gene–environment interaction in lung carcinogenesis.

Introduction: Comorbidity may be an important prognostic factor in the treatment of small cell lung carcinoma (SCLC). This study aimed to investigate the prognostic values of simplified comorbidity score (SCS) in the treatment of patients with SCLC. Methods: The patients with SCLC admitted to the National Taiwan University Hospital during the period from January 2000 to December 2006 were included. The medical records were reviewed and analyzed. The SCS was used to evaluate comorbidities of the patients. A Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) for age, gender, and factors significantly associated with survival identified in univariate analyses. Results: A total of 172 patients were included; 56 patients had limited-stage disease and 116 had extensive-stage disease. Patients with an SCS more than 9 had shorter overall survival than those with SCS ≤9 both in limited-stage (372 days versus 581 days, p = 0.01) and extensive-stage disease (215 days versus 324 days, p = 0.001). Multivariate analysis indicated that SCS more than 9 was associated with a worse prognosis in patients with limited-stage disease (HR: 2.17, 95% CI: 1.12–4.21) and extensive-stage disease (HR: 1.74, 95% CI: 1.12–2.72), respectively. For patients with extensive-stage disease, SCS more than 9 was associated with poor treatment response (>9 versus ≤9, disease response rate: 60.0% versus 82.4%, p = 0.02). Conclusions: The SCS may be an independent prognostic factor for patients with SCLC. Large-scale prospective studies may be required to validate the prognostic value of the SCS for SCLC.

IntroductionLung cancer has become a disease of elderly. However, there are limited data describing the specific therapies, including epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), for octogenarians with advanced non-small cell lung cancer (NSCLC). This study is to characterize the treatment modalities and outcomes for octogenarians with advanced NSCLC and to investigate the impact of EGFR-TKI on survival.MethodsFrom January 2000 to December 2006, patients with NSCLC aged 80 years or older with stage IIIB or IV disease at National Taiwan University Hospital were included. The medical records were reviewed and analyzed. A Cox proportional hazard model was used to calculate the hazard ratio and its 95% confidence interval for gender, performance status, histologic types, disease stages, smoking history, comorbidities, and initial treatment modalities.ResultsA total of 203 patients were included. Sixty-five patients (32.0%) were treated with EGFR-TKI as the first-line therapy, and all of them were admitted after 2003. After 2003, the proportion of supportive care significantly decreased (p < 0.001), whereas those of chemotherapy and radiotherapy showed no significant change. There was a trend of an increase in median survival from 2003 (2000: 37 days, 2001: 62 days, 2002: 69 days, 2003: 110 days, 2004: 85 days, 2005: 188 days, and 2006: 195 days). When compared with those who received supportive care only, patients who received EGFR-TKI therapy had a significantly better prognosis (hazard ratio: 0.56, 95% confidence interval: 0.40–0.80), whereas no significant survival benefit was found in patients who received chemotherapy or radiotherapy.ConclusionFor octogenarians with advanced NSCLC, EGFR-TKI may play an important role in the initial treatment modalities. Further large-scale elderly specific clinical trials for EGFR-TKI as first-line therapy are warranted.

Introduction Germline Bcl-2-like protein 11 (BIM) deletion polymorphism in Asian is a poor predictive factor for treatment outcomes to tyrosine kinase inhibitors (TKIs) in malignancies. We explored the impact of BIM deletion polymorphism on treatment outcome of advanced non–small-cell lung cancer (NSCLC). Methods We prospectively collected tissue samples, blood, and clinical data from two cohorts of advanced NSCLC patients. BIM deletion polymorphism was correlated with overall survival (OS) and progression-free survival (PFS) to epidermal growth factor receptor (EGFR) TKIs and chemotherapy treatment. Results BIM deletion polymorphism was detected in blood of 16.2% (33 of 204) patients. The PFS to first-line EGFR-TKIs in 153 patients were 8.6 and 4.6 months for patients with wild-type BIM and BIM deletion polymorphism, respectively ( p = 0.004). Among 120 patients who received chemotherapies, the PFS to chemotherapies were 5.6 and 3.5 months for patients with wild-type BIM and BIM deletion polymorphism, respectively ( p = 0.050). The OS of all 204 patients was 24.8 and 16.8 months for patients with wild-type BIM and BIM deletion polymorphism, respectively ( p = 0.005). Multivariate analyses suggested that BIM deletion polymorphism was an independent predictor for shorter PFS to EGFR-TKIs (hazard ratio [HR] 2.15, p = 0.002), PFS to chemotherapy (HR 2.40, p = 0.016), and OS (HR 1.65, p = 0.039). Conclusions BIM deletion polymorphism predicts shorter PFS to EGFR-TKIs and OS in advanced NSCLC.