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MUC5AC upstream complex repetitive region length polymorphisms are associated with susceptibility and clinical stage of gastric cancer.

ABSTRACT: MUC5AC was deemed to be involved in gastric carcinogenesis since aberrant MUC5AC expression has been repeatedly detected in patients with gastric cancer (GC). In this study, length polymorphisms in a complicated repetitive region adjacent to MUC5AC promoter were assessed in 230 patients with GC and 328 cancer-free controls. Alleles of 1.4 and 1.8 kb were significantly more prevalent in GC group than in controls. In contrast, 2.3 and 2.8 kb alleles occurred at significantly lower frequencies in patients than in controls. Alleles were then classified into susceptible (S; 1.4 and 1.8 kb), protective (P; 2.3 and 2.8 kb) and null (N; all other alleles) categories with respect to their linkage with the susceptibility to GC. Individuals with genotype SS had a 2.7-fold increased risk of GC occurrence, but PN genotype was associated with a significantly reduced risk of this cancer. Moreover, homozygous or heterozygous individuals with one or two copies of 1.4 kb allele showed an earlier age of onset and more advanced metastasis stage compared with patients without this allele (Bonferroni corrected p?=?1.35×10(-4) and 6.60×10(-4) accordingly), whereas homozygous patients with two copies of 1.8 kb allele were linked to less advanced GC TNM stage. Our results suggest that certain genetic variations in MUC5AC upstream repetitive region are associated with the susceptibility and progression of GC.

SUBMITTER: Wang C

PROVIDER: S-EPMC4041751 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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MUC5AC upstream complex repetitive region length polymorphisms are associated with susceptibility and clinical stage of gastric cancer.

Wang Chenghua C Wang Jinshen J Liu Yiqing Y Guo Xueliang X Zhang Chunqing C

PloS one 20140602 6

MUC5AC was deemed to be involved in gastric carcinogenesis since aberrant MUC5AC expression has been repeatedly detected in patients with gastric cancer (GC). In this study, length polymorphisms in a complicated repetitive region adjacent to MUC5AC promoter were assessed in 230 patients with GC and 328 cancer-free controls. Alleles of 1.4 and 1.8 kb were significantly more prevalent in GC group than in controls. In contrast, 2.3 and 2.8 kb alleles occurred at significantly lower frequencies in p ...[more]

PMID: 24887023

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Project description:BackgroundPrimary glomerulonephritis (GN) is the leading cause of chronic kidney disease (CKD) and frequently progresses into end stage renal diseases (ESRDs). Shorter leukocyte telomere length (LTL) has been implicated in the CKD susceptibility and diminished kidney function, however, it is unclear whether the variants in telomerase genes contribute to risk to GN/CKD/ESRD. Here we address this issue by determining their association with the genetic variants of rs12696304 at the telomerase RNA component (TERC) and rs2736100 at the telomerase reverse transcriptase (TERT) loci.MethodsThe study includes 769 patients (243 primary GN-derived CKD and 526 ESRD cases) and sex-/age-matched healthy controls. Genomic DNA was extracted from peripheral blood of both controls and patients. Genotyping of rs12696304 and rs2736100 variants was carried out using PCR-based assays. Leukocyte telomere length (LTL) was determined using quantitative PCR (qPCR).ResultsA significantly higher frequency of TERC rs12696304 G allele was observed in patients and associated with increased disease risk (C vs G: OR = 1.334, 95% CI 1.112-1.586, P = 0.001; CC + GC vs GG: OR = 1.334, 95% CI 1.122-1.586, P = 0.001). Further analyses showed that such significant differences were only present between female controls and patients (C vs G: OR = 1.483, 95% CI 1.140-1.929, P = 0.003; CC + GC vs CC: OR = 1.692, 95% CI 1.202-2.383, P = 0.003), but not males. There were no differences in rs2736100 variants between controls and patients, but female ESRD patients carried significantly higher C allele frequencies than did female controls (A vs C: OR = 1.306, 95% CI 1.005-1.698, P = 0.046; AA vs CC: OR = 1.781, 95% CI 1.033-3.070, P = 0.037). There was no difference in LTL between controls and patients.ConclusionsOur results reveal that the TERC rs12696304 and TERT rs2736100 polymorphisms, but not LTL per se, contribute to GN/CDK/ESRD risk.

Dataset Information

MUC5AC upstream complex repetitive region length polymorphisms are associated with susceptibility and clinical stage of gastric cancer.

Publications

MUC5AC upstream complex repetitive region length polymorphisms are associated with susceptibility and clinical stage of gastric cancer.

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