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3 "Madhawa Gunathilake"
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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
Epidemiol Health. 2024;46:e2024051.   Published online May 21, 2024
DOI: https://doi.org/10.4178/epih.e2024051
  • 1,868 View
  • 54 Download
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
Mercury can stimulate immune responses through T helper 17 (Th17). The gene <i>IL23R</i> 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 <i>IL23R</i> 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. <i>IL23R</i> 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 [T<sub>3</sub> vs. T<sub>1</sub>], 2.02; 95% CI, 1.41 to 2.91; p for trend <0.001). The <i>IL23R</i> 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 T<sub>3</sub> of methylmercury and AA carriers, 2.93; 95% CI, 1.77 to 4.87; and OR for the T<sub>3</sub> 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 <i>IL23R</i>, plays a role in modifying the association between dietary methylmercury intake and the risk of GC.
Summary
Korean summary
본 연구는 식이 수은과 위암 간의 연관성을 탐색하고, microRNA-lethal-7의 예측된 결합 부위 내에 위치한 IL23R rs10889677 다형성이 이러한 연관성에 영향을 미칠 수 있는지 규명하고자 합니다. 식이 메틸수은 섭취량에 비례하여 위암 발생 위험이 증가하는 경향이 확인되었고, IL23R rs10889677 다형성은 식이 메틸수은으로 의한 위암 발생 위험을 조절하는 인자로 작용할 수 있음을 시사합니다.
Key Message
This study aimed to investigate the associations between dietary mercury and gastric cancer (GC) and to determine whether the IL23R rs10889677 polymorphism, located within a predicted binding site for microRNA-lethal-7, may modify these associations. A higher dietary methylmercury intake was associated with an increased risk of GC, while the IL23R rs10889677 polymorphism may modify the detrimental effect of dietary methylmercury on gastric carcinogenesis.
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
Epidemiol Health. 2024;46:e2024037.   Published online March 11, 2024
DOI: https://doi.org/10.4178/epih.e2024037
  • 3,066 View
  • 118 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
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.
Summary
Korean summary
본 연구는 환자-대조군 연구를 통해 비타민 B2 섭취와 대장암 발생의 관련성을 조사하고, 대장암 발생에 있어 methionine synthase (MTRR) rs1801394 및 methionine synthase reductase (MTR) rs1805087의 유전적 다형성과 식이 요인간에 상호작용을 알아보고자 한다. 비타민 B2 의 섭취는 대장암 발생의 위험도를 낮추는 것으로 나타났으며 특히, 남성의 경우 대장암 발생의 위험도가 MTRR rs1801394 및 MTR rs1805087의 유전자형과 식이 섭취에 따른 상호 관련성에 의해 영향을 받는 것으로 나타났다.
Key Message
We conducted a case-control study to observe the association between vitamin B2 intake and the risk of colorectal cancer (CRC), and to determine whether this association could be modified by the methionine synthase (MTRR) rs1801394 and methionine synthase reductase (MTR) rs1805087 genetic polymorphisms. Higher intake of vitamin B2 is a protective factor in lowering CRC risk, and rs1801394 of MTRR and rs1805087 of MTR may particularly modify this association in males.

Citations

Citations to this article as recorded by  
  • Genetic variants in folate metabolism-related genes, serum folate and hepatocellular carcinoma survival: the Guangdong Liver Cancer Cohort study
    Yunshan Li, Jing Shu, Peishan Tan, Xiaocong Dong, Mingjie Zhang, Tongtong He, Zhijun Yang, Xuehong Zhang, Edward L. Giovannucci, Zhaoyan Liu, Zhongguo Zhou, Qijiong Li, Yanjun Xu, Xiaojun Xu, Tianyou Peng, Jialin Lu, Yaojun Zhang, Huilian Zhu, Aiping Fang
    British Journal of Nutrition.2024; : 1.     CrossRef
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
Epidemiol Health. 2023;45:e2023100.   Published online November 14, 2023
DOI: https://doi.org/10.4178/epih.e2023100
  • 4,083 View
  • 128 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
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. <median: OR, 0.63; 95% CI, 0.51 to 0.78). The interaction between rs740603 and vitamin E density was significant (p-for-interaction=0.020). No direct association was observed between COMT SNP rs740603 and CRC risk (OR, 1.08; 95% CI, 0.83 to 1.41).
CONCLUSIONS
Our findings support a role for a genetic polymorphism in COMT in modifying the association between dietary vitamin E intake and CRC.
Summary
Korean summary
본 연구는 국립암센터에서 수집한 대장암 환자-대조군 자료를 활용하여, catechol-O-methyltransferase (COMT) 유전자의 단일염기다형성(SNP)에 따라 비타민 E 섭취와 대장암 위험 간의 연관성이 달라지는지 파악하고자 하였다. 분석 결과, COMT SNP rs740603의 유전자형에 따라 식이를 통한 비타민 E 섭취 밀도와 대장암 위험 간의 연관성이 다르게 나타나 COMT 유전자와 비타민 E 섭취 간의 상호작용이 대장암 발생 위험에 영향을 미칠 가능성이 있음을 제시하였다.
Key Message
In this case-control study of Korean adults, we examined whether a polymorphism in the catechol-O-methyltransferase (COMT) gene modulates the effect of dietary vitamin E intake on colorectal cancer risk. Our results suggest that the inverse association between vitamin E density and colorectal cancer risk is confined to carriers of the COMT rs740603 A allele. The findings of our study support the interactive effect of the COMT gene and vitamin E intake on colorectal cancer risk.

Citations

Citations to this article as recorded by  
  • The Role of Dietary Vitamins and Antioxidants in Preventing Colorectal Cancer: A Systematic Review
    Mohammed Ajebli, Christopher R Meretsky, Mourad Akdad, Ayoub Amssayef, Morad Hebi
    Cureus.2024;[Epub]     CrossRef

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