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

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.

Study Overview

• Status: Completed
• Conditions: Off-spring Cancer Risk
• Intervention / Treatment: Behavioral: nutrition counseling; Dietary supplement: multivitamin supplement

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Healthy pregnant women aged 21-40 years with first and single fetal pregnancy
2. Healthy pregnant women aged 21-40 years with first and single fetal pregnancy and lineal relative had diabetes
3. Healthy pregnant women aged 21-40 years with first and single fetal pregnancy and lineal relative had cancer
4. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chien-Nan Lee, National Taiwan University Hospital; Principal Investigator: Kuang-Ta Huang, Hueishin women and children clinic; Principal Investigator: Chin-Pao Cheng, National Taiwan University Hospital; Principal Investigator: Rwei-Fen S. Huang, Fu Jen Catholic University

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: October 13, 2014
• First Submitted That Met QC Criteria: October 13, 2014
• First Posted (Estimate): October 17, 2014

Study Record Updates

• Last Update Posted (Actual): February 1, 2018
• Last Update Submitted That Met QC Criteria: January 30, 2018
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: DNA methylation; folate; one-carbon metabolism; choline; imprint marker; cancer risks
• Other Study ID Numbers: 201401034RINB