GENETIC AND ENVIRONMENTAL DETERMINANTS OF MAMMOGRAPHIC DENSITY: A TWINS AND SISTERS STUDY

乳腺癌是澳大利亚妇女早期死亡和残疾的主要原因。乳房密度是女性乳房的一个特征，可以通过乳房X光检查（如乳房筛查）来测量，许多大型研究表明，乳房密度是乳腺癌的一个主要风险因素。这是一个无法通过乳房检查测量的特征，但可以通过乳房扫描很好地测量。虽然乳腺密度在绝经期和绝经后随着年龄的增长而下降，但同一年龄段的女性乳腺密度差异很大。确定相同年龄的女性乳房密度差异如此之大的原因将有助于更好地了解乳腺癌的原因，并对预防产生影响。我们与加拿大多伦多的诺曼·博伊德博士合作进行了一项大型双胞胎研究，研究表明，乳房密度的大部分变化可能是由于尚未发现的遗传因素。所涉及的基因不是目前已知的乳腺癌易感基因BRCA1和BRCA2。我们还发现，生活方式因素，如孩子的数量，也会影响乳房密度。在这个更大的双胞胎和姐妹对的研究中，我们将测试特定的激素基因，如与雌激素和孕激素有关的基因，是否可以解释部分遗传效应。我们还将通过比较相同或相似年龄的双胞胎和姐妹，更密切地研究环境和生活方式因素对乳房密度的影响，特别是它们的影响如何与我们确定的任何遗传因素相互作用。通过研究患有子宫内膜异位症的女性，我们将能够发现她们患乳腺癌的风险是否会增加，这反映在她们的乳房密度上。通过收集所有参与者的血液样本，我们将建立一个庞大的资源，用于未来的基因组扫描研究，试图发现影响乳腺密度的新基因，并暗示乳腺癌的风险。

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.