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
A Prospective Study Of The Effects Of Early Life Growth On Adult Mammographic Density
Funder
National Health and Medical Research Council
Funding Amount
$460,517.00
Summary
It is now well-known that a woman's breast density, as measured by a breast scan, is a predictor of her future risk of breast cancer. It is also known that women who are heavier as babies and grow rapidly before age 7 are more likely to develop breast cancer in adult life. The effects were strongest in women who had early puberty. It has been suggested that there are critical points in early life growth that contribute to higher breast density in middle-age. Population-based surveys with early l ....It is now well-known that a woman's breast density, as measured by a breast scan, is a predictor of her future risk of breast cancer. It is also known that women who are heavier as babies and grow rapidly before age 7 are more likely to develop breast cancer in adult life. The effects were strongest in women who had early puberty. It has been suggested that there are critical points in early life growth that contribute to higher breast density in middle-age. Population-based surveys with early life growth data on large numbers of women that span birth to adulthood are necessary to estimate accurately the association between early life growth and breast density in middle age. Few such studies exist; Tasmanian Asthma Study is one of them. In 1968, all 4,194 female Tasmanian school children born in 1961 were surveyed and height and weight measured. Subsequently, weight and height measurements were carried out on samples of this cohort. We are currently conducting the 37-year follow-up of the TAS and to date have traced 87% and achieved a response rate of 77% (2,850) for a postal survey. This included self-reported weight and height measurements and detailed information reproductive history and the use of hormones. Weight, height and waist to hip ratio are currently measured on 600 of these respondents. We have access to school medical records of the full cohort, which have weight and height data measured at school medical inspections throughout school years, and maternal records so far for half of the total cohort, which have information on birth weight and length, and period of gestation. Hence, TAS now provides an ideal opportunity, unique within Australia, to investigate prospectively the association between early life growth and mammographic density in middle-age women. We will measure breast density in these women now they are in their late 40s, using the Australian Mammographic Density Research Facility at The University of Melbourne.Read moreRead less
Apportioning Deficits In Bone Size And Density In Women With Fractures To Growth Or Ageing By Studies In Their Daughters
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Women fracture their bones because the bones are small and break easily and because the bones are thin or low in denseness (very porous like a honey comb). This study is aimed at identifying why women with fractures have small bones and why the bones are so porous. They may have these problems because they lost a lot of bone as they get older or because growth was abnormal so the size of the bone didn't reach its potential size or because the denseness of the bones didn't develop properly. The s ....Women fracture their bones because the bones are small and break easily and because the bones are thin or low in denseness (very porous like a honey comb). This study is aimed at identifying why women with fractures have small bones and why the bones are so porous. They may have these problems because they lost a lot of bone as they get older or because growth was abnormal so the size of the bone didn't reach its potential size or because the denseness of the bones didn't develop properly. The study will be carried out in women with spine or hip fractures and their daughters. All participants will have bone densitometry, provide a 24 hour urine sample and a fasting blood sample of 20 ml whole blood. Informed consent will be obtained from all participants. The bone density scan is associated with radiation exposure of about 4 mSv, about one tenth of a chest x ray, temporary bruising may follow taking blood. If we can understand the different ways osteoporosis can occur we can then start to devise specific treatments tailored to the individual. Also if we can identify the causes of small bones and bone thinness during growth it may be possible to correct some of these causes before the reduced growth and reduced building of bone occurs. We might also prevent the thinning of bone by identifying and removing causes of bone thinning.Read moreRead less
Prediction Of Adverse Outcomes Following A Fragility Fracture
Funder
National Health and Medical Research Council
Funding Amount
$148,426.00
Summary
Individuals with an existing fracture are at increased risk of adverse outcomes such as re-fracture and premature mortality, but it is not clear why. We propose to evaluate risk factors, and prognostic models, for predicting the risk of adverse outcomes. We also propose to develop a quantitative risk-benefit framework for evaluating the clinical utility of such prognostic models and help ensure that therapies appropriately address real-life experience of osteoporotic patients.