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Interactions between vitamin B2, the MTRR rs1801394 and MTR rs1805087 genetic polymorphisms, and colorectal cancer risk in a Korean population
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Madhawa Gunathilake, Minji Kim, Jeonghee Lee, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim
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Epidemiol Health. 2024;46:e2024037. Published online March 11, 2024
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DOI: https://doi.org/10.4178/epih.e2024037
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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.
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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.
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Estimation of heritability attributable to single-locus effects with a regression of offspring on mid-parent (ROMP) method for cardiovascular risk factors.
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Sun Ha Jee, Jung Yong Park, Ji Eun Yoon, Minji Kim, Eun Young Cho, Yang soo Jang
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Korean J Epidemiol. 2003;25(1):24-31.
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PURPOSE
The objective of this study was to estimate the heritability attributable to single-locus effects with a regression of offspring on mid-parent (ROMP) method for cardiovascular risk factors.METHODS The regression of offspring on mid-parent is determined with and without the inclusion of a single-locus effect, and the difference between the slopes of these two regression is an estimate of the heritability attributable to the single-locus effect. The study population included 1,550 family members of 295 patients, derived from cardiovascular genome center. The risk factors considered were total serum cholesterol, triglyceride, LDL cholesterol, apoAI and apoB. Heritability was estimated from the slope of the linear regression of offspring on mid-parents.RESULTS Estimated heritability was 35 to 46% for total cholesterol with 6.2% attributable to polymorphism S128R.
For triglyceride, the estimated heritability was 47.6% with 2% attributable to polymorphism G-217A. The heritability was 36-46% for LDL-cholesterol. For LDL cholesterol, S128R specific effect was 8.7%. Estimated heritability was 62.2% for apoAI with 3.2% attributable to polymorphism G-217A and 58 to 75% for apoB with 5.4% attributable to polymorphism S128R.CONCLUSIONS These traits were significantly associated with polymorphism S128R. These results highlight the importance of considering genetic factors in studies of cardiovascular risk factors. Unlike traditional population-based tests of association, ROMP appears to be robust with respect to population stratification.
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A Review Study on Confounding Effect: Case-control Study.
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Seonwoo Kim, Minji Kim, Soon Young Lee
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Korean J Epidemiol. 1999;21(2):248-253.
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Confounding is the distortion of a disease/exposure association brought about by other factors which are not considered in the study design or the data analysis. These factors are called confounding factors. We should be cautious in data analysis of observational study of association of disease/exposure, since confounding often occurred in observational study. This study examines confounding effect according to data pattern (the ratio of controls to cases, the ratio of exposures to non-exposures for each level of confounding factor), criteria for treating a variable as a confounding variable, and some notes for the analysis in case-control study.
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A Review Study on Comparing Treatment Effects among Subgroups.
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Seonwoo Kim, Minji Kim, Soon Young Lee
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Korean J Epidemiol. 1999;21(1):104-110.
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It is interested in examining treatment effect on a particular category of subjects or in comparing treatment effects among different subgroups as well as overall treatment effect due to heterogeneity of study subjects.
Subgroup analyses are exceedingly common, but they are also often misleading. Conclusions based on subgroup analyses can do harm both when a particular category of people is denied effective treatment (a "false-negative" conclusion), and when ineffective or even harmful treatment is given to a subgroup of people (a "false-positive" conclusion). Because of the frequency and the importance of clinical application of subgroup analysis, researchers need to be cautious about doing subgroup analyses. This study presents guidelines to help conducting subgroup analyses correctly.
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