Epidemiology and Health

Original Articles

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

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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.

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

The Role of Genetic Polymorphism of Cytochrome P450 2E1 in Bladder Cancer in Korea.: Jiyeob Choi, Seungjoon Lee, Kyoungmu Lee, Inmi Choi, Youngju Lee, Hyungjune Im, Sang Yun Lee, Kijung Yoon, Sooung Kim, Moonsoo Park, Hanyong Choi, Whang Choi, Keunyoung Yoo, Soohun Cho, Daehee Kang; Korean J Epidemiol. 2000;22(1):59-67.

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Abstract PDF: Abstract
Although the association of genetic polymorphisms in glutathione S-transferase(GST) and N-acetyltransferase(NAT) with bladder cancer has been reported, limited numbers of studies have been indicated the association of CYP2E1 with bladder cancer, particularly in Asian population. A hospital based case-control study was conducted in South Korean, consisting of 232 histologically confirmed prevalent bladder cancer cases and 165 controls to evaluate the association between genetic polymorphisms of CYP2E1(RsaI) and development of bladder cancer. The frequency of CYP2E1(RsaI) c1/c1 genotype in bladder cancer cases was higher than in controls; 114 of 201(56.7%) vs. 62 of 146(42.5%). Men with CYP2E1(RsaI) c1/c1 genotype had increased risk of development of bladder cancer compared to men with at least one c2 allele(OR=1.7, 95% CI=1.1-2.7). The bladder cancer risk increased as the number of c1 allele increased(p for trend=0.005). The risk increased as the amount of smoking increased(p for trend=0.009). When data were analyzed for the interaction between smoking and CYP2E1 genetic polymorphisms, smokers with c1/c1 genotype have 2.5 greater risk in development of bladder cancer(95% CI=1.0-6.2) compared to nonsmokers with c2 allele(p for interaction=0.008). Our findings suggest that the interaction between genetic polymorphisms of CYP 2E1 (RsaI, c1/c1) and smoking may play an important role for development of bladder cancer among Koreans.; Summary

Glutathione S-transferase(GST) M1 and T1 Genetic Polymorphism in Benign Breast Disorders of Korean Women.: Sue Kyung Park, Mina Ha, Sook Un Kim, Daehee Kang, Keun Young Yoo; Korean J Epidemiol. 2000;22(1):52-58.

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Abstract PDF: Abstract
PURPOSE
A hospital-based case-control study was conducted to evaluate the role of glutathione-S-transferase(GST)M1 and GSTT1 genetic polymorphism for developing benign breast disorders(fibrocystic diseases and fibroadenoma) in Korea. MATERIALS AND METHODS: Histologically confirmed incident cases of benign breast disorder(n=56) were selected from inpatients at the Department of General Surgery, Seoul National University Hospital since 1994. Women with free of self-reporting past history of any malignancies were regarded as controls who were selected from the inpatients at the same department at three hospitals during 1994 to 1998(n=180). Information on life-styles including reproductive factors were obtained by direct interview using questionnaire. Age and menopausal status were matched and 51 cases and 102 controls were finally selected. Odds ratio and 95% confidence interval were estimated by multiple logistic regression after adjusting for age, education, body mass index, smoking history, drinking history, menstrual regularity, age at menarch, age at first pregnancy, frequency of fullterm pregnancy, breast feeding history, duration of breast feeding, and family history of breast cancer.
RESULTS
GSTM1-null type showed no significance related to the risk of benign breast disorder(adjusted OR=0.8, 95% CI=0.38-1.83) and GSTT1-null type was also not significant(adjusted OR=1.4, 95% CI=0.63-3.29). Increasing tendency of disease risk by the number of GSTs null type was not observed (ptrend>0.1) after adjusting for all other variables.
DISCUSSIONS
Further investigation with larger sample size should be needed to provide more concrete information on the role of GST genetic polymorphism in benign breast cancer and a lots of studies relation in normal level of GST genetic polymorphism in general population should be performed.; Summary

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