1.Dietary mercury intake, the IL23R rs10889677 polymorphism, and the risk of gastric cancer in a Korean population: a hospital-based case-control study
Ji Hyun KIM ; Madhawa GUNATHILAKE ; Jeonghee LEE ; Il Ju CHOI ; Young-Il KIM ; Jeongseon KIM
Epidemiology and Health 2024;46(1):e2024051-
OBJECTIVES:
Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract diseases. The aim of this study was to identify the associations between dietary mercury and gastric cancer (GC) and to investigate whether the IL23R rs10889677 polymorphism modifies those associations.
METHODS:
This case-control study included 377 patients with GC and 756 healthy controls. Dietary mercury intake (total mercury and methylmercury) was assessed using a dietary heavy metal database incorporated into the food frequency questionnaire. IL23R genetic polymorphism rs10889677 (A>C) was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models with adjustments for potential confounders.
RESULTS:
A higher dietary methylmercury intake was associated with an elevated risk of GC (OR for the highest vs. lowest tertile [T3 vs. T1], 2.02; 95% CI, 1.41 to 2.91; p for trend <0.001). The IL23R rs10889677 reduced the risk of GC in individuals who carried at least 1 minor allele (OR, 0.62; 95% CI, 0.46 to 0.83; p=0.001; AC/CC vs. AA). Individuals with a C allele exhibited a lower susceptibility to GC through methylmercury intake than those with the AA genotype (OR for the T3 of methylmercury and AA carriers, 2.93; 95% CI, 1.77 to 4.87; and OR for the T3 of methylmercury and AC/CC genotype, 1.30; 95% CI, 0.76 to 2.21; p-interaction=0.013).
CONCLUSIONS
Our findings suggest that a genetic polymorphism, rs10889677 in IL23R, plays a role in modifying the association between dietary methylmercury intake and the risk of GC.
2.Dietary mercury intake, the IL23R rs10889677 polymorphism, and the risk of gastric cancer in a Korean population: a hospital-based case-control study
Ji Hyun KIM ; Madhawa GUNATHILAKE ; Jeonghee LEE ; Il Ju CHOI ; Young-Il KIM ; Jeongseon KIM
Epidemiology and Health 2024;46(1):e2024051-
OBJECTIVES:
Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract diseases. The aim of this study was to identify the associations between dietary mercury and gastric cancer (GC) and to investigate whether the IL23R rs10889677 polymorphism modifies those associations.
METHODS:
This case-control study included 377 patients with GC and 756 healthy controls. Dietary mercury intake (total mercury and methylmercury) was assessed using a dietary heavy metal database incorporated into the food frequency questionnaire. IL23R genetic polymorphism rs10889677 (A>C) was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models with adjustments for potential confounders.
RESULTS:
A higher dietary methylmercury intake was associated with an elevated risk of GC (OR for the highest vs. lowest tertile [T3 vs. T1], 2.02; 95% CI, 1.41 to 2.91; p for trend <0.001). The IL23R rs10889677 reduced the risk of GC in individuals who carried at least 1 minor allele (OR, 0.62; 95% CI, 0.46 to 0.83; p=0.001; AC/CC vs. AA). Individuals with a C allele exhibited a lower susceptibility to GC through methylmercury intake than those with the AA genotype (OR for the T3 of methylmercury and AA carriers, 2.93; 95% CI, 1.77 to 4.87; and OR for the T3 of methylmercury and AC/CC genotype, 1.30; 95% CI, 0.76 to 2.21; p-interaction=0.013).
CONCLUSIONS
Our findings suggest that a genetic polymorphism, rs10889677 in IL23R, plays a role in modifying the association between dietary methylmercury intake and the risk of GC.
3.Dietary mercury intake, the IL23R rs10889677 polymorphism, and the risk of gastric cancer in a Korean population: a hospital-based case-control study
Ji Hyun KIM ; Madhawa GUNATHILAKE ; Jeonghee LEE ; Il Ju CHOI ; Young-Il KIM ; Jeongseon KIM
Epidemiology and Health 2024;46(1):e2024051-
OBJECTIVES:
Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract diseases. The aim of this study was to identify the associations between dietary mercury and gastric cancer (GC) and to investigate whether the IL23R rs10889677 polymorphism modifies those associations.
METHODS:
This case-control study included 377 patients with GC and 756 healthy controls. Dietary mercury intake (total mercury and methylmercury) was assessed using a dietary heavy metal database incorporated into the food frequency questionnaire. IL23R genetic polymorphism rs10889677 (A>C) was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models with adjustments for potential confounders.
RESULTS:
A higher dietary methylmercury intake was associated with an elevated risk of GC (OR for the highest vs. lowest tertile [T3 vs. T1], 2.02; 95% CI, 1.41 to 2.91; p for trend <0.001). The IL23R rs10889677 reduced the risk of GC in individuals who carried at least 1 minor allele (OR, 0.62; 95% CI, 0.46 to 0.83; p=0.001; AC/CC vs. AA). Individuals with a C allele exhibited a lower susceptibility to GC through methylmercury intake than those with the AA genotype (OR for the T3 of methylmercury and AA carriers, 2.93; 95% CI, 1.77 to 4.87; and OR for the T3 of methylmercury and AC/CC genotype, 1.30; 95% CI, 0.76 to 2.21; p-interaction=0.013).
CONCLUSIONS
Our findings suggest that a genetic polymorphism, rs10889677 in IL23R, plays a role in modifying the association between dietary methylmercury intake and the risk of GC.
4.Dietary mercury intake, the IL23R rs10889677 polymorphism, and the risk of gastric cancer in a Korean population: a hospital-based case-control study
Ji Hyun KIM ; Madhawa GUNATHILAKE ; Jeonghee LEE ; Il Ju CHOI ; Young-Il KIM ; Jeongseon KIM
Epidemiology and Health 2024;46(1):e2024051-
OBJECTIVES:
Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract diseases. The aim of this study was to identify the associations between dietary mercury and gastric cancer (GC) and to investigate whether the IL23R rs10889677 polymorphism modifies those associations.
METHODS:
This case-control study included 377 patients with GC and 756 healthy controls. Dietary mercury intake (total mercury and methylmercury) was assessed using a dietary heavy metal database incorporated into the food frequency questionnaire. IL23R genetic polymorphism rs10889677 (A>C) was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models with adjustments for potential confounders.
RESULTS:
A higher dietary methylmercury intake was associated with an elevated risk of GC (OR for the highest vs. lowest tertile [T3 vs. T1], 2.02; 95% CI, 1.41 to 2.91; p for trend <0.001). The IL23R rs10889677 reduced the risk of GC in individuals who carried at least 1 minor allele (OR, 0.62; 95% CI, 0.46 to 0.83; p=0.001; AC/CC vs. AA). Individuals with a C allele exhibited a lower susceptibility to GC through methylmercury intake than those with the AA genotype (OR for the T3 of methylmercury and AA carriers, 2.93; 95% CI, 1.77 to 4.87; and OR for the T3 of methylmercury and AC/CC genotype, 1.30; 95% CI, 0.76 to 2.21; p-interaction=0.013).
CONCLUSIONS
Our findings suggest that a genetic polymorphism, rs10889677 in IL23R, plays a role in modifying the association between dietary methylmercury intake and the risk of GC.
5.Interaction between vitamin E intake and a COMT gene variant on colorectal cancer risk among Korean adults: a case-control study
Shinyoung JUN ; Madhawa GUNATHILAKE ; Jeonghee LEE ; Jae Hwan OH ; Hee Jin CHANG ; Dae Kyung SOHN ; Aesun SHIN ; Jeongseon KIM
Epidemiology and Health 2023;45(1):e2023100-
OBJECTIVES:
Previous human trials have not supported the anticarcinogenic effect of vitamin E despite biological plausibility and considerable epidemiological evidence. A possible explanation for this inconsistency is the interactive effect of the catechol-O-methyltransferase (COMT) gene and supplemental vitamin E on cancer. We examined whether a COMT gene variant modulates the effect of dietary vitamin E intake on colorectal cancer (CRC) risk.
METHODS:
In this case-control study of Korean adults (975 cases and 975 age- and sex-matched controls), dietary vitamin E density (mg/1,000 kcal) was measured using a semiquantitative food frequency questionnaire, COMT single nucleotide polymorphism (SNP) rs740603 (A>G) was genotyped, and CRC was verified histologically. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models with adjustments for potential confounders.
RESULTS:
Higher vitamin E density was associated with a lower risk of CRC (highest vs. lowest quartiles: OR, 0.72; 95% CI, 0.55 to 0.96; p-for-trend=0.002). When stratified by COMT SNP rs740603 genotype, the inverse association between vitamin E density and CRC risk was confined to those with at least 1 A allele (≥median vs.
6.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):191-198
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.
7.Interactions between vitamin B2, the MTRR rs1801394 and MTR rs1805087 genetic polymorphisms, and colorectal cancer risk in a Korean population
Madhawa GUNATHILAKE ; Minji KIM ; Jeonghee LEE ; Jae Hwan OH ; Hee Jin CHANG ; Dae Kyung SOHN ; Aesun SHIN ; Jeongseon KIM
Epidemiology and Health 2024;46(1):e2024037-
OBJECTIVES:
We explored whether the association between vitamin B2 and colorectal cancer (CRC) risk could be modified by the MTRR rs1801394 and MTR rs1805087 genetic polymorphisms and examined whether the interaction effects are sex-specific.
METHODS:
We performed a case-control study involving 1,420 CRC patients and 2,840 controls from the Korea National Cancer Center. Dietary vitamin B2 intake was assessed using a semiquantitative food frequency questionnaire, and the association with CRC was evaluated. Genotyping was performed using an Illumina MEGA-Expanded Array. For gene-nutrient interaction analysis, pre-matched (1,081 patients and 2,025 controls) and matched (1,081 patients and 1,081 controls) subsets were included. Unconditional and conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS:
A higher intake of vitamin B2 was associated with a significantly lower CRC risk (OR, 0.65; 95% CI, 0.51 to 0.82; p<0.001). Carriers of at least 1 minor allele of MTRR rs1801394 showed a significantly higher CRC risk (OR, 1.43; 95% CI, 1.12 to 1.83). Males homozygous for the major allele (A) of MTRR rs1801394 and who had a higher intake of vitamin B2 had a significantly lower CRC risk (OR, 0.31; 95% CI, 0.18 to 0.54; p-interaction=0.02). In MTR rs1805087, males homozygous for the major allele (A) and who had a higher vitamin B2 intake had a significantly lower CRC risk (OR, 0.38; 95% CI, 0.25 to 0.60; p-interaction<0.001).
CONCLUSIONS
The MTRR rs1801394 and MTR rs1805087 genetic polymorphisms may modify the association between vitamin B2 and CRC risk, particularly in males. However, further studies are warranted to confirm these interaction results.
8.Relationship Between Aspirin Use and Site-Specific Colorectal Cancer Risk Among Individuals With Metabolic Comorbidity
Seokyung AN ; Madhawa GUNATHILAKE ; Jeonghee LEE ; Minji KIM ; Jae Hwan OH ; Hee Jin CHANG ; Dae Kyung SOHN ; Aesun SHIN ; Jeongseon KIM
Journal of Korean Medical Science 2024;39(26):e199-
Background:
The relationship between aspirin usage and the risk of colorectal cancer (CRC) among individuals with both hypertension (HTN) and diabetes mellitus (DM) remains unclear. This study aims to explore the impact of aspirin use on the site-specific CRC risk in patients with metabolic comorbidity.
Methods:
A case-control study was conducted among 1,331 CRC patients and 2,771 controls recruited from the Nation Cancer Center in Korea. Multinomial logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between aspirin use, metabolic disease status, and site-specific CRC risk.
Results:
Among the 4,102 participants, 1,191 individuals had neither HTN nor DM, 2,044 were diagnosed with HTN, 203 with DM, and 664 presented with HTN and DM comorbidity.An increasing number of HTN and DM was associated with an increased risk of overall CRC (HTN or DM: OR, 1.70; 95% CI, 1.39–2.07; HTN and DM: OR, 8.43; 95% CI, 6.37–11.16), while aspirin use was associated with a decreased risk of overall CRC (OR, 0.31; 95% CI, 0.21–0.46).These results remained consistent across anatomical sites. Among individuals with HTN and DM comorbidity, aspirin use notably associated with lower risk of overall CRC (OR, 0.39; 95% CI, 0.21–0.72), proximal colon (OR, 0.32; 95% CI, 0.13–0.71) and rectal cancer (OR, 0.27;95% CI, 0.08–0.97), but not distal colon cancer (OR, 0.58; 95% CI, 0.27–1.24).
Conclusion
This study showed that aspirin use is negatively associated with overall and sitespecific CRC, even among individuals with HTN and DM comorbidity.
9.Fecal Microbial Dysbiosis Is Associated with Colorectal Cancer Risk in a Korean Population
Jeongseon KIM ; Madhawa GUNATHILAKE ; Hyun Yang YEO ; Jae Hwan OH ; Byung Chang KIM ; Nayoung HAN ; Bun KIM ; Hyojin PYUN ; Mi Young LIM ; Young-Do NAM ; Hee Jin CHANG
Cancer Research and Treatment 2025;57(1):198-211
Purpose:
The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking.
Materials and Methods:
In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2.
Results:
There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples.
Conclusion
Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.
10.Fecal Microbial Dysbiosis Is Associated with Colorectal Cancer Risk in a Korean Population
Jeongseon KIM ; Madhawa GUNATHILAKE ; Hyun Yang YEO ; Jae Hwan OH ; Byung Chang KIM ; Nayoung HAN ; Bun KIM ; Hyojin PYUN ; Mi Young LIM ; Young-Do NAM ; Hee Jin CHANG
Cancer Research and Treatment 2025;57(1):198-211
Purpose:
The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking.
Materials and Methods:
In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2.
Results:
There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples.
Conclusion
Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.