Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population: Hyojin Pyun, Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Joohon Sung, Jeongseon Kim; Cancer Res Treat. 2024;56(1):191-198. Published online June 20, 2023; DOI: https://doi.org/10.4143/crt.2022.958

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Purpose
We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns.
Materials and Methods
The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed.
Results
In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10^–83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10^–6 (0.05/13,114); DEFB108B had the lowest p=5.94×10^–15, followed by FAM86C1 (p=1.74×10^–14), PSCA (p=1.81×10^–14), and KLHDC4 (p=5.00×10^–10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway.
Conclusion
While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.

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Investigating the Shared Genetic Architecture Between Leukocyte Telomere Length and Prostate Cancer
Zhizhou Li, Maoyu Wang, Shuxiong Zeng, Ziwei Wang, Yidie Ying, Qing Chen, Chen Zhang, Wei He, Chaoyang Sheng, Yi Wang, Zhensheng Zhang, Chuanliang Xu, Huiqing Wang
The World Journal of Men's Health.2024;[Epub] CrossRef

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Pediatric cancer

Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma: Ji Won Lee, Joon Seol Bae, Jin Ho Kim, Hee Won Cho, Hee Young Ju, Keon Hee Yoo, Hong Hoe Koo, Sook-young Woo, Seonwoo Kim, Ki Woong Sung; Cancer Res Treat. 2022;54(1):259-268. Published online April 12, 2021; DOI: https://doi.org/10.4143/crt.2021.010

Abstract PDF Supplementary Material PubReader ePub

Purpose
We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma.
Materials and Methods
The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed.
Results
An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC.
Conclusion
In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

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Impact of 10% Dose Reductions and Duration of Treatment Delays in the Management of Chemotherapy‐Induced Neutropenia in Dogs Treated With Common Chemotherapy Protocols: A Single‐Centre Experience
Suzanne Busser, Laura Blackwood, Constanza Pereira, Margo Chase‐Topping, Spela Bavcar, Quentin Fournier
Veterinary and Comparative Oncology.2024; 22(4): 542. CrossRef
Targeting the myeloid microenvironment in neuroblastoma
Marjolein C. Stip, Loes Teeuwen, Miranda P. Dierselhuis, Jeanette H. W. Leusen, Daniëlle Krijgsman
Journal of Experimental & Clinical Cancer Research.2023;[Epub] CrossRef

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Genome-Wide Association of Genetic Variation in the PSCA Gene with Gastric Cancer Susceptibility in a Korean Population: Boyoung Park, Sarah Yang, Jeonghee Lee, Hae Dong Woo, Il Ju Choi, Young Woo Kim, Keun Won Ryu, Young-Il Kim, Jeongseon Kim; Cancer Res Treat. 2019;51(2):748-757. Published online September 5, 2018; DOI: https://doi.org/10.4143/crt.2018.162

Abstract PDF Supplementary Material PubReader ePub

Purpose
Half of the world’s gastric cancer cases and the highest gastric cancer mortality rates are observed in Eastern Asia. Although several genome-wide association studies (GWASs) have revealed susceptibility genes associated with gastric cancer, no GWASs have been conducted in the Korean population, which has the highest incidence of gastric cancer.
Materials and Methods
We performed genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and 3,693 healthy controls.
Results
We showed that the rs2976394 in the prostate stem cell antigen (PSCA) gene is a gastriccancer-susceptibility gene in a Korean population, with genome-wide significance and an odds ratio (OR) of 0.70 (95% confidence interval [CI], 0.64 to 0.77). A strong linkage disequilibrium with rs2294008 was also found, indicating an association with susceptibility. Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold lower risk of gastric cancer compared to those with the TT genotype (OR, 0.47; 95% CI, 0.39 to 0.57). The effect of the PSCA gene on gastric cancer was more prominent in the female population and for diffuse type gastric cancer.
Conclusion
Our result confirmed that the PSCA gene may be the most important susceptibility gene for gastric cancer risk in a Korean population.

Citations

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Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population
Hyojin Pyun, Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Joohon Sung, Jeongseon Kim
Cancer Research and Treatment.2024; 56(1): 191. CrossRef
HiChIP-Based Epigenomic Footprinting Identifies a Promoter Variant of UXS1 That Confers Genetic Susceptibility to Gastroesophageal Cancer
Ansley Gnanapragasam, Eftyhios Kirbizakis, Anna Li, Kyle H. White, Katelyn L. Mortenson, Juliana Cavalcante de Moura, Wajih Jawhar, Yifei Yan, Reilly Falter, Colleen Russett, Betty Giannias, Sophie Camilleri-Broët, Nicholas Bertos, Jonathan Cools-Lartigue
Cancer Research.2024; 84(14): 2377. CrossRef
High Polygenic Risk Scores Positively Associated with Gastric Cancer Risk Interact with Coffee and Polyphenol Intake and Smoking Status in Korean Adults
Meiling Liu, Sang-Shin Song, Sunmin Park
Nutrients.2024; 16(19): 3263. CrossRef
Interaction between dietary potassium intake and TNF-α rs1800629 genetic polymorphism in gastric cancer risk: a case–control study conducted in Korea
Tao Thi Tran, Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Jeongseon Kim
British Journal of Nutrition.2023; 130(5): 887. CrossRef
Rare variants confer shared susceptibility to gastrointestinal tract cancer risk
Ji Zheng, Xin Wang, Jingrao Li, Yuanna Wu, Jiang Chang, Junyi Xin, Meilin Wang, Tianpei Wang, Qingyi Wei, Mengyun Wang, Ruoxin Zhang
Frontiers in Oncology.2023;[Epub] CrossRef
The association of dietary fibre intake and the IL13 rs20541 polymorphism with the risk of gastric cancer: a case-control study in Korea
Tao Thi Tran, Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Jeongseon Kim
European Journal of Clinical Nutrition.2022; 76(7): 1031. CrossRef
Systematic review of gastric cancer-associated genetic variants, gene-based meta-analysis, and gene-level functional analysis to identify candidate genes for drug development
Sangjun Lee, Han-Kwang Yang, Hyuk-Joon Lee, Do Joong Park, Seong-Ho Kong, Sue K. Park
Frontiers in Genetics.2022;[Epub] CrossRef
Incidence of Hereditary Gastric Cancer May Be Much Higher than Reported
Paula Baraúna de Assumpção, Paulo Pimentel de Assumpção, Fabiano Cordeiro Moreira, Ândrea Ribeiro-dos-Santos, Amanda F. Vidal, Leandro Magalhães, André Salim Khayat, André Maurício Ribeiro-dos-Santos, Giovanna C. Cavalcante, Adenilson Leão Pereira, Inácio
Cancers.2022; 14(24): 6125. CrossRef
Enhancing the Trajectories of Cancer Health Disparities Research: Improving Clinical Applications of Diversity, Equity, Inclusion, and Accessibility
Rachel Martini, Endale Gebregzabher, Lisa Newman, Melissa B. Davis
Cancer Discovery.2022; 12(6): 1428. CrossRef
Identification of Novel Susceptible Genes of Gastric Cancer Based on Integrated Omics Data
Huang Yaoxing, Yu Danchun, Sun Xiaojuan, Jiang Shuman, Yan Qingqing, Jia Lin
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
The Associations of Dietary Iron Intake and the Transferrin Receptor (TFRC) rs9846149 Polymorphism with the Risk of Gastric Cancer: A Case–Control Study Conducted in Korea
Tao Thi Tran, Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Jeongseon Kim
Nutrients.2021; 13(8): 2600. CrossRef
Integration of GWAS and eQTL Analysis to Identify Risk Loci and Susceptibility Genes for Gastric Cancer
Jing Ni, Bin Deng, Meng Zhu, Yuzhuo Wang, Caiwang Yan, Tianpei Wang, Yaqian Liu, Gang Li, Yanbing Ding, Guangfu Jin
Frontiers in Genetics.2020;[Epub] CrossRef
Evolutionary History of the Risk of SNPs for Diffuse-Type Gastric Cancer in the Japanese Population
Risa L. Iwasaki, Koji Ishiya, Hideaki Kanzawa-Kiriyama, Yosuke Kawai, Jun Gojobori, Yoko Satta
Genes.2020; 11(7): 775. CrossRef
TNF genetic polymorphism (rs1799964) may modify the effect of the dietary inflammatory index on gastric cancer in a case–control study
Jeeeun Kim, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Joohon Sung, Jeongseon Kim
Scientific Reports.2020;[Epub] CrossRef
Prediction of gastric cancer risk: association between ZBTB20 genetic variance and gastric cancer risk in Chinese Han population
Fei Bai, Ke Xiao
Bioscience Reports.2020;[Epub] CrossRef
Incidence of Stomach and Esophageal Cancers in Mongolia: Data from 2009 to 2018
Tsegmed Sambuu, Nasanjargal Tumurbat, Bayar Davaa, Bolor-Erdene Tudev
Euroasian Journal of Hepato-Gastroenterology.2020; 10(1): 16. CrossRef

10,108 View
207 Download
16 Web of Science
16 Crossref

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