Dataset Information

Interaction between alcohol consumption and methylenetetrahydrofolate reductase polymorphisms in thyroid cancer risk: National Cancer Center cohort in Korea.

ABSTRACT: The effect of alcohol intake on thyroid cancer is unestablished, and its interaction effects with genetic susceptibility are unclear. In this case-control study, the relationship among alcohol intake, the methylenetetrahydrofolate reductase (MTHFR) gene, and thyroid cancer risk has been evaluated. In total, 642 cases and 642 controls of Korean origin were included, and the genetic variants C677T and A1298C of the MTHFR gene were analysed. The interactions between alcohol-consumption behaviour and genetic variants were analysed with a likelihood ratio test, wherein a multiplicative interaction term was added to a logistic regression model. There was an independent association between the C677T polymorphism and thyroid cancer risk but not for drinking history. For C677T C/C homozygotes, individuals with a history of alcohol consumption showed a protective OR (95% CI) of 0.42 (0.15-1.13) when never drinkers were used as the reference. However, this protective association was not observed among individuals with a T+ allele with an OR (95% CI) of 1.27 (0.89-1.82), showing different directions for the association between genotypes with a significant interaction (Pinteraction?=?0.009). Based on the genetic characteristics of individuals included, an interaction between alcohol intake and MTHFR C677T may modify the risk of thyroid cancer.

SUBMITTER: Yang S

PROVIDER: S-EPMC5840348 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Interaction between alcohol consumption and methylenetetrahydrofolate reductase polymorphisms in thyroid cancer risk: National Cancer Center cohort in Korea.

Yang Sarah S Lee Jeonghee J Park Yoon Y Lee Eun Kyung EK Hwangbo Yul Y Ryu Junsun J Sung Joohon J Kim Jeongseon J

Scientific reports 20180306 1

The effect of alcohol intake on thyroid cancer is unestablished, and its interaction effects with genetic susceptibility are unclear. In this case-control study, the relationship among alcohol intake, the methylenetetrahydrofolate reductase (MTHFR) gene, and thyroid cancer risk has been evaluated. In total, 642 cases and 642 controls of Korean origin were included, and the genetic variants C677T and A1298C of the MTHFR gene were analysed. The interactions between alcohol-consumption behaviour an ...[more]

PMID: 29511243

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Project description:BackgroundCigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between MTHFR polymorphisms and lung cancer risk.MethodsWe evaluated the role of the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI).ResultsThe TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P < 0.01) while the A1298C polymorphism was not associated with lung cancer risk. The minor alleles of both polymorphisms behaved in a recessive fashion. The highest risks were seen for 677TT-carriers with a history of smoking or excessive drinking (OR = 6.16, 95% CI = 3.48 - 10.9 for smoking; OR = 3.09, 95% CI = 1.64 - 5.81 for drinking) compared with C-carriers without a history of smoking or excessive drinking, but no interactions were seen. The 1298CC genotype was only associated with increased risk among non-smokers (P < 0.05), and smoking was only associated with increased risks among 1298A-carriers (P < 0.01), but no significant interaction was seen. There was a synergistic interaction between the A1298C polymorphism and drinking (P < 0.05). The highest risk was seen for the CC-carriers with excessive drinking (OR = 7.24, 95% CI = 1.89 - 27.7) compared with the A-carriers without excessive drinking).ConclusionsThe C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk, a significant interaction with drinking was observed. Future studies incorporating data on folate intake may undoubtedly lead to a more thorough understanding of the role of the MTHFR polymorphisms in lung cancer development.

Project description:What is already known about this subject* Numerous clinical studies, including a few prospective ones, have reported conflicting results on the impact of gene polymorphisms related to fluorouracil (FU) and oxaliplatin pharmacodynamics.What this study adds* This prospective study is the first to report that clinical response to FOLFOX is significantly related to methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (677C-->T and 1298A-->C), with a response rate of 37, 53, 63 and 80% in patients harbouring no, one, two or three favourable MTHFR alleles, respectively. * Only polymorphisms of genes related to oxaliplatin pharmacodynamics (GSTpi 105Ile-->Val and XPD 751Ly-->Gln) influenced progression-free survival. * These results corroborate the observation that response was related to the cumulative FU dose, whereas progression-free survival was related to the cumulative oxaliplatin dose.AimsTo test prospectively the predictive value of germinal gene polymorphisms related to fluorouracil (FU) and oxaliplatin (Oxa) pharmacodynamics on toxicity and responsiveness of colorectal cancer (CRC) patients receiving FOLFOX therapy.MethodsAdvanced CRC patients (n= 117) receiving FOLFOX 7 therapy were enrolled. Gene polymorphisms relevant for FU [thymidylate synthase (TYMS, 28 bp repeats including the G-->C mutation + 6 bp deletion in 3'UTR), methylenetetrahydrofolate reductase (MTHFR, 677C-->T, 1298A-->C), dihydropyrimidine deshydrogenase (IVS14+1G-->A) and Oxa: glutathione S-transferase (GST) pi (105Ile-->Val, 114Ala-->Val), excision repair cross-complementing group 1 (ERCC1) (118AAT-->AAC), ERCC2 (XPD, 751Lys-->Gln) and XRCC1 (399Arg-->Gln)] were determined (blood mononuclear cells).ResultsNone of the genotypes was predictive of toxicity. Response rate (54.7% complete response + partial response) was related to FU pharmacogenetics, with both 677C-->T (P= 0.042) and 1298A-->C (P= 0.004) MTHFR genotypes linked to clinical response. Importantly, the score of favourable MTHFR alleles (677T and 1298C) was positively linked to response, with response rates of 37.1, 53.3, 62.5 and 80.0% in patients bearing no, one, two or three favourable alleles, respectively (P= 0.040). Polymorphisms of genes related to Oxa pharmacodynamics showed an influence on progression-free survival, with a better outcome in patients bearing GSTpi 105 Val/Val genotype or XPD 751Lys-containing genotype (P= 0.054).ConclusionsThese results show that response to FOLFOX therapy in CRC patients may be driven by MTHFR germinal polymorphisms.

Dataset Information

Interaction between alcohol consumption and methylenetetrahydrofolate reductase polymorphisms in thyroid cancer risk: National Cancer Center cohort in Korea.

Publications

Interaction between alcohol consumption and methylenetetrahydrofolate reductase polymorphisms in thyroid cancer risk: National Cancer Center cohort in Korea.

Similar Datasets

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