Rationale for the
Project
Breast cancer is a major cause of early
death in Australian women. Breast 'density', a characteristic of women's
breasts that can be measured by a mammogram, has been shown by a number of large
studies to be a major risk factor for breast cancer. It is a characteristic
that can not be measured by breast examination, but is very well measured by
a breast scan. Although breast density decreases with age 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 cause of breast
cancer and have implications for prevention. Professor John Hopper and
colleges 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. They have also found that lifestyle factors, such as
number of children, also influences breast density. In this new large study
of twins and sister pairs, we shall test whether specific 'hormone' genes,
such as 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 sisters 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 genetic studies,
trying to discover new genes that influence breast density, and by
implication, risk of breast cancer.
Scientific Aims of the
Project
The research questions we wish to address are:
1. that percent mammographic density (PMD)
tracks strongly with time in an individual across the age range 40 to 70
years
2. that specific variants in estrogen
metabolism genes are associated with PMD
3. that number of live births associated
with PMD after menopause, and the effect size increases with age; that
smoking reduces PMD before menopause but not after menopause
4. that the effects of
measured body and lifestyle factors on PMD may differ according to the
woman's genotype for one or more estrogen metabolizing genes.
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