Cancer Research and Treatment

Original Articles

Smoking, Alcohol, and Abdominal Obesity Increase Gastric Cancer Risk after Helicobacter pylori Eradication: Joo Hyun Lim, Cheol Min Shin, Kyungdo Han, Jin-Hyung Jung, Jinju Choi, Eun Hyo Jin, Seung Joo Kang, Dong Ho Lee; Received November 3, 2025 Accepted December 30, 2025 Published online January 2, 2026; DOI: https://doi.org/10.4143/crt.2025.1200 [Accepted]

Abstract PDF: Purpose
Helicobacter pylori is the single most important risk factor for gastric cancer (GC). However, H. pylori eradication (HPE) does not eliminate risk of GC. To clarify the association of lifestyle factors with GC risk after HPE.
Materials and Methods
Using the Korean National Health Insurance Services (NHIS) database, adult individuals who claimed HPE between 2010 and 2016 were analyzed. The adjusted hazard ratios (aHR) for GC were analyzed according to the lifestyle status including smoking (never; light [<10PY]; moderate [10-20PY]; heavy [≥20PY]), alcohol (none; mild [<30g/day]; heavy [30g/day]), and abdominal obesity by using Cox proportional hazard model.
Results
During a median follow-up period of 6.7 years, 9,754 individuals were newly diagnosed with GC among the total of 1,282,702 subjects. Compared with never smokers, moderate (aHR 1.12 [95%CI 1.04-1.20]) and heavy smokers (1.34 [1.27-1.42]) had greater risks of post-HPE GC with dose-response manner. Heavy drinkers had increased risk of GC (1.23 [1.15-1.32]) compared with non-drinkers, and those with abdominal obesity had slightly elevated GC risk compared with those without that (1.11 [1.06-1.15]). In subgroup analyses, those who had HPE at age ≥ 55 were shown to be more affected by the unhealthy lifestyles (smoking [p-for-interaction <0.01], alcohol [0.03], and abdominal obesity [0.03]). Also, male showed greater risk increase by smoking habit [p-for-interaction 0.02] than female.
Conclusion
Unhealthy lifestyles like smoking, alcohol, and abdominal obesity were shown as risk factors for post-HPE GC. Those with late HPE were more likely to be affected by unhealthy lifestyles.

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Clinicopathological Factors Influencing PD-L1 Expression and The Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea: Jeong hwan Lee, Nayoung Kim, Ji-Hyun Kim, Hyeon Jeong Oh, Yeejin Kim, Yonghoon Choi, Hyemin Jo, Ho-Kyoung Lee, Jinju Choi, Yu Kyung Jun, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, Hye Seung Lee, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Yoon Jin Lee, Kyoung Ho Lee, Young Hoon Kim, Soyeon Ahn; Received January 31, 2025 Accepted August 5, 2025 Published online August 13, 2025; DOI: https://doi.org/10.4143/crt.2025.126 [Accepted]

Abstract PDF: Purpose
Programmed cell death ligand-1 (PD-L1) negatively regulates T-cell activation, and exhibits sex-based differences in expression and immune responses. This study investigated sex-related differences in clinicopathological factors influencing PD-L1 expression and the effect of immune checkpoint inhibitors (ICIs) on survival in gastric cancer (GC) patients in South Korea.
Materials and Methods
We analyzed a prospective cohort of 468 GC patients who underwent PD-L1 immunohistochemistry. Age, tumor characteristics, molecular features, and survival outcomes were compared by sex. Multivariate analyses, including Cox proportional hazards modeling with an interaction term for sex, were performed.
Results
Among 468 patients, 280 (59.8%) were PD-L1 positive. In the overall cohort, PD-L1 positivity was significantly associated with Epstein-BarrVirus (EBV) infection (odd ratio [OR]=7.46, p<0.001), antral location of GC (OR=1.84, p=0.027), and macrosatellite instability-High (MSI-H) (OR=5.04, p=0.027). Diffuse-type histology was inversely associated (OR=0.22, p=0.041). In males, EBV (OR=36.27) and antral location (OR=2.38) were significant. In females, only MSI-H was significant (OR=11.63). ICI-containing therapy significantly improved survival in males (p=0.012) but not in females (p=0.415). Cox regression showed a survival benefit from ICIs (HR=0.70, p=0.080), with a borderline-significant interaction by sex (p=0.073).
Conclusion
PD-L1 expression and therapeutic efficacy of ICIs differ by sex in GC. EBV infection and antral tumor location were independent factors in males, while MSI-H status was significant in females. These findings highlights the importance of sex-based immunobiology in tailoring GC treatment strategies.

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Microbial Dynamics Across Molecular Subtypes and Prognostic Significance of Lactobacillus in Gastric Cancer: Soo Kyung Nam, Juhyeong Park, Sujin Oh, Yoonjin Kwak, Cheol Min Shin, Kyoung Un Park, Nak-Jung Kwon, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee; Received April 25, 2025 Accepted July 16, 2025 Published online July 17, 2025; DOI: https://doi.org/10.4143/crt.2025.449 [Accepted]

Abstract PDF: Purpose
Recent studies have revealed a diverse gastric microbiota beyond Helicobacter pylori, suggesting a role in gastric cancer (GC). We aimed to investigate the composition and characteristics of the microbiota in GC and non-cancerous gastric mucosa (NC), with a particular focus on their relationship to molecular subtypes.
Materials and Methods
We conducted 16S rRNA sequencing and whole transcriptomic analysis on fresh-frozen GC and NC tissue samples from 192 GC patients, as well as saliva samples from 12 GC patients and 18 healthy individuals. Microsatellite instability (MSI), Epstein-Barr virus (EBV) in situ hybridization, and immunohistochemistry for p53 and E-cadherin were used to define molecular subtypes.
Results
GC tissues exhibited significantly higher diversity compared to matched NC tissues, with microbial profiles marked by decreased Helicobacter and increased Streptococcus, Prevotella, and Lactobacillus. Saliva samples predominantly contained oral bacteria and exhibited distinct microbial profiles from gastric tissues. In GC tissue, Helicobacter abundance was negatively correlated with key immune checkpoint genes (CTLA-4, PDCD1, CD274, and LAG3), whereas Prevotella, Streptococcus, and Fusobacterium were positively correlated. MSI-high and EBV-positive subtypes showed lower levels of Helicobacter but higher levels of Lactobacillus, Prevotella, and Streptococcus compared to the epithelial-mesenchymal transition (EMT)-like subtype. Notably, within MSI-H GC, a subgroup characterized by Lactobacillus-enriched and otherwise microbiota-depleted profiles was significantly associated with poorer overall and disease-free survival.
Conclusion
These findings underscore distinct microbial patterns across GC molecular subtypes, suggesting potential biomarkers for GC diagnosis and treatment.

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Discrepancy between Genetically Predicted and Observed Alcohol Intake and Its Impact on Gastric Cancer Susceptibility: Ga-Eun Yie, Cheol Min Shin, Kyungtaek Park, Jinyeon Jo, Ah Ra Do, Sungkyoung Choi, Jung Hun Ohn, Sejoon Lee, Jeongseon Kim, Sun Ha Jee, Seung Joo Kang, Nayoung Kim, Sungho Won; Received January 24, 2025 Accepted May 29, 2025 Published online May 30, 2025; DOI: https://doi.org/10.4143/crt.2025.109 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
We aimed to investigate how genetic predisposition to drinking and gastric cancer (GC) modifies the association between alcohol consumption and GC risk in the Korean population.
Materials and Methods
Polygenic risk scores for GC (PRS-GC) and alcohol consumption (PRS-Alcohol) were formulated using genome-wide association results from BioBank Japan. Validation was performed using Korean cohorts (SNUBH-GENIE cohort), incorporating 8,846 controls and 531 patients with GC. Subsequently, these PRSs were applied to an independent Korean cohort of 67,771 participants, including 313 patients with GC during the follow-up for 14 years (KoGES cohort).
Results
In KoGES cohort, the influence of alcohol consumption on GC risk was significantly altered by the PRS-GC and exhibited a synergistic interaction effect. PRS-Alcohol itself shows a negative correlation with GC risk. However, when actual alcohol consumption significantly exceeded genetically predicted levels, the risk of alcohol-related GC was notably increased (adjusted hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.72). Heavy drinkers in the high–PRS-GC/low–PRS-Alcohol group had a 2.16 times higher risk of GC than non-to-light drinkers, which was prominent in males.
Conclusion
Korean drinkers with higher PRS-GC who consume alcohol more than genetically predicted levels are susceptible to GC. PRS-GC and PRS-Alcohol may be beneficial for assessing the impact of alcohol consumption on GC risk in Koreans.

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Gastrointestinal cancer

Survival Rates of Patients with Gastric Cancer According to Age and Sex: A Large-Scale Study Using Data from 14,739 Patients: Yonghoon Choi, Nayoung Kim, Ji Hyun Kim, Hyeong Ho Jo, Hyeon Jeong Oh, Hye Seung Lee, Yu Kyung Jun, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Yoon Jin Lee, Kyoung Ho Lee, Young Hoon Kim; Cancer Res Treat. 2026;58(1):252-263. Published online April 16, 2025; DOI: https://doi.org/10.4143/crt.2025.149

Abstract PDF Supplementary Material PubReader ePub: Purpose
The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex.
Materials and Methods
Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed.
Results
Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males.
Conclusion
Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

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The Persistence of Hypertriglyceridemia and the Risk of Early Onset Colorectal Cancer According to Tumor Subsites: A Nationwide Population-Based Study: Young Hoon Chang, Cheol Min Shin, Kyungdo Han, Jin Hyung Jung, Eun Hyo Jin, Joo Hyun Lim, Seung Joo Kang, Yoon Jin Choi, Hyuk Yoon, Young Soo Park, Nayoung Kim, Dong Ho Lee; Cancer Res Treat. 2024;56(3):825-837. Published online December 20, 2023; DOI: https://doi.org/10.4143/crt.2023.753

Abstract PDF Supplementary Material PubReader ePub

Purpose
The incidence of early-onset colorectal cancer (EoCRC) is increasing worldwide. The association between hypertriglyceridemia (HTG) and EoCRC risk remains unclear.
Materials and Methods
We conducted a nationwide cohort study of 3,340,635 individuals aged 20-49 years who underwent health checkups between 2009 and 2011 under the Korean National Health Insurance Service. HTG was defined as serum triglyceride (TG) level ≥ 150 mg/dL. According to the change in TG status, participants were categorized into persistent normotriglyceridemia (NTG; group 1), NTG to HTG (group 2), HTG to NTG (group 3), and persistent HTG (group 4) groups. The EoCRC incidence was followed up until 2019.
Results
In total, 7,492 EoCRC cases developed after a mean of 6.05 years of follow-up. Group 4 had the highest risk of EoCRC (adjusted hazard ratio [aHR], 1.097; 95% confidence interval [CI], 1.025 to 1.174). While the risk of rectal cancer was significantly increased in groups 3 and 4 (aHR [95% CI], 1.236 [1.076 to 1.419] and 1.175 [1.042-1.325], respectively), no significant risk differences were observed in right colon cancer. In group 4, male sex and diabetes were associated with a further increased risk of EoCRC (aHR [95% CI], 1.149 [1.082 to 1.221] and 1.409 [1.169 to 1.699], respectively). In addition, there was a dose-response relationship between serum TG levels and the risk of EoCRC (p for trends < 0.0001).
Conclusion
Persistent HTG increased the risk of EoCRC, which was significantly higher only for rectal cancer and marginally higher for other colonic subsites.

Citations

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Systemic inflammation mediates the link between metabolic syndrome and colorectal cancer risk: insights from a large prospective cohort
Wenwen Lv, Suna Wang, Lei Duan, Zhongxun Dong, Hai Zhu, Gang Wang, Zhangsheng Yu, Shuhua Xu
Postgraduate Medical Journal.2026;[Epub] CrossRef
The multifaceted role of agents counteracting metabolic syndrome: A new hope for gastrointestinal cancer therapy
Elena Crecca, Gianfranco Di Giuseppe, Claudia Camplone, Virginia Vigiano Benedetti, Ombretta Melaiu, Teresa Mezza, Chiara Cencioni, Francesco Spallotta
Pharmacology & Therapeutics.2025; 270: 108847. CrossRef
Obesity-Associated Colorectal Cancer
Lucia Gonzalez-Gutierrez, Omar Motiño, Daniel Barriuso, Juan de la Puente-Aldea, Lucia Alvarez-Frutos, Guido Kroemer, Roberto Palacios-Ramirez, Laura Senovilla
International Journal of Molecular Sciences.2024; 25(16): 8836. CrossRef

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Development and Validation of Models to Predict Lymph Node Metastasis in Early Gastric Cancer Using Logistic Regression and Gradient Boosting Machine Methods: Hae Dong Lee, Kyung Han Nam, Cheol Min Shin, Hye Seung Lee, Young Hoon Chang, Hyuk Yoon, Young Soo Park, Nayoung Kim, Dong Ho Lee, Sang-Hoon Ahn, Hyung-Ho Kim; Cancer Res Treat. 2023;55(4):1240-1249. Published online March 21, 2023; DOI: https://doi.org/10.4143/crt.2022.1330

Abstract PDF Supplementary Material PubReader ePub

Purpose
To identify important features of lymph node metastasis (LNM) and develop a prediction model for early gastric cancer (EGC) using a gradient boosting machine (GBM) method.
Materials and Methods
The clinicopathologic data of 2556 patients with EGC who underwent gastrectomy were used as training set and the internal validation set (set 1) at a ratio of 8:2. Additionally, 548 patients with EGC who underwent endoscopic submucosal dissection (ESD) as the initial treatment were included in the external validation set (set 2). The GBM model was constructed, and its performance was compared with that of the Japanese guidelines.
Results
LNM was identified in 12.6% (321/2556) of the gastrectomy group (training set & set 1) and 4.3% (24/548) of the ESD group (set 2). In the GBM analysis, the top five features that most affected LNM were lymphovascular invasion, depth, differentiation, size, and location. The accuracy, sensitivity, specificity, and the area under the receiver operating characteristics of set 1 were 0.566, 0.922, 0.516, and 0.867, while those of set 2 were 0.810, 0.958, 0.803, and 0.944, respectively. When the sensitivity of GBM was adjusted to that of Japanese guidelines (beyond the expanded criteria in set 1 [0.922] and eCuraC-2 in set 2 [0.958]), the specificities of GBM in sets 1 and 2 were 0.516 (95% confidence interval, 0.502-0.523) and 0.803 (0.795-0.805), while those of the Japanese guidelines were 0.502 (0.488-0.509) and 0.788 (0.780-0.790), respectively.
Conclusion
The GBM model showed good performance comparable with the eCura system in predicting LNM risk in EGCs.

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npj Digital Medicine.2025;[Epub] CrossRef
The artificial intelligence revolution in gastric cancer management: clinical applications
Runze Li, Jingfan Li, Yuman Wang, Xiaoyu Liu, Weichao Xu, Runxue Sun, Binqing Xue, Xinqian Zhang, Yikun Ai, Yanru Du, Jianming Jiang
Cancer Cell International.2025;[Epub] CrossRef
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Qian Li, Shangcheng Yan, Weiran Yang, Zhuan Du, Ming Cheng, Renwei Chen, Qiankun Shao, Yuan Tian, Mengchao Sheng, Wei Peng, Yongyou Wu
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Aberrant DNA Methylation Maker for Predicting Metachronous Recurrence After Endoscopic Resection of Gastric Neoplasms: Cheol Min Shin, Nayoung Kim, Hyuk Yoon, Yoon Jin Choi, Ji Hyun Park, Young Soo Park, Dong Ho Lee; Cancer Res Treat. 2022;54(4):1157-1166. Published online January 18, 2022; DOI: https://doi.org/10.4143/crt.2021.997

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate whether MOS methylation can be useful for the prediction of metachronous recurrence after endoscopic resection of gastric neoplasms.
Materials and Methods
From 2012 to 2017, 294 patients were prospectively enrolled after endoscopic resection of gastric dysplasia (n=171) or early gastric cancer (n=123). When Helicobacter pylori was positive, eradication therapy was performed. Among them, 124 patients completed the study protocol (follow-up duration > 3 years or development of metachronous recurrence during the follow-up). Methylation levels of MOS were measured at baseline using quantitative MethyLight assay from the antrum.
Results
Median follow-up duration was 49.9 months. MOS methylation levels at baseline were not different by age, sex, and current H. pylorii infection, but they showed a weak correlation with operative link on gastritis assessment (OLGA) or operative link on gastric intestinal metaplasia assessment (OLGIM) stages (Spearman’s ρ=0.240 and 0.174, respectively; p < 0.05). During the follow-up, a total of 20 metachronous gastric neoplasms (13 adenomas and 7 adenocarcinomas) were developed. Either OLGA or OLGIM stage was not useful in predicting the risk for metachronous recurrence. In contrast, MOS methylation high group (≥ 34.82%) had a significantly increased risk for metachronous recurrence compared to MOS methylation low group (adjusted hazard ratio, 4.76; 95% confidence interval, 1.54 to 14.79; p=0.007).
Conclusion
MOS methylation can be a promising marker for predicting metachronous recurrence after endoscopic resection of gastric neoplasms. To confirm the usefulness of MOS methylation, validation studies are warranted in the future (ClinicalTrials No. NCT04830618).

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Association between the Persistence of Obesity and the Risk of Gastric Cancer: A Nationwide Population-Based Study: Joo Hyun Lim, Cheol Min Shin, Kyung-Do Han, Seung Woo Lee, Eun Hyo Jin, Yoon Jin Choi, Hyuk Yoon, Young Soo Park, Nayoung Kim, Dong Ho Lee; Cancer Res Treat. 2022;54(1):199-207. Published online May 4, 2021; DOI: https://doi.org/10.4143/crt.2021.130

Abstract PDF Supplementary Material PubReader ePub

Purpose
There remains controversy about relationship between obesity and gastric cancer. We aimed to examine the association using obesity-persistence.
Materials and Methods
We analyzed a nationwide population-based cohort which underwent health check-up between 2009 and 2012. Among them, those who had annual examinations during the last 5 years were selected. Gastric cancer risk was compared between those without obesity during the 5 years (never-obesity group) and those with obesity diagnosis during the 5 years (non-persistent obesity group; persistent obesity group).
Results
Among 2,757,017 individuals, 13,441 developed gastric cancer after median 6.78 years of follow-up. Gastric cancer risk was the highest in persistent obesity group (incidence rate [IR], 0.89/1,000 person-years; hazard ratio [HR], 1.197; 95% confidence interval [CI], 1.117 to 1.284), followed by non-persistent obesity group (IR, 0.83/1,000 person-years; HR, 1.113; 95% CI, 1.056 to 1.172) compared with never-obesity group. In subgroup analysis, this positive relationship was true among those < 65 years old and male. Among heavy-drinkers, the impact of obesity-persistence on the gastric cancer risk far increased (non-persistent obesity: HR, 1.297; 95% CI, 1.094 to 1.538; persistent obesity: HR, 1.351; 95% CI, 1.076 to 1.698).
Conclusion
Obesity-persistence is associated with increased risk of gastric cancer in a dose-response manner, especially among male < 65 years old. The risk raising effect was much stronger among heavy-drinkers.

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