GENETIC AND ENVIRONMENTAL DETERMINANTS OF MAMMOGRAPHIC DENSITY: A TWINS AND SISTERS STUDY
Funder
National Health and Medical Research Council
Funding Amount
$703,100.00
Summary
Breast cancer is a major cause of early death and disability in Australian women. Breast density, a characteristic of women's breast that can be mesured by mammograms such as those conducted by BreastScreen, has been shown by a number of large studies to be a major risk factor for breast cancer. It is a characteristic that cannot be measured by breast examination, but is very well measured by a breast scan. Although breast density decreases with age at and after menopause, there is a large diffe ....Breast cancer is a major cause of early death and disability in Australian women. Breast density, a characteristic of women's breast that can be mesured by mammograms such as those conducted by BreastScreen, has been shown by a number of large studies to be a major risk factor for breast cancer. It is a characteristic that cannot be measured by breast examination, but is very well measured by a breast scan. Although breast density decreases with age at and after menopause, there is a large difference in breast density across women of the same age. Identifying the reasons why women of the same age differ so much in breast density will lead to a better understanding of the causes of breast cancer and have implications for prevention. We have conducted a large twin study, in collaboration with Dr Norman Boyd in Toronto, Canada, that has shown that most of this large variation in breast density could be due to as yet undiscovered genetic factors. The genes involved are not BRCA1 and BRCA2, the currently known breast cancer susceptibility genes. We have also found that lifestyle factors, such as number of children, also influences breast density. In this larger study of twins and sister pairs, we shall test whether specific hormone genes, such as those involved with estrogen and progesterone, explain part of the genetic effects. We will also study more closely the effects of environmental and lifestyle factors on breast density, especially how their effects interact with those of any genetic factors we identify, by comparing twins and sister of the same or similar age. By studying women who have had endometriosis, we will be able to find out if their small increased risk of breast cancer is reflected in their breast density. By collecting a blood sample from all participants we will build a large resource that will be used for future genome scan studies, trying to discover new genes that influence breast density, and by implication, risk of breast cancer.Read moreRead less
Fine Mapping Of A Significant Linkage Region For Endometriosis
Funder
National Health and Medical Research Council
Funding Amount
$518,250.00
Summary
Endometriosis is a common disorder affecting up to 10% of women. In this condition, a special type of tissue that normally lines the inside of the womb (the 'endometrium') starts to grow outside the womb, mostly in the pelvis (lower abdomen). Common symptoms are severe pelvic pain, menstrual problems and infertility. The disease has a major impact on women's health, relationships, productivity and life choices. The mechanisms that cause endometriosis are not well understood. Genetic factors infl ....Endometriosis is a common disorder affecting up to 10% of women. In this condition, a special type of tissue that normally lines the inside of the womb (the 'endometrium') starts to grow outside the womb, mostly in the pelvis (lower abdomen). Common symptoms are severe pelvic pain, menstrual problems and infertility. The disease has a major impact on women's health, relationships, productivity and life choices. The mechanisms that cause endometriosis are not well understood. Genetic factors influence a woman's risk of developing endometriosis and finding genes and pathways leading to this disease would be a major advance. This will help design better approaches for the diagnosis, prevention and treatment of endometriosis. Since 1996, nearly 4,000 women with endometriosis plus their families have joined our genetic study. This includes around 1,000 families with two or more sisters who both have the disease. We have looked at the DNA from these sisters and found significant evidence for a gene or genes affecting endometriosis on one chromosome. No one else has linked this location with endometriosis. We are now focusing our efforts in the laboratory on this area, which contains approximately 250 genes. The aim of our new project is to study genes in the region in more detail to pinpoint the gene or genes responsible for risk of endometriosis.Read moreRead less
Fine Mapping Of The ADH Region For Alcohol Metabolism, Use And Dependence
Funder
National Health and Medical Research Council
Funding Amount
$215,690.00
Summary
It is widely known that alcohol use and alcohol dependence can cause many social problems and morbidity. We know that social and and cultural factors can affect the possibility of becoming alcohol dependent. We also know that inheritance plays a major role in the risk of becoming dependent upon alcohol. Two inherited causes or genes have already been identified as causing some people to avoid alcohol and so have less chance of becoming dependent upon it. Clues as to why this happens come from wh ....It is widely known that alcohol use and alcohol dependence can cause many social problems and morbidity. We know that social and and cultural factors can affect the possibility of becoming alcohol dependent. We also know that inheritance plays a major role in the risk of becoming dependent upon alcohol. Two inherited causes or genes have already been identified as causing some people to avoid alcohol and so have less chance of becoming dependent upon it. Clues as to why this happens come from what happens to alcohol following a drink. The body detoxifies itself of alcohol in the liver. There it is converted to very highly toxic acetaldehyde and this is normally rapidly removed by a protein called aldehyde dehydrogenase. Some people do not have a normally functioning form of this protein and cannot remove the acetaldehyde from their bodies. They suffer unpleasant side effects such as nausea, facial flushing and sickness. Consequently they learn by experience to avoid alcohol use and are less likely to develop dependence. We now know that even people with a normally inherited form of aldehyde dehydrogenase can have a lowered risk of dependence. The rate at which our livers convert alcohol to actetaldehyde is also a key factor. Those who are inherently quick at this process again learn to avoid alcohol, others are more at risk. The hypothesis will be tested with a unique set of twins who have provided us with detailed information on how quickly they detoxify alcohol and of their drinking habits for over 20 years. Collectively they will enable us to determine if there is a major genetic influence on alcohol use and dependence that is caused by inter-individual differences in a gene for alcohol metabolism. The DNA of these twins will be used to locate mutations that we predict have a common effect upon our measures of alcohol detoxification, drinking habits and risk of alcoholism.Read moreRead less