Parental One-carbon Folate and Choline Nutrition Modulates Risk of Off-spring Cancer Development: Human Cohort Study

Study Overview
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Brief Summary
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Parental one-carbon nutrient intake (folic acid and choline) and the genetic polymorphisms of one-carbon metabolic enzyme were interact with regulating embryonic one-carbon metabolic environment, affect fetal DNA and RNA biosynthesis and methyl modification of the genome molecule, to promote the individual nutrient growth factor of growth and development. Inadequate maternal one-carbon nutrient intake combined with genetic polymorphisms of one-carbon enzymatic mutation, causing one-carbon malnutrition, change fetal methyl metabolic nutrition environment. It not only leads to fetal growth mutation - such as folate and choline deficiency, increasing the risk of fetal neural tube defect but also induce abnormal modifying of fetuses's post-genomic methylation markers, may alter imprinted genes function of progenitors, recompile threshold sensitivity or domain in regulation of metabolic reactions of offspring, resulting in long-lasting effect, increasing the risk of chronic diseases of offspring such as cancer. According to the National Nutrition Survey results show that a considerable proportion of the Taiwanese people had poor one-carbon nutritional status. 48% of women intake 66% below the recommended intake reference value of folate. Whether inadequate parental one-carbon nutrients intake combined with genetic polymorphisms of one-carbon enzymatic mutation will cause one-carbon malnutrition of fetus, affecting fetal growth and modifying the risk of cancer development relationship of offspring. It is due to the lack of local ethnic data and empirical scientific reference at home and abroad, so it can not plan an effective maternal and children nutrient education and prevention strategies about methyl nutrition for early cancer prevention for Taiwanese. Therefore, indigenous people is the intended population of study in this project, screening of healthy pregnant women with high risk factor for cancer and obese pregnant women, and detection of one-carbon nutrient intake and biochemical assessment of the nutritional status of the study group. Supplying nutrition education intervention or multivitamin supplement to improve the poor nutritional status of persons. Using related DNA methylation imprint marker about offspring growth and modifying development of cancer as assessment, this project explores the appropriate one-carbon nutrient intake in parents and children and the assessments in regulation of growth and reducing the cancer-related risk.

Official Title
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Parental One-carbon Folate and Choline Nutrition Modulates Risk of Off-spring Cancer Development: Human Cohort Study

Conditions
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Off-spring Cancer Risk

Intervention / Treatment
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* Behavioral: nutrition counseling
* Dietary Supplement: multivitamin supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy pregnant women aged 21-40 years with first and single fetal pregnancy Healthy pregnant women aged 21-40 years with first and single fetal pregnancy and lineal relative had diabetes Healthy pregnant women aged 21-40 years with first and single fetal pregnancy and lineal relative had cancer Healthy pregnant women, who are overweight/obesity (pre-pregnancy BMI≧24 kg/m2) or her lineal relative with overweight/obesity, aged 21-40 years with first and single fetal pregnancy. Exclusion Criteria: Pregnant women who had heart disease, kidney disease, cancer or accepting medical treatment

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: healthy pregnant women<br>Supply nutrition counseling and multivitamin supplement to people with poor nutritional status | Behavioral: nutrition counseling<br>* Pregnancy diet (include one-carbon nutrients)<br>Dietary Supplement: multivitamin supplement<br> <br> |
| Experimental: healthy pregnant women's lineal relative with cancer<br>Supply nutrition counseling and multivitamin supplement to people with poor nutritional status | Behavioral: nutrition counseling<br>* Pregnancy diet (include one-carbon nutrients)<br>Dietary Supplement: multivitamin supplement<br> <br> |
| Experimental: pregnant women or lineal relative with overweight/obesity<br>Supply nutrition counseling and multivitamin supplement to people with poor nutritional status | Behavioral: nutrition counseling<br>* Pregnancy diet (include one-carbon nutrients)<br>Dietary Supplement: multivitamin supplement<br> <br> |
| No Intervention: healthy pregnant women's lineal relative with diabetes<br>Supply nutrition counseling and multivitamin supplement to people with poor nutritional status | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of maternal one-carbon nutrient (folate, choline, betaine, Vitamine B12) intake at the first trimester visit of pregnancy | Using semiquantitative food frequency questionnaires (FFQ) to calculate dietary intake of one-carbon nutrient | 7-10 weeks | 
| Assessment of maternal one-carbon nutrient (folate, choline, betaine, Vitamine B12) intake at the second trimester of pregnancy | Using 24 hours dietary recall and dietary record to calculate dietary intake of one-carbon nutrient | 20-28 weeks | 
| Assessment of maternal one-carbon nutrient (folate, choline, betaine, Vitamine B12) intake at the third trimester of pregnancy | Using 24 hours dietary recall and dietary record to calculate dietary intake of one-carbon nutrient | 36-37 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure maternal blood and urine biochemistry (folate, choline, betaine, homocysteine, Vitamine B2, Vitamine B6, Vitamine B12, etc.) |  | 7-10 weeks | 
| Measure maternal blood imprinted genes (sonic hedgehog, insulin-like growth factor 2, long interspersed nuclear element 1, etc.) DNA methylation status, DNA 8-Hydroxydeoxyguanosine (8-OHdG) and inflammatory markers (TNF-α, NF-κB, Interleukin, etc.) |  | 7-10 weeks | 
| Measure maternal blood and urine biochemistry (folate, choline, betaine, homocysteine, Vitamine B2, Vitamine B6, Vitamine B12, etc.) |  | 24-28 weeks | 
| Measure maternal blood imprinted genes (sonic hedgehog, insulin-like growth factor 2, long interspersed nuclear element 1, etc.) DNA methylation status, DNA 8-Hydroxydeoxyguanosine and inflammatory markers (TNF-α, NF-κB, Interleukin, etc.) |  | 24-28 weeks | 
| Measure maternal blood, cord blood and urine biochemistry (folate, choline, betaine, homocysteine, Vitamine B2, Vitamine B6, Vitamine B12, etc.) |  | 37-40 weeks | 
| Measure maternal and cord blood and placenta tissues MTHFR C677T genotypes |  | 37-40 weeks | 
| Measure maternal blood imprinted genes (sonic hedgehog, insulin-like growth factor 2, long interspersed nuclear element 1, etc.) DNA methylation status, DNA 8-Hydroxydeoxyguanosine (8-OHdG) and inflammatory markers (TNF-α, NF-κB, Interleukin, etc.) |  | 37-40 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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one-carbon metabolism, folate, choline, DNA methylation, imprint marker, cancer risks