Dataset Information

Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection.

ABSTRACT: BACKGROUND:The single-nucleotide polymorphism SLC39A6 rs1050631 is strongly implicated in esophageal squamous cell carcinoma, leading us to question whether it may also play a role in gastric adenocarcima (GA). METHODS:We genotyped the SLC39A6 rs1050631 in 512 patients who underwent GA resection. All study subjects lived in an area of China with high GA incidence. Genotypes were examined for possible correlation with survival and recurrence. The potential involvement of SLC39A6 in gastric cancer was explored in clinical samples and cell culture studies. RESULTS:Multivariable analysis showed that patients with the CT?+?TT genotype at SLC39A6 rs1050631 were at greater risk of recurrence (hazard ratio, HR 1.387, p?=?0.004) and death (HR 1.429, p?=?0.002) than patients with CC genotype. Median recurrence-free and overall survival were significantly shorter in patients with the CT?+?TT genotype (20, 27?months) than in patients with the CC genotype (36, 43?months, p?=?0.001, p?

SUBMITTER: Gao J

PROVIDER: S-EPMC6839152 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection.

Gao Jian J Ren Wenjun W Xiao Chunhong C Wang Lie L Huang Qiaojia Q Zhang Zaizhong Z Dang Yuan Y Weng Pengcheng P Wang Hui H Fang Xuehong X Zhuang Minxian M Lin Liying L Chen Shaoquan S

BMC cancer 20191108 1

<h4>Background</h4>The single-nucleotide polymorphism SLC39A6 rs1050631 is strongly implicated in esophageal squamous cell carcinoma, leading us to question whether it may also play a role in gastric adenocarcima (GA).<h4>Methods</h4>We genotyped the SLC39A6 rs1050631 in 512 patients who underwent GA resection. All study subjects lived in an area of China with high GA incidence. Genotypes were examined for possible correlation with survival and recurrence. The potential involvement of SLC39A6 in ...[more]

PMID: 31703635

Similar Datasets

Project description:The majority of endocervical adenocarcinomas (EAs) are caused by human papillomavirus (HPV). Gastric-type EA, the second most common EA and unrelated to HPV, is biologically different with a more aggressive clinical course. Our knowledge of the molecular fingerprint of these important EA types and its role in diagnosis, prognosis and management is still evolving. Thus, we sought to evaluate the genomic profile of HPV-related and gastric EA. Clinical information including patient outcome was gathered for 56 tumors (45 HPV-associated and 11 gastric-type) surveying evaluated by a targeted massively parallel sequencing assay (OncoPanel platform) which surveys exonic DNA sequences of 447 cancer genes and 191 regions across 60 genes for rearrangement detection. KRAS, TP53, and PIK3CA were the most commonly mutated genes (10, 10, and 9 cases, respectively). Alterations in TP53, STK11, CDKN2A, ATM, and NTRK3 were significantly more common in gastric-type EA (P<0.05, Fisher exact test). Disease recurrence and/or death occurred in 14/49 (29%) cases with clinical information available 7 HPV-related (18% of HPV-related cases with clinical information available) and 7 gastric-type (64% of gastric-type cases with clinical information available). Tumors associated with adverse outcome, regardless of histotype, more commonly had alterations in KRAS (2 HPV-related, 4 gastric-type), GNAS (3 HPV-related, 1 gastric-type), and CDKN2A (0 HPV-related, 3 gastric type) compared with indolent-behaving cases (P<0.05, Fisher exact test). A total of 8/56 (14%) tumors harbored at least one actionable mutation; of these, 6 (75%) were associated with recurrence and/or cancer-related death. Copy number variations were detected in 45/56 cases (80%). The most frequent were chromosome 20 gain and 16q loss, identified in 7 cases each (all HPV-associated EA). The mutational profile of EA is diverse and correlates with clinical behavior and EA subtype. Thus, targeted sequencing assays can potentially serve as a diagnostic and prognostic tool. It can also identify targetable alterations, which may benefit patients with recurrent/metastatic disease.

Project description:BackgroundThe goal of surveillance testing is to enable curative salvage therapy through early disease detection, however supporting evidence in gastroesophageal adenocarcinoma is limited. We evaluated frequency of successful salvage therapy and outcomes in patients who underwent surveillance.MethodsA single-site, retrospective cohort study was conducted to identify all patients who received curative resection for gastroesophageal adenocarcinoma. Surveillance testing were those investigations not triggered by abnormal symptoms, physical examination, or blood tests. Successful salvage therapy was any potentially curative therapy for disease recurrence which resulted in postrecurrence disease-free survival ?2 years. Time-to-event data were analyzed using the Kaplan-Meier method and log rank tests.ResultsBetween 2011 and 2016, 210 consecutive patients were reviewed. Esophageal (14%), gastroesophageal junction (40%), and gastric adenocarcinomas (45%) were treated with surgery alone (29%) or multimodality therapy (71%). Adjuvant therapy was administered in 35%. At median follow-up of 38.3 months, 5-year overall survival (OS) rate was 56%. Among 97 recurrences, 53% were surveillance-detected, and 46% were symptomatic. None was detected by surveillance endoscopy. Median time-to-recurrence (TTR) was 14.8 months. Recurrences included locoregional only (4%), distant (86%), and both (10%). Salvage therapy was attempted in 15 patients, 4 were successful. Compared to symptomatic recurrences, patients with surveillance-detected recurrences had longer median OS (36.2 vs 23.7 months, P = .004) and postrecurrence survival (PRS, 16.5 vs 4.6 months, P < .001), but similar TTR (16.2 vs 13.3 months, P = .40) and duration of palliative chemotherapy (3.9 vs 3.3 months, P = .64).ConclusionsAmong patients surveyed, 96% of recurrences were distant, and salvage therapy was successful in only 1.9% of patients. Longer OS in patients with surveillance-detected compared to symptomatic recurrences was not associated with significant earlier disease detection, and may be contributed by differences in disease biology. Further prospective data are warranted to establish the benefit of surveillance testing in gastroesophageal adenocarcinoma.

Dataset Information

Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection.

Publications

Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets