A multicenter study assessing the prevalence of germline genetic alterations in Chinese gastric cancer patients

Abstract Background: Approximately 10% of patients with gastric cancer (GC) have a genetic predisposition for the disease. To date, knowledge regarding germline mutations in predisposing genes in the Chinese GC population is scarce. The aim of this study was to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer. Methods: Forty patients from among ten families were recruited from seven medical institutions in China. Next-generation sequencing was performed on 171 genes associated with cancer predisposition. For probands with pathogenic/likely pathogenic germline variants, Sanger sequencing was used to validate the variants in the probands and their relatives. Results: Sequencing indicated that 25% (10/40) of the patients carried a combined total of ten pathogenic or likely pathogenic germline variants involving nine different genes: CDH1 (n = 1), MLH1 (n = 1), MSH2 (n = 1), CHEK2 (n = 1), BLM (n = 1), EXT2 (n = 1), PALB2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). Five of these variants have not previously been reported. In addition, a total of 129 variants of uncertain significance were identified in 27 patients. Conclusions: This study found that 25% of Chinese GC patients with hereditary high-risk factors have deleterious germline alterations. This result may indicate a unique genetic background of GC among Chinese patients.

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A multicenter study assessing the prevalence of germline genetic alterations in Chinese gastric cancer patients

10.21203/rs.2.18927/v1 ◽

2019 ◽

Author(s):

Yinjie Zhang ◽

Yang Yang ◽

Qing Wei ◽

Ting Xu ◽

Xiaotian Zhang ◽

...

Keyword(s):

Risk Factors ◽

Gastric Cancer ◽

High Risk ◽

Gene Mutations ◽

Genetic Alterations ◽

Chinese Patients ◽

Germline Variants ◽

High Risk Factors ◽

Uncertain Significance ◽

Gastric Cancer Patients

Abstract BackgroundApproximately 10% of patients with gastric cancer (GC) have a genetic predisposition for the disease. To date, knowledge regarding germline mutations in predisposing genes in the Chinese GC population is scarce. The aim of this study was to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer. Forty patients from among ten families were recruited from seven medical institutions in China. Next-generation sequencing was performed on 171 genes associated with cancer predisposition. For probands with pathogenic/likely pathogenic germline variants, Sanger sequencing was used to validate the variants in the probands and their relatives.ResultsSequencing indicated that 25% (10/40) of the patients carried a combined total of ten pathogenic or likely pathogenic germline variants involving nine different genes: CDH1 (n = 1), MLH1 (n = 1), MSH2 (n = 1), CHEK2 (n = 1), BLM (n = 1), EXT2 (n = 1), PALB2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). Five of these variants have not previously been reported. In addition, a total of 129 variants of uncertain significance were identified in 27 patients.ConclusionsThis study found that 25% of Chinese GC patients with hereditary high-risk factors have deleterious germline alterations. This result may indicate a unique genetic background of GC among Chinese patients.

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Significance of Immunohistochemical Findings of PCNA, Laminin, p53, nm23 and c-erbB-2 for High Risk Factors in Lymph Node Metastases in Early Gastric Cancer.

The Japanese Journal of Gastroenterological Surgery ◽

10.5833/jjgs.30.8 ◽

1997 ◽

Vol 30 (1) ◽

pp. 8-14

Author(s):

Takashi Shiroko ◽

Shigetoyo Saji ◽

Daizou Hukada ◽

Kiichi Miya ◽

Takao Umemoto ◽

...

Keyword(s):

Risk Factors ◽

Gastric Cancer ◽

Lymph Node ◽

High Risk ◽

Early Gastric Cancer ◽

Lymph Node Metastases ◽

High Risk Factors ◽

Node Metastases

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A multi-institutional investigation assessing prevalence of germline genetic alterations in Chinese patients with gastric carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13020 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13020-e13020

Author(s):

Yinjie Zhang ◽

Xicheng Wang ◽

Changbin Zhu ◽

Xiaotian Zhang ◽

Qing Wei ◽

...

Keyword(s):

Gastric Cancer ◽

Family History ◽

Gastric Carcinoma ◽

Familial Cancer ◽

Germline Mutations ◽

Genetic Alterations ◽

Chinese Patients ◽

Multiple Primary Cancers ◽

Cancer History ◽

Germline Variants

e13020 Background: Gastric carcinoma is one of the most common malignancies in east asian. Previous studies demonstrated around 10% of patients with gastric cancer were found to have pathogenic germline variants. While, predisposition genes of gastric cancer in Chinese patients are still largely unknown. Thus, we aim to delineate prevalence of deleterious germline mutations in Chinese gastric patients with hereditary high-risk familial cancer history. We also aim to analyze clinical relevance of deleterious germline mutations. Methods: Forty index cases were recruited from 7 institutions in China. DNA samples extracted from blood specimens were captured using a 171-cancer predisposition gene panel and then sequenced by MGI-SEQ 2000 platform. Germline variants were determined to be deleterious according to the ACMG 2015 guidelines. Pathogenic and Likely pathogenic germline variants were further validated by Sanger sequencing. Results: 12 of 40 (30%) probands had 13 pathogenic/likely pathogenic germline variants involving 11 different genes: CHEK2 (n = 2), SPINK1 (n = 2), BLM (n = 1), CDH1(n = 1), EXT2 (n = 1), MLH1 (n = 1), MSH2(n = 1), MUTYH (n = 1), PALB2 (n = 1), NF1 (n = 1), ERCC2 (n = 1). For patients with multiple primary cancers, pathogenic germline alterations were exclusively presented (5 out of 12) (P=0.003). Besides,27 germline variants (like EPCAM, RAD54B, FANCD2, FANCA) with uncertain significance in 15 patients were predicated to be deleterious via in silico predictors. Conclusions: This multi-institutional study identified 30% (12/40) of Chinese gastric cancer patients with family history to have deleterious germline alterations. And potential deleterious variants were also identified. Our data illustrates a significantly distinguished spectrum of germline variants compared with Caucasian ones. This may indicate unique carcinogenesis of gastric cancer in Chinese patients. Since patients with pathogenic or likely pathogenic germline variants have dismal clinical outcome and higher rate of multi-cancer occurrence, genetic counseling of gastric cancer should be considered for individuals with family history at their early age.

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Adjuvant oxaliplatin plus S-1 (SOX) with concurrent radiotherapy versus SOX alone for gastric cancer with D2 lymph node dissection and high risk factors: a randomized phase III trial

Annals of Oncology ◽

10.1093/annonc/mdx369.161 ◽

2017 ◽

Vol 28 ◽

pp. v267

Author(s):

X. Wang ◽

Y. Shen ◽

Q. Li ◽

M. Qiu ◽

Z. Li ◽

...

Keyword(s):

Risk Factors ◽

Gastric Cancer ◽

Lymph Node ◽

High Risk ◽

Phase Iii ◽

Node Dissection ◽

Phase Iii Trial ◽

D2 Lymph Node Dissection ◽

Concurrent Radiotherapy ◽

High Risk Factors

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Establish a Scoring Model for High-Risk Population of Gastric Cancer and Study on the Pattern of Opportunistic Screening

Gastroenterology Research and Practice ◽

10.1155/2020/5609623 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Wei Tao ◽

Hai-Xia Wang ◽

Yu-Feng Guo ◽

Li Yang ◽

Peng Li

Keyword(s):

Risk Factors ◽

Gastric Cancer ◽

Logistic Regression ◽

High Risk ◽

Sensitivity And Specificity ◽

Roc Curve ◽

Opportunistic Screening ◽

Scoring Model ◽

High Risk Factors ◽

Risk Scoring

Objective. To investigate and study the related risk factors of gastric cancer (GC) patients, to establish a high-risk scoring model of GC by multiple logistic regression analysis, and to explore the establishment of a GC screening mode with clinical opportunistic screening as the main method, and by using the pattern of opportunistic screening to establish the screening of high-risk GC patients and the choice of screening methods in the clinical outpatient work. Methods. Collected the epidemiological questionnaire of 99 GC cases and 284 non-GC patients (other chronic gastric diseases and normal) diagnosed by the General Hospital of Ningxia Medical University from October 2017 to March 2019. Serum pepsinogen (PG) levels were measured by enzyme-linked immunosorbent assay (ELISA) and confirmed Helicobacter pylori (Hp) infection in gastric mucosa tissues by Giemsa staining. Determined the high-risk factors and established a scoring model through unconditional logistic regression model analysis, and the ROC curve determined the cut-off value. Then, we followed up 26 patients of nongastric cancer patients constituted a validation group, which validated the model. Results. The high-risk factors of GC included age≥55, male, drinking cellar or well water, family history of GC, Hp infection, PGI≤43.6 μg/L, and PGI/PGII≤2.1. Established the high-risk model: Y=A×age+30×gender+30×drinking water+30×Hp infection+50×family history of GC+B×PG level. The ROC curve determined that the cut-off value for high-risk GC population was ≥155, and the area under the curve (AUC) was 0.875, the sensitivity and specificity were 87.9% and 71.5%. Conclusions. According to the risk factors of GC, using statistical methods can establish a high-risk scoring model of GC, and the score≥155 is divided into the screening cut-off value for high-risk GC population. Using this model for clinical outpatient GC screening is cost-effective and has high sensitivity and specificity.

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