Search

PDF - 2465K, Manhattan plot is used to evaluate the overall significance of the GWAS data using a trend p-value plot across the genome (A). Quantile-quantile plot is shown with the measured genetic inflation factor to reveal minimal overall inflation of the association results (B).

Purpose: Postoperative recurrence in stage I non–small cell lung cancer (NSCLC) is the major cause of a poor prognosis. This study aims to identify genetic variants that are associated with the prognosis of early-stage NSCLCs.Experimental Design: A genome-wide association study (GWAS) was conducted in 250 patients in stage I NSCLCs and the results were replicated in additional 308 patients.Results: Results from an Affymetrix Genome-wide Human SNP array in 250 patients identified 94 SNPs with significant associations (P < 2 × 10−4), which were selected for replication in 308 additional patients. Pooled analysis of the 558 patients determined that rs1454694 in chromosome 4q34 was the most significant marker of lung cancer prognosis in the stage I patients (adjusted HR = 2.81; P = 5.91 × 10−8). After the candidate loci were mapped, an additional four markers at chromosome 4q34.3 were significantly associated with recurrence-free survival (RFS; P < 5 × 10−5). A haplotype of five SNPs in 4q34 also showed significant association with RFS (P = 4.29 × 10−6).Conclusions: A genetic polymorphism rs1454694 was identified as a novel genetic risk factor for RFS of stage I NSCLCs. This genome-wide study suggests that genetic markers in 4q34.3 contribute to predict the prognosis of Korean patients with stage I NSCLCs. Clin Cancer Res; 20(12); 3272–9. ©2014 AACR.

Purpose: Postoperative recurrence in stage I non–small cell lung cancer (NSCLC) is the major cause of a poor prognosis. This study aims to identify genetic variants that are associated with the prognosis of early-stage NSCLCs. Experimental Design: A genome-wide association study (GWAS) was conducted in 250 patients in stage I NSCLCs and the results were replicated in additional 308 patients. Results: Results from an Affymetrix Genome-wide Human SNP array in 250 patients identified 94 SNPs with significant associations (P < 2 × 10−4), which were selected for replication in 308 additional patients. Pooled analysis of the 558 patients determined that rs1454694 in chromosome 4q34 was the most significant marker of lung cancer prognosis in the stage I patients (adjusted HR = 2.81; P = 5.91 × 10−8). After the candidate loci were mapped, an additional four markers at chromosome 4q34.3 were significantly associated with recurrence-free survival (RFS; P < 5 × 10−5). A haplotype of five SNPs in 4q34 also showed significant association with RFS (P = 4.29 × 10−6). Conclusions: A genetic polymorphism rs1454694 was identified as a novel genetic risk factor for RFS of stage I NSCLCs. This genome-wide study suggests that genetic markers in 4q34.3 contribute to predict the prognosis of Korean patients with stage I NSCLCs. Clin Cancer Res; 20(12); 3272–9. ©2014 AACR.

Supplemental Digital Content is available in the text, The role of pelvic radiotherapy (RT) in stage IV rectal cancer with total mesorectal excision (TME) has not been defined. We evaluated the impact of RT on oncologic outcomes among patients with stage IV rectal cancer who underwent TME and performed a meta-analysis of published studies. The records of stage IV rectal cancer patients who underwent TME between August 2001 and December 2011 were reviewed. Patients who received pelvic RT (RT group) and those who did not (non-RT group) were matched using a propensity score. Oncologic outcomes were compared between the groups. A systematic literature search and meta-analysis was conducted. One hundred seventy-six patients were matched with propensity score matching, resulting in 39 patients in each group. The local recurrence-free survival (LRFS) of the RT group was significantly higher than that of the non-RT group (2-year LRFS: 100% vs 83.6%, respectively, P = 0.038). The overall survival, disease-free survival, and systemic recurrence were not significantly different between the groups. In the meta-analysis, the RT group had a reduced risk for loco-regional recurrence than the non-RT group (RR: 0.48, 95% confidence interval: 0.29–0.79). Pelvic RT might have benefits for loco-regional control in patients with stage IV rectal cancer who undergo TME.

Circulating tumor DNA (ctDNA) has been known to be released from tumor cells and evaluated as potential biomarkers for therapeutic responses. In our previous study, we selected KRAS mutation and evaluated applicability as a prognostic marker through the quantitative analysis of plasma ctDNA. Then we proved that KRAS mutation of ctDNA from plasma is significant biomarker for prediction of clinical outcome in pancreatic ductal adenocarcinoma (PDA). Here we investigated whether KRAS mutation in urine ctDNA had the prognostic impact as shown of plasma ctDNA. Of the 106 patients enrolled, 67 were males and median age was 66 years. Total of 51 PDA has been enrolled in this study and the median age was 63 years old and 30 males (58.8%). Urine was separated by established centrifugation method and ctDNA were extracted using QIAamp Circulating Nucleic Acid Kit (Qiagen, Germany) from 4 mL of urine. Extracted ctDNA was quantified using the Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific, USA). QX200 Droplet Digital PCR System (Biorad, USA) was applied to measure frequency of KRAS mutation by KRAS screening multiplex droplet digital PCR kit, which covers seven common mutation sites (Biorad, USA). Mutant concentration and fractional abundance were analyzed by QuantaSoft software (Biorad, USA). There was no significant difference between resectable (N=21), locally advanced (N=11) and metastatic (N=19) groups. When compared high versus low KRAS mutation concentration and KRAS fractional abundance group in each stage, high KRAS mutation groups showed short overall survival (p = 0.0321) in metastatic group. However, the correlation between plasma and urine was low (r=0.193) in metastatic group. This study represented the possibility of KRAS mutation concentration and fractional concentration of urine ctDNA as prognostic factors in metastatic PDA. Urine cfDNA role has not been well investigated in PDA. Urine is easy to obtain and is not well known for its mechanism. Therefore, we have conducted a pilot study and we will explore KRAS mutation status in urine ctDNA in further studies. (This study was supported by National Cancer Center, Korea, Grant no. 1510203.) Citation Format: Min Jeong Kwon, Min Kyeong Kim, Sang Myung Woo, Kyong-Ah Yoon, Yun Hee Kim, Boram Park, Jung Nam Joo, Sang Jae Park, Sun-Young Kong. Feasibility test of KRAS mutation in urine circulating tumor DNA in metastatic pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 581.

Background The purpose of this study is to evaluate the effect of postoperative chemotherapy on recurrence and survival in patients after resection of metastatic brain tumors from non-small cell lung cancers. Methods Patients who went through resection of a single metastatic brain tumor from non-small cell lung cancer from July 2001 to December 2012 were reviewed. Those selected were 77 patients who survived more than 3 months after surgery were selected. Among them, 44 patients received various postoperative systemic chemotherapies, 33 patients received postoperative adjuvant whole brain radiotherapy (WBRT). Local/distant recurrence rate, local/distant recurrence free survival, disease free survival (DFS), and overall survival were compared between the two groups. Results Among the 77 patients, there were 19 (24.7%) local recurrences. Local recurrence occurred in 7 (21.2%) of 33 patients in the adjuvant radiotherapy (RT) group and in 12 (27.3%) of the 44 patients in the chemotherapy group (p=0.542). Among the 77 patients, there were 34 (44.1%) distant recurrences. Distant recurrence occurred in 7 (21.2%) of the 33 patients in the adjuvant RT group and in 27 (61.4%) of the 44 patients in the chemotherapy group (p