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A Retrospective Cross-Sectional Cohort Trial Assessing the Prevalence of MTHFR Polymorphisms and the Influence of Diet on Platinum Resistance in Ovarian Cancer Patients
Journal article   Open access   Peer reviewed

A Retrospective Cross-Sectional Cohort Trial Assessing the Prevalence of MTHFR Polymorphisms and the Influence of Diet on Platinum Resistance in Ovarian Cancer Patients

Caitlin Phillips-Chavez, Jermaine Coward, Michael Watson and Janet Schloss
Cancers, Vol.13(20), 5215
18/10/2021
DOI: https://doi.org/10.3390/cancers13205215
PMID: 34680361
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A Retrospective Cross-Sectional Cohort Trial Assessing the Prevalence of MTHFR Polymorphisms and the Influence of Diet on Platinum Resistance in Ovarian Cancer Patients545.63 kBDownloadView
Published (Version of record)CC BY V4.0,  Open Access
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A retrospective cross-sectional cohort trial assessing the prevalence of MTHFR polymorphisms and the influence of diet on platinum resistance in ovarian cancer patientsView
Published (Version of record)CC BY V4.0,  Open

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Abstract

Cancer therapies Cell cycle Cell growth Data analysis Deoxyribonucleic acid--DNA Dietary intake DNA biosynthesis DNA methylation DNA repair Drug resistance Epigenetics Folic acid Gene polymorphism Genes Gynecology Heterozygotes Homocysteine Hormone replacement therapy Metabolism Methylation Methylenetetrahydrofolate reductase Nutrient status Nutrition research Ovarian cancer Pathology Patients Platinum Polymorphism Statistical analysis Survival Tumorigenesis Vitamin B Vitamin B12 Vitamin B6 Vitamins Zinc Chemotherapy Enzymes
Simple Summary Ovarian cancer (EOC) has a very poor prognosis, with a 5-year survival rate of just 43%. One of the biggest challenges is the resistance to standard chemotherapeutics. Nutrition modification is a potential adjunct that may be suitable to support cancer therapies through epigenetic modifications of DNA and biochemical pathways associated with drug response. It was retrospectively hypothesised that carrying a methylenetetrahydrofolate reductase (MTHFR) gene polymorphism may affect chemo response in EOC, and that nutrient status may further influence response to standard platinum therapy. This small pilot study of twenty-five participants provided a novel foundation for identifying that dietary intake of vitamins B12, B6 and zinc may impact platinum-drug response in EOC dependent on MTHFR genotype. Further large-scale investigations are required to verify the findings of this study.Abstract Ovarian cancer has the lowest survival rate in gynaecologic malignancies with a 5-year survival rate of 43%. Platinum resistance is one of the main drivers of ovarian cancer mortality, of which aberrant methylation has been cited as a significant contributor. Understanding the essential role of the methylenetetrahydrofolate reductase enzyme (MTHFR) on DNA synthesis and repair, and how nutrient status can vastly affect its performance, led to the investigation of MTHFR status and dietary influence on platinum response in epithelial ovarian cancer (EOC) patients. Twenty-five adult female patients who completed first-line platinum-based chemotherapy for primary ovarian cancer were selected from Icon Cancer Centres in Australia. Participants were grouped based on platinum response. A full medical and family history, food frequency questionnaire and single blood test were completed, testing for MTHFR polymorphisms, serum folate, serum and active B12 and homocysteine levels. Nineteen of twenty-five participants had an MTHFR polymorphism. Of those, 20% were compound heterozygous, 12% were heterozygous C677T (CT), 4% homozygous C677T, 12% homozygous A1298C and 28% were heterozygous A1298C (AC). Statistically significant associations were found between dietary zinc (p = 0.0086; 0.0030; 0.0189) and B12 intakes in CT genotypes (p = 0.0157; 0.0030; 0.0068) indicating that zinc or vitamin B12 intakes below RDI were associated with this genotype. There were strong associations of vitamin B6 intakes in AC genotypes (p = 0.0597; 0.0547; 0.0610), and dietary folate in compound heterozygotes with sensitive and partially sensitive disease (p = 0.0627; 0.0510). There were also significant associations between serum folate (p = 0.0478) and dietary B12 (p = 0.0350) intakes above RDI and platinum sensitivity in wild-types as well as strong associations with homocysteine levels (p = 0.0886) and zinc intake (p = 0.0514). Associations with dietary B12 (p = 0.0514) and zinc intakes (p = 0.0731) were also strong in resistant wild types. Results indicate that dietary zinc, B12 and B6 intakes may be associated with platinum sensitivity dependent on MTHFR genotype. These results require further research to clarify the dosages necessary to elicit a response; however, they provide a novel foundation for acknowledging the role of diet on treatment response in EOC.

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