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

NCT02266641 | Completed

• 1 other identifier: 201401034RINB
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Off-spring Cancer Risk

Keywords

one-carbon metabolism; folate; choline; DNA methylation; imprint marker; cancer risks

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• 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

Study Arms (4)

healthy pregnant women

ACTIVE COMPARATOR

Supply nutrition counseling and multivitamin supplement to people with poor nutritional status

Behavioral: nutrition counseling; Dietary Supplement: multivitamin supplement

healthy pregnant women's lineal relative with cancer

EXPERIMENTAL

Supply nutrition counseling and multivitamin supplement to people with poor nutritional status

Behavioral: nutrition counseling; Dietary Supplement: multivitamin supplement

pregnant women or lineal relative with overweight/obesity

EXPERIMENTAL

Supply nutrition counseling and multivitamin supplement to people with poor nutritional status

Behavioral: nutrition counseling; Dietary Supplement: multivitamin supplement

healthy pregnant women's lineal relative with diabetes

NO INTERVENTION

Supply nutrition counseling and multivitamin supplement to people with poor nutritional status

Interventions

nutrition counseling BEHAVIORAL

Pregnancy diet (include one-carbon nutrients)

healthy pregnant women; healthy pregnant women's lineal relative with cancer; pregnant women or lineal relative with overweight/obesity

multivitamin supplement DIETARY_SUPPLEMENT

healthy pregnant women; healthy pregnant women's lineal relative with cancer; pregnant women or lineal relative with overweight/obesity

Eligibility Criteria

• Age: 21 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Pregnant women who had heart disease, kidney disease, cancer or accepting medical treatment

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2014
• First Posted: October 17, 2014
• Study Start: October 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 1, 2018

Record last verified: 2017-05

Locations

TW (1)