Rare variants confer shared susceptibility to gastrointestinal tract cancer risk Article Swipe
Ji Zheng
,
Xin Wang
,
Jingrao Li
,
Yuanna Wu
,
Jiang Chang
,
Junyi Xin
,
Meilin Wang
,
Tianpei Wang
,
Qingyi Wei
,
Mengyun Wang
,
Ruoxin Zhang
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fonc.2023.1161639
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fonc.2023.1161639
Background Cancers arising within the gastrointestinal tract are complex disorders involving genetic events that cause the conversion of normal tissue to premalignant lesions and malignancy. Shared genetic features are reported in epithelial-based gastrointestinal cancers which indicate common susceptibility among this group of malignancies. In addition, the contribution of rare variants may constitute parts of genetic susceptibility. Methods A cross-cancer analysis of 38,171 shared rare genetic variants from genome-wide association assays was conducted, which included data from 3,194 cases and 1,455 controls across three cancer sites (esophageal, gastric and colorectal). The SNP-level association was performed by multivariate logistic regression analyses for single cancer, followed by association analysis for SubSETs (ASSET) to adjust the bias of overlapping controls. Gene-level analyses were conducted by SKAT-O, with multiple comparison adjustments by false discovery rate (FDR). Based on the significant genes indicated by SKATO analysis, pathways analysis was conducted using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Results Meta-analysis in three gastrointestinal (GI) cancers identified 13 novel susceptibility loci that reached genome-wide significance ( P ASSET < 5×10 -8 ). SKAT-O analysis revealed EXOC6, LRP5L and MIR1263/LINC01324 to be significant genes shared by GI cancers ( P adj <0.05, P FDR <0.05). Furthermore, GO pathway analysis identified significant enrichment of synaptic transmission and neuron development pathways shared by all three cancer types. Conclusion Rare variants and the corresponding genes potentially contribute to shared susceptibility in different GI cancer types. The discovery of these novel variants and genes offers new insights for the carcinogenic mechanisms and missing heritability of GI cancers.
Related Topics
Concepts
Gastrointestinal tract
Cancer
Medicine
Gastrointestinal cancer
Bioinformatics
Biology
Cancer research
Internal medicine
Colorectal cancer
Metadata
- Type
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- Language
- en
- Landing Page
- https://doi.org/10.3389/fonc.2023.1161639
- OA Status
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- Cited By
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- OpenAlex ID
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All OpenAlex metadata
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https://openalex.org/W4383341707Canonical identifier for this work in OpenAlex
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https://doi.org/10.3389/fonc.2023.1161639Digital Object Identifier
- Title
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Rare variants confer shared susceptibility to gastrointestinal tract cancer riskWork title
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articleOpenAlex work type
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enPrimary language
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2023Year of publication
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2023-07-06Full publication date if available
- Authors
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Ji Zheng, Xin Wang, Jingrao Li, Yuanna Wu, Jiang Chang, Junyi Xin, Meilin Wang, Tianpei Wang, Qingyi Wei, Mengyun Wang, Ruoxin ZhangList of authors in order
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https://doi.org/10.3389/fonc.2023.1161639Publisher landing page
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goldOpen access status per OpenAlex
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https://doi.org/10.3389/fonc.2023.1161639Direct OA link when available
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Gastrointestinal tract, Cancer, Medicine, Gastrointestinal cancer, Bioinformatics, Biology, Cancer research, Internal medicine, Colorectal cancerTop concepts (fields/topics) attached by OpenAlex
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| abstract_inverted_index.performed | 93 |
| abstract_inverted_index.Background | 0 |
| abstract_inverted_index.Conclusion | 224 |
| abstract_inverted_index.Gene-level | 116 |
| abstract_inverted_index.comparison | 124 |
| abstract_inverted_index.conducted, | 71 |
| abstract_inverted_index.constitute | 51 |
| abstract_inverted_index.contribute | 232 |
| abstract_inverted_index.conversion | 16 |
| abstract_inverted_index.databases. | 158 |
| abstract_inverted_index.enrichment | 210 |
| abstract_inverted_index.identified | 166, 208 |
| abstract_inverted_index.mechanisms | 255 |
| abstract_inverted_index.regression | 97 |
| abstract_inverted_index.adjustments | 125 |
| abstract_inverted_index.association | 68, 91, 104 |
| abstract_inverted_index.development | 216 |
| abstract_inverted_index.genome-wide | 67, 173 |
| abstract_inverted_index.malignancy. | 24 |
| abstract_inverted_index.overlapping | 114 |
| abstract_inverted_index.potentially | 231 |
| abstract_inverted_index.significant | 134, 191, 209 |
| abstract_inverted_index.(esophageal, | 85 |
| abstract_inverted_index.Encyclopedia | 150 |
| abstract_inverted_index.Furthermore, | 204 |
| abstract_inverted_index.carcinogenic | 254 |
| abstract_inverted_index.colorectal). | 88 |
| abstract_inverted_index.contribution | 46 |
| abstract_inverted_index.cross-cancer | 58 |
| abstract_inverted_index.heritability | 258 |
| abstract_inverted_index.multivariate | 95 |
| abstract_inverted_index.premalignant | 21 |
| abstract_inverted_index.significance | 174 |
| abstract_inverted_index.transmission | 213 |
| abstract_inverted_index.&lt;0.05, | 200 |
| abstract_inverted_index.Meta-analysis | 160 |
| abstract_inverted_index.corresponding | 229 |
| abstract_inverted_index.malignancies. | 42 |
| abstract_inverted_index.&lt;0.05). | 203 |
| abstract_inverted_index.susceptibility | 37, 169, 235 |
| abstract_inverted_index.susceptibility. | 55 |
| abstract_inverted_index.epithelial-based | 31 |
| abstract_inverted_index.gastrointestinal | 5, 32, 163 |
| abstract_inverted_index.MIR1263/LINC01324 | 188 |
| cited_by_percentile_year.max | 94 |
| cited_by_percentile_year.min | 90 |
| corresponding_author_ids | https://openalex.org/A5056062916, https://openalex.org/A5101961565 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 11 |
| corresponding_institution_ids | https://openalex.org/I24943067, https://openalex.org/I4210093194, https://openalex.org/I4210159154 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.800000011920929 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.61615452 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |