Abstract
Background
Aberrant methylation patterns in CpG island are known to be influential in gene silencing. Histamine plays important physiological roles in the upper gastrointestinal tract and ...acts via the H2 receptor. We report an investigation into the effect of
HRH2
promoter polymorphism (rs2607474 G > A) on the methylation of
DAPK
and
CDH1
.
Methods
Non cancerous gastric mucosa samples were obtained from 115 subjects with gastric cancer (GC) and 412 non-cancer subjects (non-GC). Methylation status of genes was determined by MSP. The genotyping of rs2607474 was performed by PCR-SSCP.
Results
Methylation of
DAPK
and
CDH1
was observed in 296 and 246 subjects, respectively. The frequency of
CDH1
methylation in the subjects with GC was significantly lower in cancer lesion than in non cancerous mucosa, whereas that of
DAPK
methylation was not different. The allelic distribution of rs2607474 was 401GG, 119GA and 7AA. The GG homozygote was associated with a significantly increased risk for methylation of both
DAPK
and
CDH1
(p < 0.0001 and p = 0.0009, respectively). In the non-GC subjects or more than 60 years of age, GG homozygote was more closely associated with both
DAPK
and
CDH1
methylation. However, this genotype did not show an increased risk for the development of methylation of both genes in patients with GC. In
H. pylori
negative subjects, GG homozygote showed an increased risk for the methylation of both
DAPK
and
CDH1
(p = 0.0074 and p = 0.0016, respectively), whereas this genotype was associated with an increased risk for the development of
DAPK
methylation in
H. pylori
positive subjects (p = 0.0018). In addition, in subjects older than 60 years of age, atrophy and metaplasia scores were significantly higher in the GG homozygote (p = 0.011 and p = 0.039, respectively) and a significant correlation was observed between age and atrophy or metaplasia.
Conclusions
Our results suggest that rs2607474 GG homozygote confers a significantly increased risk for age- and inflammation-related
DAPK
and
CDH1
methylation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present study aimed to investigate whether single nucleotide polymorphisms in receptor interacting serine/threonine kinase 2 (
), which encodes a component of the nucleotide binding ...oligomerization domain containing 2-RIP2 pathway, may compromise the innate immune response to
infection, leading to increased susceptibility to gastric cancer in the Japanese population. The present case control study investigated the associations between
single nucleotide polymorphisms and gastric mucosal inflammation, atrophy and cancer susceptibility in 528 patients with gastric cancer and 697 patients without gastric malignancies on upper gastro-duodenal endoscopy. Overall, the
rs16900627 minor allele was significantly associated with the susceptibility to gastric cancer OR, 1.37; 95% confidence interval (CI), 1.06-1.77; P=0.016, particularly of the intestinal type (OR, 1.53; 95% CI, 1.13-2.07; P=0.0062). It was also significantly associated with gastric mucosal atrophy (OR, 1.83; 95% CI, 1.14-2.93; P=0.011). When assessing the severity of chronic gastritis using the updated Sydney system, the activity and inflammation scores, as well as atrophy and metaplasia scores, were significantly higher in rs16900627 minor allele carriers compared with wild-type homozygotes. In patients younger than 60 years old, the pepsinogen I/II ratio was significantly lower in rs16900627 minor allele carriers compared with wild-type homozygotes (P=0.037). The rs16900627 minor allele is associated with the severity of gastric mucosal inflammation and the development of gastric mucosal atrophy. Carriers of this allele may have an increased risk for the development of gastric cancer, particularly of the intestinal type.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We herein report the case of a 79-year-old patient with unresectable stage III non-small cell lung cancer who developed immune-related hepatitis caused by durvalumab administration. Durvalumab was ...administered at 10 mg/kg every two weeks after the treatment with carboplatin (AUC2), paclitaxel (35 mg/m2), and 60 Gy radiation. At the day 208 in which the 14th durvalumab administration was scheduled, the patient was urgently hospitalized due to CTCAE Grade 4 hepatic dysfunction detected during the an outpatient blood sampling test. He was diagnosed with immune-related hepatitis and started on methylprednisolone 60 mg/day. After 51 days, his liver dysfunction improved and he was discharged.
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