Characterize rs70991108 Polymorphism of DHFR GeneNCT03319979
DHFR 19 bp Deletion Polymorphism and Folic Acid Utilization
An observational study of Characterize rs70991108 Polymorphism of DHFR Gene, run by Tufts University.
Trial summary
A genetic variation in the gene for the protein dihydrofolate reductase (DHFR) that is necessary to utilize folic acid (a synthetic form of the B vitamin folate found in supplements and fortified food), increases the risk for breast cancer in multivitamin users and, when present in mothers who used folic acid… Read more about this study
- Who is it for?
- Ages 21 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Characterize rs70991108 Polymorphism of DHFR Gene
- How many people
- 117 participants
- Where
- No sites listed yet
- Study dates
- Feb 2013to Mar 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Healthy pre-menopausal females aged 21-45 from Metro Boston area
Who may be able to join
- Adult premenopausal women aged 21-45 in general good health, non-pregnant, minimum weight of 110 pounds.
Who cannot join
- Smoking, a terminal illness, any known chronic illness, rheumatoid arthritis, heart, kidney, liver or gastrointestinal disease requiring treatment, antifolate medications, metformin use.
- More than 2 drinks a day.
- Pregnant women have different metabolism when compared to other adults hence they will not be included in the study.
- Non-English speaking subjects will be excluded since the study involves a computer based diet history questionnaire in English. The budget for this project does not include the cost of an interpreter.
About this study
A genetic variation in the gene for the protein dihydrofolate reductase (DHFR) that is necessary to utilize folic acid (a synthetic form of the B vitamin folate found in supplements and fortified food), increases the risk for breast cancer in multivitamin users and, when present in mothers who used folic acid supplements during pregnancy, increases the risk for cancer of the eye of their children. The aim of the proposed research is to understand how a common genetic variation in the gene for DHFR affects the function of this protein and the ability of the body to use folic acid.
Read the detailed description
A 19bp deletion polymorphism of intron 1 of dihydrofolate reductase (DHFR 19bpdel) increases the risk for breast cancer, and retinoblastoma of the offspring, in folic acid supplement users. Folic acid is a synthetic form of folate present in fortified foods and supplements that must be converted to tetrahydrofolate by DHFR to enter the metabolism. Individuals homozygous for DHFR 19bpdel have higher prevalence of unmetabolized folic acid in plasma and lower incorporation of folic acid into tissues. How the DHFR19bpdel (17% homozygosity in US) affects DHFR activity and folate metabolism to increase cancer risk is not understood. Studies on this topic are urgent in the light of mandatory folic acid fortification in the US and other countries. The objective of this project is to characterize the effect of DHFR 19bpdel on DHFR activity and folate pathway reactions and to determine if the effect of DHFR 19bpdel can be alleviated with folinic acid, which is a folate source that need not be converted by DHFR. The specific aims of this project are to 1] Determine expression of DHFR mRNA and protein, splicing of intron 1 and enzyme activity in white blood cells from 3 DHFR genotypes. 2] Determine the effect of DHFR 19bpdel and folic acid or folinic acid concentration on cell growth, and folate pathway reactions in white blood cells in homozygotes for DHFR 19bpdel and those who lack the polymorphism. Results of this study will guide measures to reduce this modifiable cancer risk associated with DHFR 19bpdel.
- Keywords
- Folate, DHFR
What is being measured
The primary outcome is the main question the study is designed to answer.
DHFR mRNA and protein abundance
DHFR mRNA and protein abundance determined for the 19 bp deletion genotypes
Measured: 1 year
Secondary outcomes (1)
Reactions of folate pathway
Effect of DHFR 19bp deletion on reactions of folate pathway determined in cell culture conditions
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2017
- Study startFeb 2013
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Characterize rs70991108 Polymorphism of DHFR GeneStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Ecologic or community
- Time perspective
- Cross-sectional
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ligi Paul, Ph.D., Principal investigator, Tufts University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03319979
- Sponsor's protocol ID
- ORA# 1211023
- Status last verified
- Oct 2017
- First submitted
- 20 Oct 2017
- Last updated
- 24 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DHFR 19 bp Deletion Polymorphism and Folic Acid Utilization
- ClinicalTrials.gov ID
- NCT03319979
- Acronym / sponsor ID
- ORA# 1211023
- Keywords
- Folate, DHFR
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Tufts UniversityUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 24 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A genetic variation in the gene for the protein dihydrofolate reductase (DHFR) that is necessary to utilize folic acid (a synthetic form of the B vitamin folate found in supplements and fortified food), increases the risk for breast cancer in multivitamin users and, when present in mothers who used folic acid supplements during pregnancy, increases the risk for cancer of the eye of their children. The aim of the proposed research is to understand how a common genetic variation in the gene for DHFR affects the function of this protein and the ability of the body to use folic acid.
Detailed description
A 19bp deletion polymorphism of intron 1 of dihydrofolate reductase (DHFR 19bpdel) increases the risk for breast cancer, and retinoblastoma of the offspring, in folic acid supplement users. Folic acid is a synthetic form of folate present in fortified foods and supplements that must be converted to tetrahydrofolate by DHFR to enter the metabolism. Individuals homozygous for DHFR 19bpdel have higher prevalence of unmetabolized folic acid in plasma and lower incorporation of folic acid into tissues. How the DHFR19bpdel (17% homozygosity in US) affects DHFR activity and folate metabolism to increase cancer risk is not understood. Studies on this topic are urgent in the light of mandatory folic acid fortification in the US and other countries. The objective of this project is to characterize the effect of DHFR 19bpdel on DHFR activity and folate pathway reactions and to determine if the effect of DHFR 19bpdel can be alleviated with folinic acid, which is a folate source that need not be converted by DHFR. The specific aims of this project are to 1] Determine expression of DHFR mRNA and protein, splicing of intron 1 and enzyme activity in white blood cells from 3 DHFR genotypes. 2] Determine the effect of DHFR 19bpdel and folic acid or folinic acid concentration on cell growth, and folate pathway reactions in white blood cells in homozygotes for DHFR 19bpdel and those who lack the polymorphism. Results of this study will guide measures to reduce this modifiable cancer risk associated with DHFR 19bpdel.
Study design
- Observational model
- Ecologic or community
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 21 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Healthy pre-menopausal females aged 21-45 from Metro Boston area
Key inclusion criteria (1 listed)
- Adult premenopausal women aged 21-45 in general good health, non-pregnant, minimum weight of 110 pounds.
Key exclusion criteria (4 listed)
- Smoking, a terminal illness, any known chronic illness, rheumatoid arthritis, heart, kidney, liver or gastrointestinal disease requiring treatment, antifolate medications, metformin use.
- More than 2 drinks a day.
- Pregnant women have different metabolism when compared to other adults hence they will not be included in the study.
- Non-English speaking subjects will be excluded since the study involves a computer based diet history questionnaire in English. The budget for this project does not include the cost of an interpreter.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
DHFR mRNA and protein abundance
Time frame: 1 year
DHFR mRNA and protein abundance determined for the 19 bp deletion genotypes
1 secondary outcome
Reactions of folate pathway
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2017.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ligi Paul, Ph.D. principal investigator
Tufts University
Questions about this trial
What is this clinical trial studying?
An observational study of Characterize rs70991108 Polymorphism of DHFR Gene, run by Tufts University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DHFR mRNA and protein abundance (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2017.