Clinical trial NCT02266641: Parental One-carbon Folate and Choline Nutrition Modulates Risk of Off-spring Cancer Development: Human Cohort Study
Official title: Parental One-carbon Folate and Choline Nutrition Modulates Risk of Off-spring Cancer Development: Human Cohort Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Off-spring Cancer Risk
Keywords: one-carbon metabolism
folate
choline
DNA methylation
imprint marker
cancer risks
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2014-10-17
Enrollment: 118
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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

Primary outcomes:
measure: Assessment of maternal one-carbon nutrient (folate, choline, betaine, Vitamine B12) intake at the first trimester visit of pregnancy
timeFrame: 7-10 weeks
measure: Assessment of maternal one-carbon nutrient (folate, choline, betaine, Vitamine B12) intake at the second trimester of pregnancy
timeFrame: 20-28 weeks
measure: Assessment of maternal one-carbon nutrient (folate, choline, betaine, Vitamine B12) intake at the third trimester of pregnancy
timeFrame: 36-37 weeks
Secondary outcomes:
measure: Measure maternal blood and urine biochemistry (folate, choline, betaine, homocysteine, Vitamine B2, Vitamine B6, Vitamine B12, etc.)
timeFrame: 7-10 weeks
measure: 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.)
timeFrame: 7-10 weeks
measure: Measure maternal blood and urine biochemistry (folate, choline, betaine, homocysteine, Vitamine B2, Vitamine B6, Vitamine B12, etc.)
timeFrame: 24-28 weeks
measure: 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.)
timeFrame: 24-28 weeks
measure: Measure maternal blood, cord blood and urine biochemistry (folate, choline, betaine, homocysteine, Vitamine B2, Vitamine B6, Vitamine B12, etc.)
timeFrame: 37-40 weeks
measure: Measure maternal and cord blood and placenta tissues MTHFR C677T genotypes
timeFrame: 37-40 weeks
measure: 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.)
timeFrame: 37-40 weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Chien-Nan Lee
role: PRINCIPAL_INVESTIGATOR
affiliation: Hueishin women and children clinic
name: Kuang-Ta Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital
name: Chin-Pao Cheng
role: PRINCIPAL_INVESTIGATOR
affiliation: Fu Jen Catholic University
name: Rwei-Fen S. Huang
role: PRINCIPAL_INVESTIGATOR
References: