Dataset Information

Investigation of TCF7L2, LEP and LEPR polymorphisms with esophageal squamous cell carcinomas.

ABSTRACT: Single nucleotide polymorphisms (SNPs) in energy metabolism related gene may be key agents in the development of human malignancies. In this study, we aimed to examine the association of transcription factor 7-like 2, Leptin (LEP) and LEP receptor (LEPR) polymorphisms with esophageal squamous cell carcinoma (ESCC). A total of 507 ESCC cases and 1,496 controls were enrolled. We found that LEPR rs6588147 AA genotype was associated with ESCC risk (AA vs. GG/GA: adjusted OR=1.90, 95%CI=1.00-3.61, P=0.049). In the stratified analyses, LEPR rs6588147 G>A polymorphism increased the risk of ESCC (<63 years subgroup: AA vs. GG: adjusted OR=2.58, 95%CI=1.00-6.62, P=0.049 and AA vs. GA/GG: adjusted OR=2.71, 95%CI=1.06-6.91, P=0.038; male subgroup: AA vs. GG: adjusted OR=2.19, 95%CI=1.02-4.67, P=0.044 and AA vs. GA/GG: adjusted OR=2.26, 95%CI=1.06-4.80, P=0.035). However, LEP rs7799039 A>G decreased the risk of ESCC (?63 years subgroup: GG vs. AA: adjusted OR=0.47, 95%CI=0.23-0.95, P=0.035 and GG vs. AA/AG: adjusted OR=0.48, 95%CI=0.24-0.96, P=0.038; BMI?24 kg/m2 subgroup: AG vs. AA: adjusted OR=0.66, 95%CI=0.45-0.99, P=0.044). In addition, LEPR rs1137101 G>A polymorphism decreased ESCC risk in some subgroups (ever smoking subgroup: GA vs. GG: adjusted OR=0.66, 95%CI=0.44-1.00, P=0.049; ever drinking subgroup: GA vs. GG: adjusted OR=0.54, 95%CI=0.31-0.95, P=0.031 and GA/AA vs. GG: adjusted OR=0.54, 95%CI=0.31-0.93, P=0.027). Our findings suggest that LEPR rs6588147 G>A polymorphism is associated with the increased risk of ESCC; however, LEP rs7799039 A>G and LEPR rs1137101 G>A polymorphisms may be protective factors for ESCC.

SUBMITTER: Qiu H

PROVIDER: S-EPMC5752507 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Investigation of TCF7L2, LEP and LEPR polymorphisms with esophageal squamous cell carcinomas.

Qiu Hao H Lin Xunting X Tang Weifeng W Liu Chao C Chen Yu Y Ding Hao H Kang Mingqiang M Chen Shuchen S

Oncotarget 20171117 65

Single nucleotide polymorphisms (SNPs) in energy metabolism related gene may be key agents in the development of human malignancies. In this study, we aimed to examine the association of transcription factor 7-like 2, Leptin (LEP) and LEP receptor (LEPR) polymorphisms with esophageal squamous cell carcinoma (ESCC). A total of 507 ESCC cases and 1,496 controls were enrolled. We found that LEPR rs6588147 AA genotype was associated with ESCC risk (AA vs. GG ...[more]

PMID: 29312594

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Project description:BackgroundEsophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for >95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S.CasesThe patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations.MethodsNext-generation sequencing-based comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a median coverage depth of >650× for all coding exons of 315 cancer-related genes plus selected introns from 28 genes frequently rearranged in cancer. Results from a single sample were evaluated for all classes of genomic alterations (GAs) including point mutations, short insertions and deletions, gene amplifications, homozygous deletions, and fusions/rearrangements. Clinically relevant genomic alterations (CRGAs) were defined as alterations linked to approved drugs and those under evaluation in mechanism-driven clinical trials.ResultsThere were no significant differences by sex for either tumor type, and the median age for all patients was 63 years. All ESCCs and EACs were at an advanced stage at the time of sequencing. All 71 ESCCs and 231 EACs featured GAs on profiling, with 522 GAs in ESCC (7.4 per sample) and 1,303 GAs in EAC (5.6 per sample). The frequency of clinically relevant GAs in ESCC was 94% (2.6 per sample) and 93% in EAC (2.7 per sample). CRGAs occurring more frequently in EAC included KRAS (23% EAC vs. 6% ESCC) and ERBB2 (23% EAC vs. 3% ESCC). ESCC samples were enriched for CRGA in PIK3CA (24% ESCC vs. 10% EAC), PTEN (11% ESCC vs. 4% EAC), and NOTCH1 (17% ESCC vs. 3% EAC). Other GAs that differed significantly between histologic tumor types included SMAD4 (14% EAC vs. 1% ESCC), RB1 (14% ESCC vs. 2% EAC), SOX2 (18% ESCC vs. 1% EAC), and NFE2L2 (24% ESCC vs. 1% EAC).ConclusionESCC and EAC share similarly high frequencies of overall and clinically relevant genomic alterations; however, the profiles of genomic alterations in the two diseases differ widely, with KRAS and ERBB2 far more frequently altered in EAC compared with ESCC and with mammalian target of rapamycin (MTOR) pathway genes (PIK3CA and PTEN) and NOTCH1 more frequently altered in ESCC compared with EAC. Comprehensive genomic profiling highlights the promise of identifying clinically relevant genomic alterations in both ESCC and EAC and suggests new avenues for molecularly directed therapies in esophageal cancer.

Dataset Information

Investigation of TCF7L2, LEP and LEPR polymorphisms with esophageal squamous cell carcinomas.

Publications

Investigation of <i>TCF7L2, LEP</i> and <i>LEPR</i> polymorphisms with esophageal squamous cell carcinomas.

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