Evidence map›Paper›PMID 32701958›Full record

ArticlePloS one2020

Family-based exome sequencing combined with linkage analyses identifies rare susceptibility variants of MUC4 for gastric cancer.

Yoon Jin Choi, Jung Hun Ohn, Nayoung Kim, Wonji Kim, Kyungtaek Park, Sungho Won, Lee Sael, Cheol Min Shin, Sun Min Lee, Sejoon Lee and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 2 countries.

Yoon Jin ChoiDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Jung Hun OhnDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Nayoung KimDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.ORCID 0000-0002-9397-0406
Wonji KimChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
Kyungtaek ParkInterdisciplinary Program of Bioinformatics, Seoul National University, Seoul, South Korea.
Sungho WonInterdisciplinary Program of Bioinformatics, Seoul National University, Seoul, South Korea.
Lee SaelDepartment of Artificial Intelligence and Data Science, Ajou University, Seoul, South Korea.
Cheol Min ShinDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Sun Min LeeDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Sejoon LeeDepartment of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea.
Hyun Joo AnGraduate School of Analytical Science and Technology, Chungnam National University, Daejeon, South Korea.
Dong Man JangTumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, South Korea.
Byung Woo HanTumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, South Korea.
Hye Seung LeeDepartment of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea.
Seung Joo KangDepartment of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, South Korea.ORCID 0000-0002-7401-8356
Joo Sung KimDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Dong Ho LeeDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Seoul National University · KRSeoul National University Bundang Hospital · KRAjou University · KRBrigham and Women's Hospital · USChungnam National University · KRSeoul National University Hospital · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genome-wide association studies of gastric cancer (GC) cases have revealed common gastric cancer susceptibility loci with low effect size. We investigated rare variants with high effect size via whole-exome sequencing (WES) of subjects with familial clustering of gastric cancer. WES of DNAs from the blood of 19 gastric cancer patients and 36 unaffected family members from 14 families with two or more gastric cancer patients were tested. Linkage analysis combined with association tests were performed using Pedigree Variant Annotation, Analysis, and Search Tool (pVAAST) software. Based on the logarithm of odds (LOD) and permutation-based composite likelihood ratio test (CLRT) from pVAAST, MUC4 was identified as a predisposing gene (LOD P-value = 1.9×10-5; permutation-based P-value of CLRT ≤ 9.9×10-9). In a larger cohort consisting of 597 GC patients and 9,759 healthy controls genotyped with SNP array, we discovered common variants in MUC4 regions (rs148735556, rs11717039, and rs547775645) significantly associated with GC supporting the association of MUC4 with gastric cancer. And the MUC4 variants were found in higher frequency in The Cancer Genome Atlas Study (TCGA) germline samples of patients with multiple cancer types. Immunohistochemistry indicated that MUC4 was downregulated in the noncancerous gastric mucosa of subjects with MUC4 germline missense variants, suggesting that loss of the protective function of MUC4 predisposes an individual to gastric cancer. Rare variants in MUC4 can be novel gastric cancer susceptibility loci in Koreans possessing the familial clustering of gastric cancer.

Indexed as

Exome SequencingGenetic LinkageGenetic Predisposition to DiseaseGenetic VariationCohort StudiesFamilyFemaleGerm CellsHumansMaleMiddle AgedMucin-4PedigreeReproducibility of ResultsStomachStomach NeoplasmsMUC4 protein, humanMucin-4

Identifiers

PMID32701958
PMCPMC7377420
OpenAlexW3045332485

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.