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Environmental And Genetic Factors In Childhood Acute Lymphoblastic Leukaemia: A Case-control Study.
Funder
National Health and Medical Research Council
Funding Amount
$1,788,500.00
Summary
In most countries, acute lymphoblastic leukaemia is the commonest cancer in children. One in 2000 children will develop this disease before their 15th birthday. New methods of treatment introduced over the last 30 years have resulted in cure for many children. However, one third of children diagnosed with this type of leukaemia still die and, even in those whose lives are saved, cure is achieved at a significant cost to the child, the family and the community. Greater understanding of the develo ....In most countries, acute lymphoblastic leukaemia is the commonest cancer in children. One in 2000 children will develop this disease before their 15th birthday. New methods of treatment introduced over the last 30 years have resulted in cure for many children. However, one third of children diagnosed with this type of leukaemia still die and, even in those whose lives are saved, cure is achieved at a significant cost to the child, the family and the community. Greater understanding of the development of childhood leukaemia may lead to preventive measures. Most children with this type of leukaemia are very young, suggesting that factors to which parents are exposed may affect future children. For this reason, as well as investigating the health and lifestyle of the child, it is essential to study the parents. Recent research suggests an association between the mother's intake of folate during pregnancy and her child's risk of developing the most common type of childhood leukaemia. It is also apparent that genetic differences result in varying abilities to deal with toxins, which may alter the risk of developing some cancers. Diet and lifestyle probably also affect this risk. These observations and interactions need to be examined in greater detail. In this large Australia-wide study specific genes will, for the first time, be examined and analysed in conjunction with rigorous assessment of exposures thought to be related to the development of childhood leukaemia. Results obtained from children with leukaemia and their parents will be compared with those from healthy children and their parents. This study is unique in its attempt to assess gene-environment interactions in Australian children and their parents. It will clarify the role of folate and other potential environmental agents in the development of childhood leukaemia and examine gene variations that may affect cancer risk.Read moreRead less
Functional And Epigenetic Consequences Of Maternal Folate Deficiency, Supplementation And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$545,183.00
Summary
Growing slowly before birth or being born early and premature are very common. Both conditions greatly increase the risk of illness or death around birth and of the infant developing major conditions such as diabetes and cardiovascular disease in later life. Despite their importance, we understand little of what causes fetal growth failure or prematurity or why they influence an individual's health throughout life. Recent findings suggest that low levels of folate in the mother, due to either di ....Growing slowly before birth or being born early and premature are very common. Both conditions greatly increase the risk of illness or death around birth and of the infant developing major conditions such as diabetes and cardiovascular disease in later life. Despite their importance, we understand little of what causes fetal growth failure or prematurity or why they influence an individual's health throughout life. Recent findings suggest that low levels of folate in the mother, due to either dietary or genetic factors, may be involved in their origins and their long-term outcomes. Folate is a nutrient required regularly in small amounts for growth and maintenance of health. Folate supplementation in women is currently recommended before and in early pregnancy, but may have a role throughout the whole of pregnancy in promoting growth and health of the infant. Using experimental models, this project will determine if too little or too much maternal folate modifies the genetic code of the infant (called epigenetic changes), which leads to later metabolic disease and high blood pressure. These epigenetic changes are mild and subtle chemical modifications of DNA that persist in the cells of the infant altering their function. The efficacy of maternal folate supplementation in improving these outcomes for the small baby will also be tested in the models. Finally, the effect of folate status in the normal and small human infant on the epigenetic state of their placenta, cord blood white blood cells and mucous cells of the mouth will be tested. These outcomes will enable the design and testing of interventions with folate and related nutrients in the mother to improve the health of their babies before birth and subsequently throughout their lives. Because these pregnancy complications of being born small or early are common and account for much of the diabetes that occurs in later life, the health benefits from development of effective interventions may be large.Read moreRead less
An Investigation Into The Molecular Basis Of MAIT Cell Recognition Of Vitamin B Based Metabolites
Funder
National Health and Medical Research Council
Funding Amount
$883,762.00
Summary
Mucosal associated invariant T cells (MAIT cells) are an abundant T-cell population in humans, that is found mostly in the gastrointestinal mucosa. We have recently shown that MAIT cells can be activated by metabolites of vitamin B. This proposal will investigate how the MAIT cells "see" vitamin B metabolites. This research will pave the way for novel therapeutics that can modulate MAIT cell activity.
Epigenetic Programming Of Immune Development In Utero: Role Of The Maternal Environment In The Allergy Epidemic
Funder
National Health and Medical Research Council
Funding Amount
$764,463.00
Summary
This study will provide new insights into the development of allergic disease. Specifically, we will explore the hypothesis that allergic disease and other disorders or immune dysregulation occur as a result of gene-environmental interactions in early life, and that these events begin in pregnancy when the developing fetus is still developing and most susceptible to these effects.
A Randomised Controlled Trial Of High Dose Folic Acid To Slow The Progression Of Atheroma In Renal Failure (194246)
Funder
National Health and Medical Research Council
Funding Amount
$326,980.00
Summary
The Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is examining the effect of high dose folic acid supplementation on the development of desease of the heart and blood vessels in people with kidney failure. Subjects in the study take 15mg folic acid daily or a dummy tablet for 3 to 5 years. Folic acid is known to reduce the levels of a substance called homocysteine which is elevated in people with kidney disease. Homocysteine has been associated with disease of the heart and blood ....The Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is examining the effect of high dose folic acid supplementation on the development of desease of the heart and blood vessels in people with kidney failure. Subjects in the study take 15mg folic acid daily or a dummy tablet for 3 to 5 years. Folic acid is known to reduce the levels of a substance called homocysteine which is elevated in people with kidney disease. Homocysteine has been associated with disease of the heart and blood vessels and these diseases occur very commonly in people who also have kidney failure. I t is hoped that by using folic acid to reduce the levels of homocysteine, we can reduced the amounbt of heart and blood vessel disease in people with kidney failure.Read moreRead less
VITATOPS Study - A Randomised, Double-blind, Placebo-controlled Trial Of Vitamins To Prevent Stroke.
Funder
National Health and Medical Research Council
Funding Amount
$1,477,963.00
Summary
Stroke is one of the most important causes of death and long-term disability in developed countries. Hardening of the arteries (atherosclerosis) is the major cause of stroke and heart attacks. High blood pressure, high blood concentrations of cholesterol, cigarette smoking and diabetes accelerate the formation of atherosclerosis, but they do not account for all strokes and heart attacks caused by atherosclerosis. There is now increasing evidence that high blood concentrations of homocysteine, a ....Stroke is one of the most important causes of death and long-term disability in developed countries. Hardening of the arteries (atherosclerosis) is the major cause of stroke and heart attacks. High blood pressure, high blood concentrations of cholesterol, cigarette smoking and diabetes accelerate the formation of atherosclerosis, but they do not account for all strokes and heart attacks caused by atherosclerosis. There is now increasing evidence that high blood concentrations of homocysteine, a normal protein in the blood, are another major causal risk factor for atherosclerosis (and stroke and heart attacks). Furthermore, blood concentrations of homocysteine can be lowered by about one quarter with simple, safe and inexpensive multivitamin therapy (folic acid, vitamin B12, and vitamin B6). However, despite the potentially massive public health benefits of such a strategy, it remains to be demonstrated in properly designed clinical trials that lowering homocysteine levels in the blood actually prevents stroke and heart attack. The VITATOPS trial is the only ongoing randomised, double-blind, placebo-controlled trial in the world which aims to determine whether multivitamin therapy (folic acid 2 mg, vitamin B12 0.5 mg, and vitamin B6 25 mg) prevents recurrent stroke and heart attacks in patients who have suffered a recent stroke.Read moreRead less
VITATOPS Study - A Randomised, Double-blind, Placebo-controlled Trial Of Vitamins To Prevent Stroke.
Funder
National Health and Medical Research Council
Funding Amount
$470,887.00
Summary
The VITAmins To Prevent Stroke (VITATOPS) trial is the only ongoing randomised, double-blind, placebo-controlled trial in the world which aims to determine whether multivitamin therapy (folic acid 2 mg, vitamin B12 0.5 mg, and vitamin B6 25 mg) prevents recurrent stroke and heart attacks in patients who have suffered a recent stroke. To date more than 7,500 patients have been randomised. Ongoing support is requested to complete the follow-up of 8,000 patients by middle of 2009.