Analysis of HDGC patients harbouring CDH1 alleles with PTCs at a wide variety of different positions indicates an association of their predicted ability to induce NMD and an earlier age of onset of gastric cancer.
Germline CDH1 mutations recently were identified in families with hereditary diffuse gastric carcinoma in a pattern suggestive of autosomal dominant inheritance with incomplete penetrance.
In meta-analysis, CDH1 -160C>A showed an inverse association with GC among Asians (OR, 0.76; 95% CI, 0.55-1.05) and a positive association among Caucasians (OR, 1.40; 95% CI, 0.95-2.04).
However, three CDH1 polymorphisms in the same haplotype block, including the CDH1-160C/A, interacted with smoking to increase GC risk in smokers but not in never smokers.
This study evaluated the effect of PTG on health-related quality of life (HRQL) in asymptomatic individuals with identified CDH1 mutations at high risk for gastric cancer.
In conclusion, this meta-analysis suggests that CDH1 -160 A-allele may play a protective role of stomach cancer development in Asians but not in Caucasians.
These results suggest that the ATCTG and CTTTG CDH1 haplotypes may be associated with an increased risk and decreased risk, respectively, of GC in the Japanese population.
To our knowledge, this is the first Korean case of presymptomatic detection of CDH1 mutation, and it highlights the importance of genetic screening for individuals with a family history of GC, especially in high-risk geographical areas.
CDH1 mutation testing in families with a history of gastric cancer and prophylactic gastrectomy in mutation-positive patients are recommended for the management of HDGC.
Participants included one 37-year-old man with multiple polyps in his stomach and a family history of stomach cancer, one 18 year-old man with a confirmed CDH1 mutation and a family history of stomach cancer, and one 33-year-old man with confirmed metastatic gastric adenocarcinoma.
We detected the epidermal growth factor receptor L858R, MSH2 R929* and telomerase reverse transcriptase amplification in the lung cancer specimen; CDH1 c.1320+1G>T mutation in the gastric cancer (GC) specimen; and MLH1 c.1896+5G>A germline mutation in the lung and GC specimens by 450 cancer-related gene mutations detection using next-generation sequencing technology.
In our area, in which a high rate of familial aggregation was demonstrated, the lack of germ line mutation of TP53 together with the infrequency of mutation of E-cadherin gene seem to limit the role of genetic predisposition in the development of gastric cancer.