Abstract
IntroductionThe contribution of CDH1 germline variants to gastric cancer burden among young adults is unknown in Brazil. We aimed to evaluate the frequency of CDH1 germline variants and the diet/lifestyle habits in early age onset gastric cancer (EOGC, ≤ 55 years old) patients.MethodologyFrom 2013 to 2015, a total of 88 unrelated and consecutive patients diagnosed with EOGC were enrolled. All CDH1 exons and intronic boundaries were sequenced, and large genomic rearrangements were screened by MLPA. CDH1 transcription analysis was performed for variants that could potentially induce an effect on splicing. The diet and lifestyle habits of EOGC patients were compared to Brazilian population diet and lifestyle, obtained from governmental databases.ResultsOf 88 patients, the mean age at EOGC diagnosis was 39 years and 55% fulfilled the criteria for hereditary diffuse gastric cancer. The majority of the tumors were diffuse (74%) and poorly differentiated (80%). In total, 4 novel missense variants of uncertain significance (VUS) were identified: c.313T>A, c.387G>T, c.1676G>A, and c.1806C>A. The MLPA results revealed no rearrangements and CDH1 transcription analysis for variants of interest were inconclusive. EOGC patients had a higher red (OR:2.6, 95%CI:1.4–4.9) and processed (OR:3.1, 95%CI:1.6–6.0) meat intake and higher fruit consumption (OR:0.4, 95%IC:0.3–0.7) compared to eating habits of the Brazilian population.ConclusionsNo unequivocal pathogenic germline CDH1 variants were identified in Brazilian EOGC patients. Dietary habits may be associated with the EOGC development.
Highlights
The contribution of CDH1 germline variants to gastric cancer burden among young adults is unknown in Brazil
Among the hereditary forms, the most important genetic mechanism is associated with germline mutations in the CDH1 gene (E-cadherin gene type 1, epithelial cadherin, and OMIM #192,090), which encodes the protein called E-cadherin that is a transmembrane calciumdependent cell-adhesion molecule involved in cell-junction formation and the maintenance of epithelial integrity [5]
Given the fact that inherited risk factors involved in the development of gastric cancer in Brazil are largely unexplored, we investigated the incidence and mutational spectrum of germline CDH1 variants as well as environmental and lifestyle risk factors in Brazilian early onset gastric cancer patients
Summary
The contribution of CDH1 germline variants to gastric cancer burden among young adults is unknown in Brazil. We aimed to evaluate the frequency of CDH1 germline variants and the diet/lifestyle habits in early age onset gastric cancer (EOGC, ≤ 55 years old) patients. Results Of 88 patients, the mean age at EOGC diagnosis was 39 years and 55% fulfilled the criteria for hereditary diffuse gastric cancer. Conclusions No unequivocal pathogenic germline CDH1 variants were identified in Brazilian EOGC patients. Frequency of CDH1 germline variants and contribution of dietary habits in early age onset gastric. CDH1 germline pathogenic mutations cause hereditary diffuse gastric cancer syndrome (HDGC) [6, 7]
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